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SLiMSuite REST Server |
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SLiMSuite SLiMFinder Server
# Output for SLiMFinder V5.2.3: Wed Dec 9 00:29:07 2015
# 1 warnings; 0 errors: see log output (below) for details.
# JobID: 15120900002
Your SLiMFinder job has finished running and outputs have been parsed.
Click on tabs to see server output. (Mouseover for description.)
The outfmt tab contains more information on the outputs.
Click here for SLiMFinder help/documentation.
Content for individual tabs can be returned using &rest=X , where X is the tab name (e.g. &rest=log ). Full output can be returned as text using &rest=full and parsed using SLiMParser: python PATH/slimparser.py restin=JOBID restout=T [password=X] [restbase=X]
JobID 15120900002 (slimfinder) Finished.
IP:129.94.133.155
No queue.
slimfinder&uniprotid=CTBP1&dismask=T&runid=CtBP1-DisMask
Run Started: 2015-12-09 00:29:07; PID=39282
Run finished: 2015-12-09 00:35:16
SLiMs and SLiMFinder
Short linear motifs (SLiMs) in proteins are functional microdomains of fundamental importance in many biological
systems. SLiMs typically consist of a 3 to 10 amino acid stretch of the primary protein sequence, of which as few
as two sites may be important for activity. SLiMFinder is a SLiM discovery program building on the principles of
the SLiMDisc software for accounting for evolutionary relationships between input proteins. This stops results
being dominated by motifs shared for reasons of history, rather than function. SLiMFinder runs in two phases:
(1) SLiMBuild constructs the motif search space based on number of defined positions, maximum length of "wildcard
spacers" and allowed amino acid ambiguities; (2) SLiMChance assesses the over-representation of all motifs,
correcting for the size of the SLiMBuild search space. This gives SLiMFinder high specificity.
Protein sequences can be masked prior to SLiMBuild. Disorder masking (using IUPred predictions) is highly
recommended. Other masking options are described in the manual and/or literature.
Running SLiMFinder
The standared REST server call for SLiMFinder is in the form:
slimfinder&uniprotid=LIST&dismask=T/F&consmask=T/F
Run with &rest=docs for program documentation and options. A plain text version is accessed with &rest=help .
&rest=OUTFMT can be used to retrieve individual parts of the output, matching the tabs in the default
( &rest=format ) output. Individual OUTFMT elements can also be parsed from the full ( &rest=full ) server output,
which is formatted as follows:
###~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~###
# OUTFMT:
... contents for OUTFMT section ...
More options are available through the SLiMFinder server: http://www.slimsuite.unsw.edu.au/servers/slimfinder.php
After running, click on the main tab to see overall SLiM predictions. If any SLiMS have been predicted, the
occ tab will have details of which proteins (and where) they occur.
If no SLiMs are returned: [1] Try altering the masking settings. (Disorder masking is recommended. Conservation
masking can sometimes help but it depend on the dataset.) [2] Try relaxing the probability cutoff. Set
[probcut=1.0]{cmd:probcut} to see the best motifs, regardless of significance. (You may also want to reduce the [topranks=X]{cmd:topranks}
setting.)
Available REST Outputs
main = Main results table of predicted SLiM patterns (if any) [ [extras=-1]{cmd:extras} ]
occ = Occurrence table showing individual SLiM occurrences in input proteins [ [extras=0]{cmd:extras} ]
upc = List of Unrelated Protein Clusters (UPC) used for evolutionary corrections [ [extras=0]{cmd:extras} ]
cloud = Predicted SLiM "cloud" output, which groups overlapping motifs [ [extras=1]{cmd:extras} ]
seqin = Input sequence data [ [extras=-1]{cmd:extras} ]
slimdb = Parsed input sequences in fasta format, used for UPC generation etc. [ [extras=0]{cmd:extras} ]
masked = Masked input sequences (masked residues marked with X ) [ [extras=1]{cmd:extras} ]
mapping = Fasta format with positions of SLiM occurrences aligned [ [extras=1]{cmd:extras} ]
motifaln = Fasta format of individual SLiM alignments (unmasked sequences) [ [extras=1]{cmd:extras} ]
maskaln = Fasta format of individual SLiM alignments (masked sequences) [ [extras=1]{cmd:extras} ]
Additional REST Outputs [extras>1]
To get additional REST outputs, set &extras=2
or &extras=3
. This may increase run times noticeably,
depending on the number of SLiMs returned.
motifs = SLiM predictions reformatted in plain motif format for CompariMotif [ [extras=2]{cmd:extras} ]
compare = Results of all-by-all CompariMotif search of predicted SLiMs [ [extras=2]{cmd:extras} ]
xgmml = SLiMs, occurrences and motif relationships in a Cytoscape-compatible network [ [extras=2]{cmd:extras} ]
dismatrix = Input sequence distance matrix [ [extras=3]{cmd:extras} ]
rank = Main table in SLiMDisc output format [ [extras=3]{cmd:extras} ]
dat.rank = Occurrence table in SLiMDisc output format [ [extras=3]{cmd:extras} ]
teiresias = Motif prediction output in TEIRESIAS format [ [extras=3]{cmd:extras} [teiresias=T]{cmd:teiresias} ]
teiresias.fasta = TEIRESIAS masked fasta output [ [extras=3]{cmd:extras} [teiresias=T]{cmd:teiresias} ]
Click here and save the page to download this output.
Dataset |
RunID |
Masking |
Build |
Chance |
RunTime |
SeqNum |
UPNum |
AANum |
MotNum |
Rank |
Sig |
Pattern |
IC |
Occ |
Support |
UP |
ExpUP |
Prob |
Cloud |
CloudSeq |
CloudUP |
slimfinder |
CtBP1-DisMask |
FreqDisComp-5-8 |
l5w2o2a3 |
Sig |
00:06:01 |
20 |
16 |
11797 |
0 |
0 |
0.1 |
- |
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Click here and save the page to download this output.
Dataset |
RunID |
Rank |
Pattern |
Sig |
Seq |
Start_Pos |
End_Pos |
Prot_Len |
Match |
Variant |
MisMatch |
Desc |
PepSeq |
PepDesign |
Click here and save the page to download this output.
#slimfinder# 20 Seq; 16 UPC; 19.049 MST; blaste=1.00e-04, blastcf=F, blastf=T
UP N MST Seqs
1 2 1.909 ATX1L_HUMAN__P0C7T5 SOBP_HUMAN__A7XYQ1
2 1 1.000 BRCA1_HUMAN__P38398
3 1 1.000 CBX4_HUMAN__O00257
4 1 1.000 CHD3_HUMAN__Q12873
5 1 1.000 COM1_HUMAN__Q99708
6 1 1.000 CTBP1_HUMAN__Q13363
7 1 1.000 CTNA1_HUMAN__P35221
8 1 1.000 HDAC2_HUMAN__Q92769
9 3 2.489 HIC1_HUMAN__Q14526 IKZF1_HUMAN__Q13422 ZN219_HUMAN__Q9P2Y4
10 1 1.000 ITF2_HUMAN__P15884
11 1 1.000 KAT2B_HUMAN__Q92831
12 2 1.651 LCORL_HUMAN__Q8N3X6 LCOR_HUMAN__Q96JN0
13 1 1.000 MDS1_HUMAN__Q13465
14 1 1.000 NOL4L_HUMAN__Q96MY1
15 1 1.000 NRIP1_HUMAN__P48552
16 1 1.000 RBBP5_HUMAN__Q15291
Click here and save the page to download this output.
>ATX1L_HUMAN__P0C7T5 RecName: Full=Ataxin-1-like; AltName: Full=Brother of ataxin-1; Short=Brother of ATXN1;
XKPVHERSQECLPPKKRDLPVTSEDMGRTTSCSTNHTPSSDASEWSRGVVVAGQSQAGARVSLGGDGAEAITXXXXXXXXXXXXXXVXXAXXXPTGLPSVVNMSPLXXXXNVASSLIQHXXIXYPPLHYAXXXSTXXXXXXXPXXXXXXXXXXXXXXXLLSPSANLATXHLPXFVPYASLLAEGATPXXQAXSPAHSFNKAPSATSPSGQLPHHSSTQPLDLAPGRMPIYYQMSRLPAGYTLHETPPAGASPVLTPQESQSALEXXXANGGQRPRERNLVRRESEALDSPNSKGEGQGLVPXXECXVDGQLFSGSQTPRVEVAAPAHRGTPDTDLEVQRVVGALASQDYRVVAAQRKEEPSPLNLSHHTPDHQGEGRGSARNPAELAEKSQARGFYPQSHQEPVKHRPLPKAMVVANGNLVPTGTDSGLLPVGSEILVASSLDVQARATFPDKEPTPPPITSSHLPSHFMKGAIIQLATGELKRVEDLQTQDFVRSAEVSGXXXIDSSTVVDXQXSXXXXXXXLHXXXXXXXSKVSIEVPPEXXXXXYGQGWSXXXXGXXXXXXXLXXXXXXXXXXXXXXXXXSLXXNSVSQASCAPPSQLGPPRERPERTVLGSRELCDSEGKSQPAGEGSRVVEPSQPESGAQACWPAPSFQRYSMQGEEARAALLRPSFIPQEVKLSIEGRSNAGK
>BRCA1_HUMAN__P38398 RecName: Full=Breast cancer type 1 susceptibility protein; EC=6.3.2.-; AltName: Full=RING finger protein 53;
XDLSALRXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXLXXXXXXXXSXXESTXFXXXXXXXXXXXXXXXXXXXXXXXXSYNFAKKENNSPEHLKDEVSIIQSMGYRNRAKRLLQSEPENPSLQETSLSVQLSNLGTVRTLRTKQRIQPQKTSVYIELGSDSSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFSETDVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSSLLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNXXHXXXXXIXXXFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKADLAVQKTPEMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESAFKTKAEPISSSISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCTELQIDSCSSSEEIKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSDTFPELKLTNAPGSFTKCSNTSELKEFVNPSLPREXKXXKLETVKVSNNAEDPKDLMLSGERVLQTERSVEXXXISLVPGTDYGTQESISLLEVSTLGKAKTEPXKCVSQCAAFXXXKGLIHGCSKDNRNDTEGFKYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSFAPFSNPGNAEEECATFSAHSGSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITAGFPVVGQKDKPVDNAKCSIKGXSRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFPIKSFVKTKCKKNLLEENFEEHSMSPEREMGNENIPSTVSTISRNNIRENVFKEASSSNINEVGSSTNEVGSSINEIGSSDENIQAELGRNRGPKLNAMLRLGVLQPEVYKQSLPGSNCKHPEIKKQEYEEVVQTVNTDFSPYLISDNLEQPMGSSHASQVCSETPDDLLDDGEIKEDTSFAENDIKESSAVFSKSVQKGELSRSPSPFTHTHLAQGYRRGAKKLESSEENLSSEDEELPCFQHLLFGKVNNIPSQSTRHSTVATECLSKNTEENLXSLKNSXXXXXNQVILAKASQEHHLSEETKCSASLFSSQCSELEDLTANTNTQDPFLIGSSKQMRHQSESQGVGLSDKELVSDDEERGTGLEENNQEEQSMDSNLGEAASGCESETSVSEDCSGLSSQSDILTTQQRDTMQHNLIKLQQEMAELEAVLEQHGSQPSNSYPSIISDSSALEDLRNPEQSTSEKAVLTSQKSSEYPISQNPEGLSADKFEVSADSSTSKNKEPGVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVVDVEEQQLEESGPHDLTETSYLPRQDLEGTPYLESGISLFSDDPESDPSEDRAPESARVGNIPSSTSALKVPQLKVAESAQSPAAAHTTDTAGYNAMEESVSREKPELTASTERVNKRMSMVVSXXXXXXXXXXXXXXXXXXXXXTXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXLNEHDFEVRGDVVNGRNHQGPKRARESQDRKXXRXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXVVQPDXXXXXXGFHXXXQMXXXXXXXXXXXXXXXXXXXXXXXXXXXXPQIPHSHY
>CBX4_HUMAN__O00257 RecName: Full=E3 SUMO-protein ligase CBX4; EC=6.3.2.-; AltName: Full=Chromobox protein homolog 4; AltName: Full=Polycomb 2 homolog; Short=Pc2; Short=hPc2;
XELPAVGEHXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXTWEPEENXXDPRLLIAFQNRERQEQLMGYRKRGPKPKPLVVQVPTFARRSNVLTGLQDSSTDNRAKLDLGAQGKGQGHQYELNSKKHHQYQPHSKERAGKPPPPGKSGKYYYQLNSKKHHPYQPDPKMYDLQYQGGHKEAPSPTCPDLGAKSHPPDKWAQGAGAKGYLGAVKPLAGAAGAPGKGSEKGPPNGMMPAPKEAVTGNGIGGKMKIVKNKNKNGRIVIVMSKYMENGMQAVKIKSGEVAEGEARSPSHKKRAADERHPPADRTFKKAAGAEEKKVEAPPKRREEEVSGVSDPQPQDAGSRKLSPTKEAFGEQPLQLTTKPDLLAWDPARNTHPPSHXPXPXPXXXXXXXXXXXHAVGLNLSHVRKRCLSETHGEREPCKKRLTARSISTPTCLGGSPAAERPADLPPAAALPQPEVILLDSDLDEPIDLRCVKTRSEAGEPPSSLQVKPETPASXXVXVXXXXAPTTTAEKPPAEAQDEPAESLSEFKPXXXXXXXXXXXXXXXXXXXXXYVTV
>CHD3_HUMAN__Q12873 RecName: Full=Chromodomain-helicase-DNA-binding protein 3; Short=CHD-3; EC=3.6.4.12; AltName: Full=ATP-dependent helicase CHD3; AltName: Full=Mi-2 autoantigen 240 kDa protein; AltName: Full=Mi2-alpha; AltName: Full=Zinc finger helicase; Short=hZFH;
XKAADTVILWXXXXNDXXXXSFPPGLCWGDRMPDKDDIRLLPSALGVKKRKRGPKKQKENKPGKPRKRKKRDSEEEFGSERDEYREKSESGGSEYGTGPGRKXXXKHREKXEXXTXRRXKGEGDGGQKQVEQKSSATLLLTWXLEDXXXXFSXXDXXXXXXYXXXXXXXRXXIAKKNPKIPMSKMMTIXXAKWREFSXNNXXXXXXXXXXXXXXXXXXXXXXXVXXAVSSATPIAPSGPXALXXXPAADIQPPPIRRAKTKEGKGPGHKRRSKSPRVPDGRKKLRGKKMAPLKIKLGLLGGKRKKGGSYVFQSDEGPEPEAEESDLDSGSVHSASGRPDGPVRTKKLKRGRPGRKKKKVLGCPAVAGEEEVDGYEXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXGKWSCPHCEKEGVQWEAKXXXXXYXXXGXXXGXKXXEDDHMEYXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXKILHWRWGEPPVAVPAPQQADGNPDVXXXRPLQGRSEREXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXRKNDMDEPPPLDYGSGEDDGKSDKRKVKDPHYAEMEEKYXXXXXXXXXXXXXXXIXXXXXXXXXXXXXXXXXXXXXXQSTWEEDEMNIPEYEEHKQSYWRHRELIMGEDPAQPRKYXXXXKELQGDGPPSSPTNDPTVKYETQPRFITATGGTLXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXRXIIRENEFSFEDNAIKGGKKAFKXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXFLXXXXXXSXXXQIKKLHDLLXXXXXXXXXADVXXXXXXXXXXXVRXXXXXXXXXXXXXXXXXXXXXXXXXGXXXXXXLXXXXXXXXXXXXXXXXXXXXAMXXXKLPXGAYEGGAXXXXXXXXXXXQKMLXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXGXXGXLXXEAIDRXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXDIQAFSRAHXXXXXXXXXXXXXXXXXXXXXRITQVAKXKMMXTHLVVRPGLGSKAGSMSKQELDDILKFGTEELFKDENEGENKEEDSSVIHYDNEAIARLLDRNQDATEDTDVQNMNEYLSXXKVAXXXXREEDXIEEIEREIIKQEENVDPDYWEKLLRHHYEQQQEDLARNLGKGKRVRKQVNYNDAAQEDQDNQSEYSVGSEEEDEDFDERPEGRRQSKRQLRNEKDKPLPPLLARVGGNIEVLGXXTXXXXXXLNAVMRWGMXXXXAXTTQWLVRXXXGXXXXXXXXXXXXXXXXLCXPGADGSETFADGVPREGLSRQQVLTRIGVMSXXXKKVQEFEHINGRWSMPELMPDPSADSKRSSRASSPTKTSPTTPEASATNSPCTSKPATPAPSEKGEGIRTPLEKEXAXNQXEKPEKNSRIGEKMETEADAPSPAPSLGERLEPRKIPLEDEVPGVPGEMEPEPGYRGDREKSATESTPGERGEEKPLDGQEHRERPEGETGDLGKREDVKGDRELRPGPRDEPRSNGRREEKTEKPRFMFNIADGGFTELHTLWQNEERAAXXXGXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXEPXXXXXNKGNXXEXXXXXXXXXXXXXXXXXXXXXXXXXXXXLNLSXEPAHPAMALHARFAEAECLAESHQHLSKESLAGNKPANAVLHKVLNQLEXLLXDMKADVTRLPATLSRIPPIAARLQMSERSILSRLASKGTEPHPTPAYPPGPYATPPGYGAAXXXXXXXXXXXXXXXXXXXXXGSFITAATNGPPVLVKKEKEMVGALVSDGLDRKEPRAGEVICIDD
>COM1_HUMAN__Q99708 RecName: Full=DNA endonuclease RBBP8; EC=3.1.-.-; AltName: Full=CtBP-interacting protein; Short=CtIP; AltName: Full=Retinoblastoma-binding protein 8; Short=RBBP-8; AltName: Full=Retinoblastoma-interacting protein and myosin-like; Short=RIM; AltName: Full=Sporulation in the absence of SPO11 protein 2 homolog; Short=SAE2;
XNISGSSCGSPNSADTSSDFKDLWTKLKECHDXEVQGLQVKVTXXKXXRXXXXXRLXXFXTKNQQLREQQKVLHXXIKXXXXXXXXXXXXRCAVTEEHMRKKQQEFENIRQQNLKLITELMNERNTLQEENKKLSEQLQQKIENDQQHQAAELECEEDVIPDSPITAFSFSGVNRLRRKENPHVRYIEQTHTKLEHSVCANEMRKVSKSSTHPQHNPNENEILVADTYDQSQSPMAKAHGTSSYTPDKSSFNLATVVAETLGLGVQEESETQGPMSPLGDELYHCLEGNHKKQPFEESTRNTEDSLRFSDSTSKTPPQEELPTRVSSPVFGATSSIKSGLDLNTSLSPSLLQPGKKKHLKTLPFSNTCISRLEKTRSKSEDSALFTHHSXGSEVNKIIIQSSNKQILINKNISESLGEQNRTEYGKDSNTDKHLEPLKSLGGRTSKRKKTEXXSXHEVSCPQASFDKENAFPFPMDNQFSMNGDCVMDKPLDLSDRFSAIQRQEKSQGSETSKNKFRQVTLYEALKTIPKGFSSSRKASDGNCTLPKDSPGEPCSQECIILQPLNKCSPDNKPSLQIKEENAVFKIPLRPRESLETENVLDDIKSAGSHEPIKIQTRSDHGGCELASVLQLNXCRTGKIKSLQNNQDVSFENIQWSIDPGADLSQYKMDVTVIDTKDGSQSKLGGETVDMDCTLVSETVLLKMKKQEQKGEKSSNEERKMNDSLEDMFDRTTHEEYESCLADSFSQAADEEEELSTATKKLHTHGDKQDKVKQKAFVEPYFKGDERETSLQNFPHIEVVRKKEERRXXXXXXXXXXXXXYAXXPAXEREKKLASCSRHRFRYIPXNTPENFWEVGFPSTQTCMERGYIKEDLDPCPRPKRRQPYNAIFSPKGKEQKT
>CTBP1_HUMAN__Q13363 RecName: Full=C-terminal-binding protein 1; Short=CtBP1; EC=1.1.1.-;
XGSSHLLNKGLPLGVRPPIMNGPLHPRPXVALLDGXXXXXXXXXXXXXXXXXXXXXXXXXXXXEKXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXREXXXVQSVEQIREVASGAXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXNDFXXXXXXXGAXXXNTAXXXXXXEKALAQALKEGRIRGAALDVHESEPFSFSQGPLKDAPNLICTPHAAWYSEQASIEMREEAAREIRRAITGRIPDSLKNCVNKDHLTAATHWASMDPAVVHXELNGAXXXYPPXVXXXXPXGIPAAVEGIVPSAMSLSHGLPPVAHPPHAPSPGQTVKPEADRDHASDQL
>CTNA1_HUMAN__P35221 RecName: Full=Catenin alpha-1; AltName: Full=Alpha E-catenin; AltName: Full=Cadherin-associated protein; AltName: Full=Renal carcinoma antigen NY-REN-13;
XTAVHAGNINXXXXXXXXXXXXXXXXXXLXXXXTQVTTLVNTNSKGPSNKKRGRSKKAHVLAASVEQATENFLEKGDKIAKESQFLKXXLVAAVEDVRKQGDLMKAAAGEFADDPCSSVKRGXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXLGIQYKALXXXVDKLNIMAAKRQQELKDVGHRDQMAAARGIXXXXXXXXXXXXXXXXXXXDVXXXXXNRXXXXXXLQQAXXXISNAAQATASDDASQHQGXXXGELAYALNNFDXXXIVDPLSFSEERFRPSLEERLESIISGAALMADSSCTRDDRRERIVAECNXVRXXLQDLLSEYMGNAGRKERSDALNSAIDKMTKKTRDLRRQLRKAVMDHVSXXXXXXXXXXXXXXEXXXXXNEXEVKEYAQVFXXXXXXXXXXXXXXXXXXXXXXXXXLXRXXXXXXXXXXXXXXXXXXXXXXXXQSXXAQENMDLFKXQWEXXVXXLXXXXXXXXXXDXXXXXXXXXXXXXXXXXXXXXXXXXXXXLDRTAGXXXXXAAXVIXVVTSXMDNYEPGVYTEKVLEATKLLSNTVMPRFTEQVEAAVEALSSDPAQPMDENEFIDASRLXXXXXXXXXXAVLMIRTPEELDDSDFETEDFDVRSRTSVQTEDDQLIAGQSARAIMAQLPQEQKAKIAEQVASFQEEKSKLDAEVSKWDDSGNDIIVXAKQMXXXXMEMTDFTRGKGPLKNTSDVISAAKKIAEAGSRMDKLGRTIADHXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXTKXQKSQGMASLNLPAVSWKMKAPEKKPLVKREKQDETQTKIKRASQKKHVNPVQALSEFKAMDSI
>HDAC2_HUMAN__Q92769 RecName: Full=Histone deacetylase 2; Short=HD2; EC=3.5.1.98;
XXYSQGGXXXXXXXXXXXXXXXXXXGQGXXMKXHRIRMXXXXXXXXXXXXXXXXYRPHKATAEEMTKYHSDEYIKFLRSIRPDNMSEYSKQMQRFNVXXDXXXXXXXXXXXXXXXXXXXXGAVKLNRQXTDMAVNWAGGLHXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXYXXXXXXXXXXXXXXXXXXXXGDLRXXXAXXXXXYXXNFPMRDXXDDEXYGQXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXNXYXXXXXXXFKXHISPSNMTNQNTPEYMEKIKQRLFENLRMLPHAPGVQMQAIPEDAVHEDSGDEDGEDPDKRISIRASDKRIACDEEFSDSEDEGEGGRRNVADHKKGAKKARIEEDKKETEDKKTDVKEEDKSKDNSGEKTDTKGTKSEQLSNP
>HIC1_HUMAN__Q14526 RecName: Full=Hypermethylated in cancer 1 protein; Short=Hic-1; AltName: Full=Zinc finger and BTB domain-containing protein 29;
XTFPEADILLKSGECAGQTMLDTMEAPGHSRQLLLQLXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXYCHLRGXXXXXXGYAPYGRPGRGLRAATPVIQACYPSXVGXXXXXAAEXPSGPEAAVNTHCAELYAXXXGPAAXLCXXXXXXXXXCGLDLSKKSPPGSAAPERPLAERELPXRXDSXPSAGPAAYKEPPLALPSLPPLPFQKLEEAAPPSDPFRGGSGSPGPEPPGRPDGPSLLYRWMKHEPGLGSYGDELGRERGSPSERCEERGGDAAVSPGGPPLGLAPPPRYPGSLDGPXAXXDGDDYKSSSEETGSSEDPSPPGGHLEGYPCPHLAYGEPXXFXXXXXXXXXXXXXXXXXEQLNAHVEAHVXXXEALYGRAEXXEVXXGXAGLGPPFXXXGDKVAGAPGGLGEXLRPYRCASCDKSYKDPATLRQHEKTHWXTRPXPCTICGKKFTQRGTMTRHMRSHLXXXXXXXXXXXXXXXXXXRLTEHMRIHSXXKPXXCQVCGXXXXXXRNLISHMKMHAVXXAXXXXXXXAGLGGLPGVPGPDGKGKLDFPEGVFAVXRXTAEXLSLKQXDKAXXXXLLAQXXXXXXXXXXXXXXXXXXXXXXXXXXLXPDKAAEVLSQGAHLAAGPDGRTIDRFSPT
>IKZF1_HUMAN__Q13422 RecName: Full=DNA-binding protein Ikaros; AltName: Full=Ikaros family zinc finger protein 1; AltName: Full=Lymphoid transcription factor LyF-1;
XDADEGQDMSQVSGKESPPVSDTPDEGDEPMPIPEDLSTTSGGQQSSKSDRVVASNVKVETQSDEENGRACEMNGEECAEDLRMLDASGEKMNGSHRDQGSSALSGVGGIRXXXXXXXXXXXXXXXXXXXXXXXXXRSHTXERPFQCNQCGXXXXXXGNXLRHIKLHXXXXXXXXXXXXXXXXXXXXXXXHLRTHSXXKPXXCGYCGRSYKQRSSLEEHKERCHNYLESMGLPGTLYPVIKEETNHSEMAEDLCKIGSERSLVLDRLASNVAKRKSSMPQKFLGDKGLSDTPYDSSASYEKENEMMKSHVMDQAINNAINYLGAESLRPLVQTPPGGSEVVPVISPMYQLHKPLAEGTPRSNHSAQDSAVENLLLLSKAKLVPSEREASPSNSCQDSTDTESNNEEQRSGLIYLTNHIAPHARNGLSLKEEHRAYDLLRAASENSQDALRVVSTXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXFSSHITRGEHRFHMS
>ITF2_HUMAN__P15884 RecName: Full=Transcription factor 4; Short=TCF-4; AltName: Full=Class B basic helix-loop-helix protein 19; Short=bHLHb19; AltName: Full=Immunoglobulin transcription factor 2; Short=ITF-2; AltName: Full=SL3-3 enhancer factor 2; Short=SEF-2;
XHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLASGHFTGSNVEDRSSSGSWGNGGHPSPSRNYGDGTPYDHMTSRDLGSHDNLSPPFVNSRIQSKTERGSYSSYGRESNLQGCHQQSLLGGDMDMGNPGTLSPTKPGSQYYQYSSNNPRRRPLHSSAMEVQTKKVRKVPPGLPSSVYAPSASTADYNRDSPGYPSSKPATSTFPSSFFMQDGHHSXDPWXXXSGMNQPGYAGMLGNSSHIPQSSSYCSLHPHERLSYPSHSSADINSSLPPMSTFHRSGTNHYSTSSCTPPANGTDSIMANRGSGAAGSSQTGDALGKALASIYSPDHTNNSFSSNPSTPVGSPPSLSAGTAVWSRNGGQASSSPNYEGPLHSLQSRIEDRLERLDDAIHVLRNHAVGPSTAMPGGHGDMHGIIGPSHNGAMGXLXSXYGTGLLSANRHSLMVGTHREDGVALRGSHSLLPNQVPVPQLPVQSATSPDLNPPQDPYRGMPPGLQGQSVXXGXSEIKSDDEGDENLQDTKSSEDKKLDDDKKDIKSITSNNDDEDLTPEQKAEREKERRMANNARERLRVRDINEAXXXXGRMVQLHLKXXXXXXXXXXXXXXXXXXXXXXXXXRXRNLNPKAACLKRREEEKVSSEPPPLSLAGPHPGMGDASNHMGQM
>KAT2B_HUMAN__Q92831 RecName: Full=Histone acetyltransferase KAT2B; EC=2.3.1.48; AltName: Full=Histone acetyltransferase PCAF; Short=Histone acetylase PCAF; AltName: Full=Lysine acetyltransferase 2B; AltName: Full=P300/CBP-associated factor; Short=P/CAF;
XSEAGXAXPXXCXAXAGAGAGPGALPPQPAALPPAPPQGSPCAAAAGGSGXXGPATXVXXXGTAEGPXXXGSARIAVKKAQLRSAPRAKKLEKLGVXXXXXXXXXXKCNGWKNPNXSXTXPRADLQQIIVSLTEXXXXXXXXXXXXVSHLEXXSXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXKPVVEGSLEKKPPFEKPSIEQGVNNFVQYKFSHXXXXEXXXXXXXXXXXXXXXXXXXXXAPSQRRLRSPNDDISGXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXQLLXQARQEKDKLPLEKRXXXXXXXXXXXXXXEEXVXSQNSPIWDQDFLSASSRTSQLGIQTVINPPPVAGTISYNXTXXSLEQPNAGSSSPACKASSGLEANPGEKRKMTDSHVLEEAKKPRVMGDIPMELINEVMSTITDPAAMLGPETNFLSAHSARDEAARLEERRGVXXFHVVGNSXXXXXXXXXXXXXXXXXXXXXXXXPXXXXXYXTXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXIXXXXXXXXXXYPGLXCFKDGVRQIPIESIPGIRETGWKPSGKEKSKEPRDPDQLYSTLKSILQQVKSHQSAWPFMEPVKRXXXXXYXXVXXXXXXXXXXXXXLXXXXXXXXXXXXXXXXXXXXXCKXXXXXXXXXXXXXXXXXXXXXXXXXXAGLIDK
>LCORL_HUMAN__Q8N3X6 RecName: Full=Ligand-dependent nuclear receptor corepressor-like protein; Short=LCoR-like protein;
XDKGRERMAXXXXXXXXXAXXXXCRSPRCAAERXGFRXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXFEXXEPEELTDWSXDEKXXFCXXXRXXXSDCIPSLDSSQSTPTEELSSQGQSNTDKIECQAENYLNALFRKKDLPQNCDPNIPLVAQXLXXXXXXQFAIEYISKSGKTQENRNGSIGPSIVCKSIQMNQAENSLQEEQEGPLDLTVNRMQEQNTQQGDGVLDLSTKKTSIKSEESSICDPSSENSVAGRLHRNREDYVERSAEFADXXLSXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXLEAXXXXKPASFKNKTRDFHDSYSYKDSXEXXXXXXXXXXXXRAQAEXXEKSKLNLLETSEXXXPXASTYXXQXTLQKMVTQFKEKNESLQYETSNPTVQLKIPQLRVSSVSKSQPDGSGLLDVMYQVSKXSSVLEGSALQKLKNILPKQNKIECSGPVTHSSVDSYFXHGDLSPLCLNSKNGTVDGTSENTEDGLDRKDSKQPRKKRGRYRQYDHEIMEEAIAMVMSGKMSVSKAQGIYGVPHSTLEYKVKERSGTLKTPPKKKLRLPDTGLYNMTDSGTGSCKNSSKPV
>LCOR_HUMAN__Q96JN0 RecName: Full=Ligand-dependent corepressor; Short=LCoR; AltName: Full=Mblk1-related protein 2;
XQRMIQQFAAEYTSKNSSTQDPSQPNSTKNQSLPKASPVTTSPTAATTQNPVLSKLLMADQDSPLDLTVRKSQSEPSEQDGVLDLSTKKSPCAGSTSLSHSPGCSSTQGNGRPGRPSQYRPDGLRSGDGVPPRSLQDGTREGFGHSTSLKVPLARSLQISEELLSRNQLSTAASLGPSGLQNHGQHLILSREASXXXXHYEXXLXRMKXXGXGXXXXISDLPFLAENSAFPKMALQAKQDGKKDVSHSSPVDLKIPQVRGMDLSWESRTGDQYSYSSLVMGSQTESALSKKLRAILPKQSRKSMLDAGPDSWGSDAEQSTSGQPYPTSDQEGDPGSKQPRKKRGRYRQYNSEILEEAISVVMSGKXXXSKAQSIYGIPHSTLEYKVKERLGTLKNPPKKKMKLMRSEGPDVSVKIELDPQGEAAQSANESKNE
>MDS1_HUMAN__Q13465 RecName: Full=MDS1 and EVI1 complex locus protein MDS1; AltName: Full=Myelodysplasia syndrome 1 protein; AltName: Full=Myelodysplasia syndrome-associated protein 1;
XRSKGRARKLATNNECVYGNYPEIPLEEMPDADGVASTPSLNIQEPCSPATSSEAFTPKEGSPYKAPIYIPDDIPIPAEFELRESNMPGAGLGIWTKRKIXXGEKFGPYVGEQRSNLKDPSYGWEVHLPXXXXXXXXXWXXXXXXXXXXXXXXXXXXXXXXXXQCAFLS
>NOL4L_HUMAN__Q96MY1 RecName: Full=Nucleolar protein 4-like;
XSDSTWMSADPHLASSLSPSQDERMRSPQNLHSQEDDDSXXEXGSGNGSSTLNPSTSSSTQGDPAFPEMNGNGAVAPMDFTTAAEDQPINLCDKLPPATALGTASYPSDGCGADGLRSRVKYGVKTTPESPPYSSGSYDSIKTEVSGCPEDLTVGRAPTADXXXXXHXXHEDNDKMNDSEGMDPERLKAFNMFVXXXXXXXXDRMVPISKQPKEKIQAIIESCSRQFPEFQERARKRIRTYLKSCRRMKKNGMEMTRPTPPHLTSAMAENILAAACESETRKAAKRMRLEIYQSSQDEPIALDKQHSRDSAAITHSTYSLPASSYSQDPVYANGGLNYSYRGYGALSSNLQPPASLQTGNHSNGPTDLSMKGGASTXSXXPXPTPSSTSTSRPVPTAQLSPTEISAVRQLIXXXXXXXXXXXXXXXXXXXLILQQN
>NRIP1_HUMAN__P48552 RecName: Full=Nuclear receptor-interacting protein 1; AltName: Full=Nuclear factor RIP140; AltName: Full=Receptor-interacting protein 140;
XTHGEELGSDVHQDSIXLTYXEGLLMHQAAGGSGTAVDKKSAGHNEEDQNFNISGSAFPTCQSNGPVLNTHTYQGSGMLHLKKARLLQSSEDWNAAKRKRLSDSIMNLNXXKEXXLAGMVDSVPKGKQDSTLLASLLXXXXXXXXXVXXSQQIXXXXKEQGYALSHDSLKXXKDLRCYXVASSHLKTLLKKSKVKDQKPDTNLPDVTKNLIRDRFAESPHHVGQSGTKVMSEPLSCAARLQAVASMVEKRASPATSPKPSVACSQLALLXXSEAHLQQYSREHALKTQNANQAASERLAAMARLQENGQKDVGSYQLPKGMSSHLNGQARTSSSKLMASKSSATVFQNPMGIIPSSPKNAGYKNSLERNNIKQAANNSLXXHXLKSQTIPKPMNGHSHSERGSIFEESSTPTTIDEYSDNNPSFTDDSSGDESSYSNCVPIDLSCKHRTEKSESDQPVSLDNFTQSLLNTWDPKVPDVDIKEDQDTSKNSKLNSHQKVTLXQXXLGHKNEENVEKNTSPQGVHNDVSKFNTQNYARTSVIESPSTNRTTPVSTPPLLTSSKAGSPINLSQHSLVIKWNSPPYVCSTQSEKLTNTASNHSMDLTKSKDPPGEKPAQNEGAQNSATFSASKLLQNLAQCGMQSSMSVEEQRPSKQLLTGNTDKPIGMIDRLNSPLLSNKTNAVEENKAFSSQPTGPEPGLSGSEIENLLERRTVLQLLLGNPNKGKSEKKEKTPLRDESTQEHSERALSEQILMVKIKSEPCDDLQIPNTNVHLSHDAKSAPFLGMAPAVQRSAPALPVSEDFKSEPVSPQDFSFSKNGLLSRLLRQNQDSYLADDSDRSHRNNEMALLESKNLCMVPKKRKLYTEPLENPFKKMKNNIVDAANNHSAPEVLYGSLLNQEELKFSRNDLEFKYPAGHGSASESEHRSWARESKSFNVLKQLLLSENCVRDLSPHRSNSVADSKKKGHKNNVTNSKPEFSISSLNGLMYSSTQPSSCMDNRTFSYPGVVKTPVSPTFPEHLGCAGSRPESGLLNGCSMPSEKGPIKWVITDAEKNEYEKDSPRLTKTNPILYYMLQKGGNSVTSRETQDKDIWREASSAESVSQVTAKEELLPTAETKASFFNLRSPYNSHMGNNASRPHSANGEVYGLLGSVLTIKKESE
>RBBP5_HUMAN__Q15291 RecName: Full=Retinoblastoma-binding protein 5; Short=RBBP-5; AltName: Full=Retinoblastoma-binding protein RBQ-3;
XNLELLESFGQNYPXEAXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXSTXXXXXQWDVLXXXCDXXXXXPSPILKVQYHPRDXNKVLVCPXXXXXXXXXLXDSKHVVLPVDDXXXXNVVXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXSFRVXXXXXXXXAIKSXXXXXXXXXXXXXXXXXXXXXXXXXXILTCGRDGEPEPMQKLQDLVNRTPWKKXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXWXAFAPDFKELDENVEYXXRXSEFDIEDEDKSEPEQTGADAAEDEEVDVTSVDPIAAFCSSDEELEDSKALLYLPIAPEVEDPEENPYGPPPDAVQTSLMDEGASSEKKRQSSADGSQPPKKKPKTTNIELQGVPNDEVHPLLGVKGDGKSKKKQAGRPKGSKGKEKDSPFKPKLYKGDRGLPLEGSAKGKVQAELSQPLTAGGAISELL
>SOBP_HUMAN__A7XYQ1 RecName: Full=Sine oculis-binding protein homolog; AltName: Full=Jackson circler protein 1;
XXEMEKEGRPPENKRSRKPAHPVKREINEEMKNFAENTMNELLXWYGYDKVXXKXGEDIEFRSYPTDGESRQHISVLKENSLPKPKLPEDSVISPYNISTGYSGLATGNGLSDSPAGSKDHGSVPIIVPLIPXXFIKXPAEDDXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXRNKARDEDGHAENFPQQHYAKETPRXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXAGLCSTLHPPMENKAEGTGVQLLTPDSWNIPLTDARRKAPSPVATAGQSQGPGPSASTTVSPSDTANCSVTKIPTPVPKSIPISETPNIPPVSVQPPASIGPPLGVPPRSPPMVMTNRGPVPLPIFMEQQIMQQIRPPFIRGPPHHASNPNSPLSNPMLPGIGPPPGGPRNLGPTSSPMHRPMLSPHIHPPSTPTMPGNPXGLLXXXXXGAXLPSLPFPPVSMMPNGPMPVPQMMXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXPIPHVSDSKPPNGFSSNGENFIPNAPGDSAAAGGKPSGHSLSPRDSKQGSSKSADSPPGCSGQALSLAPTPAEHGRSEVVDLTRRAGSPPGPPGAGGQLGFPGVLQGPQDGVIDLTVGHRARLHNVIHRALHAHVKAEREPSAAERRTCGGCRDGHCSPPAAGDPGPGAPAGPEXXXACNVIVNGTRGAAAEGAKSAEPXXEQXXXXXXXAXPKKLLSPEEPAVSELESVKENNCASNCHLDGEAAKKLMGEEALAGGDKSDPNLNNPADEDHAYALRMLPKTGCVIQPVPKPAXKAAMAPCIISSPMLSAGPEDLEPPLKRRCLRIRNQNK
>ZN219_HUMAN__Q9P2Y4 RecName: Full=Zinc finger protein 219;
XEGSRPRAPSGHLAPSPPAFDGELDLQRYSNGPAVSAGSLGMGAVSWSESRAXXRRXPXXXXXXXXXXXXXXXXXXXXXXXXXAFQCPHCGHRAAQRALLRSHLRTHQPERPRSPAARLLLELEERALLREARLGRARSSGGMQATPATEGLARPQAPSSSAFRCPYCKGKFXTXAXRERHXHXXXXXXXXXXXXXXXXQEEELLHHSLTAHGAPERPLAATSAAPXXQXQXQXXXQXEPRSVPQPEPEPEPEREATPTPAPAAPEEXXAXPEFRCQVCGQSFXXXWFLKGHXRXXXXXXXXXXXXXXXXXXXXXXXKXXMKVHASKLGPLRAPGPASGPARAPQPPDLGLLAYEPLGPALLLAPAPTPAERREPPSLLGYLSLRAGEGRPNGEGAEPGPGRSFGGFRPLSSALPARARRHRAEXPXXXXXVVXAXXETWARGRSLGSLASLHPRPGEGPGHSASXXGXQARSTATQEENGLLVGGTRPEGGRGATGKDCPFCGKSFXSXHHLKVHLRVHTGERPYKCPHCDYAGTQSGSLKYHLQRHHREQRSGAGPGXXXEXXXPSQRGSAPQSGAKPSPQPATWVEGASSPRPPSSGAGPGSRRKPASPGRTLRNGRGGEAEPLDLSLRAGPGXEAXPXGXXXXXXXXXXXXXXXXXMALHLQVHHSRXAXGXRPPQADASPPYARVPSGETPPSPSQEGEEGSGLSRPGEAGLGGQER
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>ATX1L_HUMAN__P0C7T5 RecName: Full=Ataxin-1-like; AltName: Full=Brother of ataxin-1; Short=Brother of ATXN1;
MKPVHERSQECLPPKKRDLPVTSEDMGRTTSCSTNHTPSSDASEWSRGVVVAGQSQAGARVSLGGDGAEAITGLTVDQYGMLYKVAVPPATFSPTGLPSVVNMSPLPPTFNVASSLIQHPGIHYPPLHYAQLPSTSLQFIGSPYSLPYAVPPNFLPSPLLSPSANLATSHLPHFVPYASLLAEGATPPPQAPSPAHSFNKAPSATSPSGQLPHHSSTQPLDLAPGRMPIYYQMSRLPAGYTLHETPPAGASPVLTPQESQSALEAAAANGGQRPRERNLVRRESEALDSPNSKGEGQGLVPVVECVVDGQLFSGSQTPRVEVAAPAHRGTPDTDLEVQRVVGALASQDYRVVAAQRKEEPSPLNLSHHTPDHQGEGRGSARNPAELAEKSQARGFYPQSHQEPVKHRPLPKAMVVANGNLVPTGTDSGLLPVGSEILVASSLDVQARATFPDKEPTPPPITSSHLPSHFMKGAIIQLATGELKRVEDLQTQDFVRSAEVSGGLKIDSSTVVDIQESQWPGFVMLHFVVGEQQSKVSIEVPPEHPFFVYGQGWSSCSPGRTTQLFSLPCHRLQVGDVCISISLQSLNSNSVSQASCAPPSQLGPPRERPERTVLGSRELCDSEGKSQPAGEGSRVVEPSQPESGAQACWPAPSFQRYSMQGEEARAALLRPSFIPQEVKLSIEGRSNAGK
>BRCA1_HUMAN__P38398 RecName: Full=Breast cancer type 1 susceptibility protein; EC=6.3.2.-; AltName: Full=RING finger protein 53;
MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNRAKRLLQSEPENPSLQETSLSVQLSNLGTVRTLRTKQRIQPQKTSVYIELGSDSSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFSETDVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSSLLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKADLAVQKTPEMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESAFKTKAEPISSSISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCTELQIDSCSSSEEIKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSDTFPELKLTNAPGSFTKCSNTSELKEFVNPSLPREEKEEKLETVKVSNNAEDPKDLMLSGERVLQTERSVESSSISLVPGTDYGTQESISLLEVSTLGKAKTEPNKCVSQCAAFENPKGLIHGCSKDNRNDTEGFKYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSFAPFSNPGNAEEECATFSAHSGSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITAGFPVVGQKDKPVDNAKCSIKGGSRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFPIKSFVKTKCKKNLLEENFEEHSMSPEREMGNENIPSTVSTISRNNIRENVFKEASSSNINEVGSSTNEVGSSINEIGSSDENIQAELGRNRGPKLNAMLRLGVLQPEVYKQSLPGSNCKHPEIKKQEYEEVVQTVNTDFSPYLISDNLEQPMGSSHASQVCSETPDDLLDDGEIKEDTSFAENDIKESSAVFSKSVQKGELSRSPSPFTHTHLAQGYRRGAKKLESSEENLSSEDEELPCFQHLLFGKVNNIPSQSTRHSTVATECLSKNTEENLLSLKNSLNDCSNQVILAKASQEHHLSEETKCSASLFSSQCSELEDLTANTNTQDPFLIGSSKQMRHQSESQGVGLSDKELVSDDEERGTGLEENNQEEQSMDSNLGEAASGCESETSVSEDCSGLSSQSDILTTQQRDTMQHNLIKLQQEMAELEAVLEQHGSQPSNSYPSIISDSSALEDLRNPEQSTSEKAVLTSQKSSEYPISQNPEGLSADKFEVSADSSTSKNKEPGVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVVDVEEQQLEESGPHDLTETSYLPRQDLEGTPYLESGISLFSDDPESDPSEDRAPESARVGNIPSSTSALKVPQLKVAESAQSPAAAHTTDTAGYNAMEESVSREKPELTASTERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKMLNEHDFEVRGDVVNGRNHQGPKRARESQDRKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQIPHSHY
>CBX4_HUMAN__O00257 RecName: Full=E3 SUMO-protein ligase CBX4; EC=6.3.2.-; AltName: Full=Chromobox protein homolog 4; AltName: Full=Polycomb 2 homolog; Short=Pc2; Short=hPc2;
MELPAVGEHVFAVESIEKKRIRKGRVEYLVKWRGWSPKYNTWEPEENILDPRLLIAFQNRERQEQLMGYRKRGPKPKPLVVQVPTFARRSNVLTGLQDSSTDNRAKLDLGAQGKGQGHQYELNSKKHHQYQPHSKERAGKPPPPGKSGKYYYQLNSKKHHPYQPDPKMYDLQYQGGHKEAPSPTCPDLGAKSHPPDKWAQGAGAKGYLGAVKPLAGAAGAPGKGSEKGPPNGMMPAPKEAVTGNGIGGKMKIVKNKNKNGRIVIVMSKYMENGMQAVKIKSGEVAEGEARSPSHKKRAADERHPPADRTFKKAAGAEEKKVEAPPKRREEEVSGVSDPQPQDAGSRKLSPTKEAFGEQPLQLTTKPDLLAWDPARNTHPPSHHPHPHPHHHHHHHHHHHHAVGLNLSHVRKRCLSETHGEREPCKKRLTARSISTPTCLGGSPAAERPADLPPAAALPQPEVILLDSDLDEPIDLRCVKTRSEAGEPPSSLQVKPETPASAAVAVAAAAAPTTTAEKPPAEAQDEPAESLSEFKPFFGNIIITDVTANCLTVTFKEYVTV
>CHD3_HUMAN__Q12873 RecName: Full=Chromodomain-helicase-DNA-binding protein 3; Short=CHD-3; EC=3.6.4.12; AltName: Full=ATP-dependent helicase CHD3; AltName: Full=Mi-2 autoantigen 240 kDa protein; AltName: Full=Mi2-alpha; AltName: Full=Zinc finger helicase; Short=hZFH;
MKAADTVILWARSKNDQLRISFPPGLCWGDRMPDKDDIRLLPSALGVKKRKRGPKKQKENKPGKPRKRKKRDSEEEFGSERDEYREKSESGGSEYGTGPGRKRRRKHREKKEKKTKRRKKGEGDGGQKQVEQKSSATLLLTWGLEDVEHVFSEEDYHTLTNYKAFSQFMRPLIAKKNPKIPMSKMMTILGAKWREFSANNPFKGSAAAVAAAAAAAAAAVAEQVSAAVSSATPIAPSGPPALPPPPAADIQPPPIRRAKTKEGKGPGHKRRSKSPRVPDGRKKLRGKKMAPLKIKLGLLGGKRKKGGSYVFQSDEGPEPEAEESDLDSGSVHSASGRPDGPVRTKKLKRGRPGRKKKKVLGCPAVAGEEEVDGYETDHQDYCEVCQQGGEIILCDTCPRAYHLVCLDPELDRAPEGKWSCPHCEKEGVQWEAKEEEEEYEEEGEEEGEKEEEDDHMEYCRVCKDGGELLCCDACISSYHIHCLNPPLPDIPNGEWLCPRCTCPVLKGRVQKILHWRWGEPPVAVPAPQQADGNPDVPPPRPLQGRSEREFFVKWVGLSYWHCSWAKELQLEIFHLVMYRNYQRKNDMDEPPPLDYGSGEDDGKSDKRKVKDPHYAEMEEKYYRFGIKPEWMTVHRIINHSVDKKGNYHYLVKWRDLPYDQSTWEEDEMNIPEYEEHKQSYWRHRELIMGEDPAQPRKYKKKKKELQGDGPPSSPTNDPTVKYETQPRFITATGGTLHMYQLEGLNWLRFSWAQGTDTILADEMGLGKTIQTIVFLYSLYKEGHTKGPFLVSAPLSTIINWEREFQMWAPKFYVVTYTGDKDSRAIIRENEFSFEDNAIKGGKKAFKMKREAQVKFHVLLTSYELITIDQAALGSIRWACLVVDEAHRLKNNQSKFFRVLNGYKIDHKLLLTGTPLQNNLEELFHLLNFLTPERFNNLEGFLEEFADISKEDQIKKLHDLLGPHMLRRLKADVFKNMPAKTELIVRVELSPMQKKYYKYILTRNFEALNSRGGGNQVSLLNIMMDLKKCCNHPYLFPVAAMESPKLPSGAYEGGALIKSSGKLMLLQKMLRKLKEQGHRVLIFSQMTKMLDLLEDFLDYEGYKYERIDGGITGALRQEAIDRFNAPGAQQFCFLLSTRAGGLGINLATADTVIIFDSDWNPHNDIQAFSRAHRIGQANKVMIYRFVTRASVEERITQVAKRKMMLTHLVVRPGLGSKAGSMSKQELDDILKFGTEELFKDENEGENKEEDSSVIHYDNEAIARLLDRNQDATEDTDVQNMNEYLSSFKVAQYVVREEDKIEEIEREIIKQEENVDPDYWEKLLRHHYEQQQEDLARNLGKGKRVRKQVNYNDAAQEDQDNQSEYSVGSEEEDEDFDERPEGRRQSKRQLRNEKDKPLPPLLARVGGNIEVLGFNTRQRKAFLNAVMRWGMPPQDAFTTQWLVRDLRGKTEKEFKAYVSLFMRHLCEPGADGSETFADGVPREGLSRQQVLTRIGVMSLVKKKVQEFEHINGRWSMPELMPDPSADSKRSSRASSPTKTSPTTPEASATNSPCTSKPATPAPSEKGEGIRTPLEKEEAENQEEKPEKNSRIGEKMETEADAPSPAPSLGERLEPRKIPLEDEVPGVPGEMEPEPGYRGDREKSATESTPGERGEEKPLDGQEHRERPEGETGDLGKREDVKGDRELRPGPRDEPRSNGRREEKTEKPRFMFNIADGGFTELHTLWQNEERAAISSGKLNEIWHRRHDYWLLAGIVLHGYARWQDIQNDAQFAIINEPFKTEANKGNFLEMKNKFLARRFKLLEQALVIEEQLRRAAYLNLSQEPAHPAMALHARFAEAECLAESHQHLSKESLAGNKPANAVLHKVLNQLEELLSDMKADVTRLPATLSRIPPIAARLQMSERSILSRLASKGTEPHPTPAYPPGPYATPPGYGAAFSAAPVGALAAAGANYSQMPAGSFITAATNGPPVLVKKEKEMVGALVSDGLDRKEPRAGEVICIDD
>COM1_HUMAN__Q99708 RecName: Full=DNA endonuclease RBBP8; EC=3.1.-.-; AltName: Full=CtBP-interacting protein; Short=CtIP; AltName: Full=Retinoblastoma-binding protein 8; Short=RBBP-8; AltName: Full=Retinoblastoma-interacting protein and myosin-like; Short=RIM; AltName: Full=Sporulation in the absence of SPO11 protein 2 homolog; Short=SAE2;
MNISGSSCGSPNSADTSSDFKDLWTKLKECHDREVQGLQVKVTKLKQERILDAQRLEEFFTKNQQLREQQKVLHETIKVLEDRLRAGLCDRCAVTEEHMRKKQQEFENIRQQNLKLITELMNERNTLQEENKKLSEQLQQKIENDQQHQAAELECEEDVIPDSPITAFSFSGVNRLRRKENPHVRYIEQTHTKLEHSVCANEMRKVSKSSTHPQHNPNENEILVADTYDQSQSPMAKAHGTSSYTPDKSSFNLATVVAETLGLGVQEESETQGPMSPLGDELYHCLEGNHKKQPFEESTRNTEDSLRFSDSTSKTPPQEELPTRVSSPVFGATSSIKSGLDLNTSLSPSLLQPGKKKHLKTLPFSNTCISRLEKTRSKSEDSALFTHHSLGSEVNKIIIQSSNKQILINKNISESLGEQNRTEYGKDSNTDKHLEPLKSLGGRTSKRKKTEEESEHEVSCPQASFDKENAFPFPMDNQFSMNGDCVMDKPLDLSDRFSAIQRQEKSQGSETSKNKFRQVTLYEALKTIPKGFSSSRKASDGNCTLPKDSPGEPCSQECIILQPLNKCSPDNKPSLQIKEENAVFKIPLRPRESLETENVLDDIKSAGSHEPIKIQTRSDHGGCELASVLQLNPCRTGKIKSLQNNQDVSFENIQWSIDPGADLSQYKMDVTVIDTKDGSQSKLGGETVDMDCTLVSETVLLKMKKQEQKGEKSSNEERKMNDSLEDMFDRTTHEEYESCLADSFSQAADEEEELSTATKKLHTHGDKQDKVKQKAFVEPYFKGDERETSLQNFPHIEVVRKKEERRKLLGHTCKECEIYYADMPAEEREKKLASCSRHRFRYIPPNTPENFWEVGFPSTQTCMERGYIKEDLDPCPRPKRRQPYNAIFSPKGKEQKT
>CTBP1_HUMAN__Q13363 RecName: Full=C-terminal-binding protein 1; Short=CtBP1; EC=1.1.1.-;
MGSSHLLNKGLPLGVRPPIMNGPLHPRPLVALLDGRDCTVEMPILKDVATVAFCDAQSTQEIHEKVLNEAVGALMYHTITLTREDLEKFKALRIIVRIGSGFDNIDIKSAGDLGIAVCNVPAASVEETADSTLCHILNLYRRATWLHQALREGTRVQSVEQIREVASGAARIRGETLGIIGLGRVGQAVALRAKAFGFNVLFYDPYLSDGVERALGLQRVSTLQDLLFHSDCVTLHCGLNEHNHHLINDFTVKQMRQGAFLVNTARGGLVDEKALAQALKEGRIRGAALDVHESEPFSFSQGPLKDAPNLICTPHAAWYSEQASIEMREEAAREIRRAITGRIPDSLKNCVNKDHLTAATHWASMDPAVVHPELNGAAYRYPPGVVGVAPTGIPAAVEGIVPSAMSLSHGLPPVAHPPHAPSPGQTVKPEADRDHASDQL
>CTNA1_HUMAN__P35221 RecName: Full=Catenin alpha-1; AltName: Full=Alpha E-catenin; AltName: Full=Cadherin-associated protein; AltName: Full=Renal carcinoma antigen NY-REN-13;
MTAVHAGNINFKWDPKSLEIRTLAVERLLEPLVTQVTTLVNTNSKGPSNKKRGRSKKAHVLAASVEQATENFLEKGDKIAKESQFLKEELVAAVEDVRKQGDLMKAAAGEFADDPCSSVKRGNMVRAARALLSAVTRLLILADMADVYKLLVQLKVVEDGILKLRNAGNEQDLGIQYKALKPEVDKLNIMAAKRQQELKDVGHRDQMAAARGILQKNVPILYTASQACLQHPDVAAYKANRDLIYKQLQQAVTGISNAAQATASDDASQHQGGGGGELAYALNNFDKQIIVDPLSFSEERFRPSLEERLESIISGAALMADSSCTRDDRRERIVAECNAVRQALQDLLSEYMGNAGRKERSDALNSAIDKMTKKTRDLRRQLRKAVMDHVSDSFLETNVPLLVLIEAAKNGNEKEVKEYAQVFREHANKLIEVANLACSISNNEEGVKLVRMSASQLEALCPQVINAALALAAKPQSKLAQENMDLFKEQWEKQVRVLTDAVDDITSIDDFLAVSENHILEDVNKCVIALQEKDVDGLDRTAGAIRGRAARVIHVVTSEMDNYEPGVYTEKVLEATKLLSNTVMPRFTEQVEAAVEALSSDPAQPMDENEFIDASRLVYDGIRDIRKAVLMIRTPEELDDSDFETEDFDVRSRTSVQTEDDQLIAGQSARAIMAQLPQEQKAKIAEQVASFQEEKSKLDAEVSKWDDSGNDIIVLAKQMCMIMMEMTDFTRGKGPLKNTSDVISAAKKIAEAGSRMDKLGRTIADHCPDSACKQDLLAYLQRIALYCHQLNICSKVKAEVQNLGGELVVSGVDSAMSLIQAAKNLMNAVVQTVKASYVASTKYQKSQGMASLNLPAVSWKMKAPEKKPLVKREKQDETQTKIKRASQKKHVNPVQALSEFKAMDSI
>HDAC2_HUMAN__Q92769 RecName: Full=Histone deacetylase 2; Short=HD2; EC=3.5.1.98;
MAYSQGGGKKKVCYYYDGDIGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKATAEEMTKYHSDEYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVAGAVKLNRQQTDMAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHGDGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNFPMRDGIDDESYGQIFKPIISKVMEMYQPSAVVLQCGADSLSGDRLGCFNLTVKGHAKCVEVVKTFNLPLLMLGGGGYTIRNVARCWTYETAVALDCEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTPEYMEKIKQRLFENLRMLPHAPGVQMQAIPEDAVHEDSGDEDGEDPDKRISIRASDKRIACDEEFSDSEDEGEGGRRNVADHKKGAKKARIEEDKKETEDKKTDVKEEDKSKDNSGEKTDTKGTKSEQLSNP
>HIC1_HUMAN__Q14526 RecName: Full=Hypermethylated in cancer 1 protein; Short=Hic-1; AltName: Full=Zinc finger and BTB domain-containing protein 29;
MTFPEADILLKSGECAGQTMLDTMEAPGHSRQLLLQLNNQRTKGFLCDVIIVVQNALFRAHKNVLAASSAYLKSLVVHDNLLNLDHDMVSPAVFRLVLDFIYTGRLADGAEAAAAAAVAPGAEPSLGAVLAAASYLQIPDLVALCKKRLKRHGKYCHLRGGGGGGGGYAPYGRPGRGLRAATPVIQACYPSPVGPPPPPAAEPPSGPEAAVNTHCAELYASGPGPAAALCASERRCSPLCGLDLSKKSPPGSAAPERPLAERELPPRPDSPPSAGPAAYKEPPLALPSLPPLPFQKLEEAAPPSDPFRGGSGSPGPEPPGRPDGPSLLYRWMKHEPGLGSYGDELGRERGSPSERCEERGGDAAVSPGGPPLGLAPPPRYPGSLDGPGAGGDGDDYKSSSEETGSSEDPSPPGGHLEGYPCPHLAYGEPESFGDNLYVCIPCGKGFPSSEQLNAHVEAHVEEEEALYGRAEAAEVAAGAAGLGPPFGGGGDKVAGAPGGLGELLRPYRCASCDKSYKDPATLRQHEKTHWLTRPYPCTICGKKFTQRGTMTRHMRSHLGLKPFACDACGMRFTRQYRLTEHMRIHSGEKPYECQVCGGKFAQQRNLISHMKMHAVGGAAGAAGALAGLGGLPGVPGPDGKGKLDFPEGVFAVARLTAEQLSLKQQDKAAAAELLAQTTHFLHDPKVALESLYPLAKFTAELGLSPDKAAEVLSQGAHLAAGPDGRTIDRFSPT
>IKZF1_HUMAN__Q13422 RecName: Full=DNA-binding protein Ikaros; AltName: Full=Ikaros family zinc finger protein 1; AltName: Full=Lymphoid transcription factor LyF-1;
MDADEGQDMSQVSGKESPPVSDTPDEGDEPMPIPEDLSTTSGGQQSSKSDRVVASNVKVETQSDEENGRACEMNGEECAEDLRMLDASGEKMNGSHRDQGSSALSGVGGIRLPNGKLKCDICGIICIGPNVLMVHKRSHTGERPFQCNQCGASFTQKGNLLRHIKLHSGEKPFKCHLCNYACRRRDALTGHLRTHSVGKPHKCGYCGRSYKQRSSLEEHKERCHNYLESMGLPGTLYPVIKEETNHSEMAEDLCKIGSERSLVLDRLASNVAKRKSSMPQKFLGDKGLSDTPYDSSASYEKENEMMKSHVMDQAINNAINYLGAESLRPLVQTPPGGSEVVPVISPMYQLHKPLAEGTPRSNHSAQDSAVENLLLLSKAKLVPSEREASPSNSCQDSTDTESNNEEQRSGLIYLTNHIAPHARNGLSLKEEHRAYDLLRAASENSQDALRVVSTSGEQMKVYKCEHCRVLFLDHVMYTIHMGCHGFRDPFECNMCGYHSQDRYEFSSHITRGEHRFHMS
>ITF2_HUMAN__P15884 RecName: Full=Transcription factor 4; Short=TCF-4; AltName: Full=Class B basic helix-loop-helix protein 19; Short=bHLHb19; AltName: Full=Immunoglobulin transcription factor 2; Short=ITF-2; AltName: Full=SL3-3 enhancer factor 2; Short=SEF-2;
MHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLASGHFTGSNVEDRSSSGSWGNGGHPSPSRNYGDGTPYDHMTSRDLGSHDNLSPPFVNSRIQSKTERGSYSSYGRESNLQGCHQQSLLGGDMDMGNPGTLSPTKPGSQYYQYSSNNPRRRPLHSSAMEVQTKKVRKVPPGLPSSVYAPSASTADYNRDSPGYPSSKPATSTFPSSFFMQDGHHSSDPWSSSSGMNQPGYAGMLGNSSHIPQSSSYCSLHPHERLSYPSHSSADINSSLPPMSTFHRSGTNHYSTSSCTPPANGTDSIMANRGSGAAGSSQTGDALGKALASIYSPDHTNNSFSSNPSTPVGSPPSLSAGTAVWSRNGGQASSSPNYEGPLHSLQSRIEDRLERLDDAIHVLRNHAVGPSTAMPGGHGDMHGIIGPSHNGAMGGLGSGYGTGLLSANRHSLMVGTHREDGVALRGSHSLLPNQVPVPQLPVQSATSPDLNPPQDPYRGMPPGLQGQSVSSGSSEIKSDDEGDENLQDTKSSEDKKLDDDKKDIKSITSNNDDEDLTPEQKAEREKERRMANNARERLRVRDINEAFKELGRMVQLHLKSDKPQTKLLILHQAVAVILSLEQQVRERNLNPKAACLKRREEEKVSSEPPPLSLAGPHPGMGDASNHMGQM
>KAT2B_HUMAN__Q92831 RecName: Full=Histone acetyltransferase KAT2B; EC=2.3.1.48; AltName: Full=Histone acetyltransferase PCAF; Short=Histone acetylase PCAF; AltName: Full=Lysine acetyltransferase 2B; AltName: Full=P300/CBP-associated factor; Short=P/CAF;
MSEAGGAGPGGCGAGAGAGAGPGALPPQPAALPPAPPQGSPCAAAAGGSGACGPATAVAAAGTAEGPGGGGSARIAVKKAQLRSAPRAKKLEKLGVYSACKAEESCKCNGWKNPNPSPTPPRADLQQIIVSLTESCRSCSHALAAHVSHLENVSEEEMNRLLGIVLDVEYLFTCVHKEEDADTKQVYFYLFKLLRKSILQRGKPVVEGSLEKKPPFEKPSIEQGVNNFVQYKFSHLPAKERQTIVELAKMFLNRINYWHLEAPSQRRLRSPNDDISGYKENYTRWLCYCNVPQFCDSLPRYETTQVFGRTLLRSVFTVMRRQLLEQARQEKDKLPLEKRTLILTHFPKFLSMLEEEVYSQNSPIWDQDFLSASSRTSQLGIQTVINPPPVAGTISYNSTSSSLEQPNAGSSSPACKASSGLEANPGEKRKMTDSHVLEEAKKPRVMGDIPMELINEVMSTITDPAAMLGPETNFLSAHSARDEAARLEERRGVIEFHVVGNSLNQKPNKKILMWLVGLQNVFSHQLPRMPKEYITRLVFDPKHKTLALIKDGRVIGGICFRMFPSQGFTEIVFCAVTSNEQVKGYGTHLMNHLKEYHIKHDILNFLTYADEYAIGYFKKQGFSKEIKIPKTKYVGYIKDYEGATLMGCELNPRIPYTEFSVIIKKQKEIIKKLIERKQAQIRKVYPGLSCFKDGVRQIPIESIPGIRETGWKPSGKEKSKEPRDPDQLYSTLKSILQQVKSHQSAWPFMEPVKRTEAPGYYEVIRFPMDLKTMSERLKNRYYVSKKLFMADLQRVFTNCKEYNPPESEYYKCANILEKFFFSKIKEAGLIDK
>LCORL_HUMAN__Q8N3X6 RecName: Full=Ligand-dependent nuclear receptor corepressor-like protein; Short=LCoR-like protein;
MDKGRERMAAAAAAAAAAAAAAQCRSPRCAAERRGFRRELDSWRHRLMHCVGFESILEGLYGPRLRRDLSLFEDCEPEELTDWSMDEKCSFCNLQREAVSDCIPSLDSSQSTPTEELSSQGQSNTDKIECQAENYLNALFRKKDLPQNCDPNIPLVAQELMKKMIRQFAIEYISKSGKTQENRNGSIGPSIVCKSIQMNQAENSLQEEQEGPLDLTVNRMQEQNTQQGDGVLDLSTKKTSIKSEESSICDPSSENSVAGRLHRNREDYVERSAEFADGLLSKALKDIQSGALDINKAGILYGIPQKTLLLHLEALPAGKPASFKNKTRDFHDSYSYKDSKETCAVLQKVALWARAQAERTEKSKLNLLETSEIKFPTASTYLHQLTLQKMVTQFKEKNESLQYETSNPTVQLKIPQLRVSSVSKSQPDGSGLLDVMYQVSKTSSVLEGSALQKLKNILPKQNKIECSGPVTHSSVDSYFLHGDLSPLCLNSKNGTVDGTSENTEDGLDRKDSKQPRKKRGRYRQYDHEIMEEAIAMVMSGKMSVSKAQGIYGVPHSTLEYKVKERSGTLKTPPKKKLRLPDTGLYNMTDSGTGSCKNSSKPV
>LCOR_HUMAN__Q96JN0 RecName: Full=Ligand-dependent corepressor; Short=LCoR; AltName: Full=Mblk1-related protein 2;
MQRMIQQFAAEYTSKNSSTQDPSQPNSTKNQSLPKASPVTTSPTAATTQNPVLSKLLMADQDSPLDLTVRKSQSEPSEQDGVLDLSTKKSPCAGSTSLSHSPGCSSTQGNGRPGRPSQYRPDGLRSGDGVPPRSLQDGTREGFGHSTSLKVPLARSLQISEELLSRNQLSTAASLGPSGLQNHGQHLILSREASWAKPHYEFNLSRMKFRGNGALSNISDLPFLAENSAFPKMALQAKQDGKKDVSHSSPVDLKIPQVRGMDLSWESRTGDQYSYSSLVMGSQTESALSKKLRAILPKQSRKSMLDAGPDSWGSDAEQSTSGQPYPTSDQEGDPGSKQPRKKRGRYRQYNSEILEEAISVVMSGKMSVSKAQSIYGIPHSTLEYKVKERLGTLKNPPKKKMKLMRSEGPDVSVKIELDPQGEAAQSANESKNE
>MDS1_HUMAN__Q13465 RecName: Full=MDS1 and EVI1 complex locus protein MDS1; AltName: Full=Myelodysplasia syndrome 1 protein; AltName: Full=Myelodysplasia syndrome-associated protein 1;
MRSKGRARKLATNNECVYGNYPEIPLEEMPDADGVASTPSLNIQEPCSPATSSEAFTPKEGSPYKAPIYIPDDIPIPAEFELRESNMPGAGLGIWTKRKIEVGEKFGPYVGEQRSNLKDPSYGWEVHLPRSRRVSVHSWLYLGKRSSDVGIAFSQADVYMPGLQCAFLS
>NOL4L_HUMAN__Q96MY1 RecName: Full=Nucleolar protein 4-like;
MSDSTWMSADPHLASSLSPSQDERMRSPQNLHSQEDDDSSSESGSGNGSSTLNPSTSSSTQGDPAFPEMNGNGAVAPMDFTTAAEDQPINLCDKLPPATALGTASYPSDGCGADGLRSRVKYGVKTTPESPPYSSGSYDSIKTEVSGCPEDLTVGRAPTADDDDDDHDDHEDNDKMNDSEGMDPERLKAFNMFVRLFVDENLDRMVPISKQPKEKIQAIIESCSRQFPEFQERARKRIRTYLKSCRRMKKNGMEMTRPTPPHLTSAMAENILAAACESETRKAAKRMRLEIYQSSQDEPIALDKQHSRDSAAITHSTYSLPASSYSQDPVYANGGLNYSYRGYGALSSNLQPPASLQTGNHSNGPTDLSMKGGASTTSTTPTPTPSSTSTSRPVPTAQLSPTEISAVRQLIAGYRESAAFLLRSADELENLILQQN
>NRIP1_HUMAN__P48552 RecName: Full=Nuclear receptor-interacting protein 1; AltName: Full=Nuclear factor RIP140; AltName: Full=Receptor-interacting protein 140;
MTHGEELGSDVHQDSIVLTYLEGLLMHQAAGGSGTAVDKKSAGHNEEDQNFNISGSAFPTCQSNGPVLNTHTYQGSGMLHLKKARLLQSSEDWNAAKRKRLSDSIMNLNVKKEALLAGMVDSVPKGKQDSTLLASLLQSFSSRLQTVALSQQIRQSLKEQGYALSHDSLKVEKDLRCYGVASSHLKTLLKKSKVKDQKPDTNLPDVTKNLIRDRFAESPHHVGQSGTKVMSEPLSCAARLQAVASMVEKRASPATSPKPSVACSQLALLLSSEAHLQQYSREHALKTQNANQAASERLAAMARLQENGQKDVGSYQLPKGMSSHLNGQARTSSSKLMASKSSATVFQNPMGIIPSSPKNAGYKNSLERNNIKQAANNSLLLHLLKSQTIPKPMNGHSHSERGSIFEESSTPTTIDEYSDNNPSFTDDSSGDESSYSNCVPIDLSCKHRTEKSESDQPVSLDNFTQSLLNTWDPKVPDVDIKEDQDTSKNSKLNSHQKVTLLQLLLGHKNEENVEKNTSPQGVHNDVSKFNTQNYARTSVIESPSTNRTTPVSTPPLLTSSKAGSPINLSQHSLVIKWNSPPYVCSTQSEKLTNTASNHSMDLTKSKDPPGEKPAQNEGAQNSATFSASKLLQNLAQCGMQSSMSVEEQRPSKQLLTGNTDKPIGMIDRLNSPLLSNKTNAVEENKAFSSQPTGPEPGLSGSEIENLLERRTVLQLLLGNPNKGKSEKKEKTPLRDESTQEHSERALSEQILMVKIKSEPCDDLQIPNTNVHLSHDAKSAPFLGMAPAVQRSAPALPVSEDFKSEPVSPQDFSFSKNGLLSRLLRQNQDSYLADDSDRSHRNNEMALLESKNLCMVPKKRKLYTEPLENPFKKMKNNIVDAANNHSAPEVLYGSLLNQEELKFSRNDLEFKYPAGHGSASESEHRSWARESKSFNVLKQLLLSENCVRDLSPHRSNSVADSKKKGHKNNVTNSKPEFSISSLNGLMYSSTQPSSCMDNRTFSYPGVVKTPVSPTFPEHLGCAGSRPESGLLNGCSMPSEKGPIKWVITDAEKNEYEKDSPRLTKTNPILYYMLQKGGNSVTSRETQDKDIWREASSAESVSQVTAKEELLPTAETKASFFNLRSPYNSHMGNNASRPHSANGEVYGLLGSVLTIKKESE
>RBBP5_HUMAN__Q15291 RecName: Full=Retinoblastoma-binding protein 5; Short=RBBP-5; AltName: Full=Retinoblastoma-binding protein RBQ-3;
MNLELLESFGQNYPEEADGTLDCISMALTCTFNRWGTLLAVGCNDGRIVIWDFLTRGIAKIISAHIHPVCSLCWSRDGHKLVSASTDNIVSQWDVLSGDCDQRFRFPSPILKVQYHPRDQNKVLVCPMKSAPVMLTLSDSKHVVLPVDDDSDLNVVASFDRRGEYIYTGNAKGKILVLKTDSQDLVASFRVTTGTSNTTAIKSIEFARKGSCFLINTADRIIRVYDGREILTCGRDGEPEPMQKLQDLVNRTPWKKCCFSGDGEYIVAGSARQHALYIWEKSIGNLVKILHGTRGELLLDVAWHPVRPIIASISSGVVSIWAQNQVENWSAFAPDFKELDENVEYEERESEFDIEDEDKSEPEQTGADAAEDEEVDVTSVDPIAAFCSSDEELEDSKALLYLPIAPEVEDPEENPYGPPPDAVQTSLMDEGASSEKKRQSSADGSQPPKKKPKTTNIELQGVPNDEVHPLLGVKGDGKSKKKQAGRPKGSKGKEKDSPFKPKLYKGDRGLPLEGSAKGKVQAELSQPLTAGGAISELL
>SOBP_HUMAN__A7XYQ1 RecName: Full=Sine oculis-binding protein homolog; AltName: Full=Jackson circler protein 1;
MAEMEKEGRPPENKRSRKPAHPVKREINEEMKNFAENTMNELLGWYGYDKVELKDGEDIEFRSYPTDGESRQHISVLKENSLPKPKLPEDSVISPYNISTGYSGLATGNGLSDSPAGSKDHGSVPIIVPLIPPPFIKPPAEDDVSNVQIMCAWCQKVGIKRYSLSMGSEVKSFCSEKCFAACRRAYFKRNKARDEDGHAENFPQQHYAKETPRLAFKNNCELLVCDWCKHIRHTKEYLDFGDGERRLQFCSAKCLNQYKMDIFYKETQANLPAGLCSTLHPPMENKAEGTGVQLLTPDSWNIPLTDARRKAPSPVATAGQSQGPGPSASTTVSPSDTANCSVTKIPTPVPKSIPISETPNIPPVSVQPPASIGPPLGVPPRSPPMVMTNRGPVPLPIFMEQQIMQQIRPPFIRGPPHHASNPNSPLSNPMLPGIGPPPGGPRNLGPTSSPMHRPMLSPHIHPPSTPTMPGNPPGLLPPPPPGAPLPSLPFPPVSMMPNGPMPVPQMMNFGLPSLAPLVPPPTLLVPYPVIVPLPVPIPIPIPIPHVSDSKPPNGFSSNGENFIPNAPGDSAAAGGKPSGHSLSPRDSKQGSSKSADSPPGCSGQALSLAPTPAEHGRSEVVDLTRRAGSPPGPPGAGGQLGFPGVLQGPQDGVIDLTVGHRARLHNVIHRALHAHVKAEREPSAAERRTCGGCRDGHCSPPAAGDPGPGAPAGPEAAAACNVIVNGTRGAAAEGAKSAEPPPEQPPPPPPPAPPKKLLSPEEPAVSELESVKENNCASNCHLDGEAAKKLMGEEALAGGDKSDPNLNNPADEDHAYALRMLPKTGCVIQPVPKPAEKAAMAPCIISSPMLSAGPEDLEPPLKRRCLRIRNQNK
>ZN219_HUMAN__Q9P2Y4 RecName: Full=Zinc finger protein 219;
MEGSRPRAPSGHLAPSPPAFDGELDLQRYSNGPAVSAGSLGMGAVSWSESRAGERRFPCPVCGKRFRFNSILALHLRAHPGAQAFQCPHCGHRAAQRALLRSHLRTHQPERPRSPAARLLLELEERALLREARLGRARSSGGMQATPATEGLARPQAPSSSAFRCPYCKGKFRTSAERERHLHILHRPWKCGLCSFGSSQEEELLHHSLTAHGAPERPLAATSAAPPPQPQPQPPPQPEPRSVPQPEPEPEPEREATPTPAPAAPEEPPAPPEFRCQVCGQSFTQSWFLKGHMRKHKASFDHACPVCGRCFKEPWFLKNHMKVHASKLGPLRAPGPASGPARAPQPPDLGLLAYEPLGPALLLAPAPTPAERREPPSLLGYLSLRAGEGRPNGEGAEPGPGRSFGGFRPLSSALPARARRHRAEEPEEEEEVVEAEEETWARGRSLGSLASLHPRPGEGPGHSASAAGAQARSTATQEENGLLVGGTRPEGGRGATGKDCPFCGKSFRSAHHLKVHLRVHTGERPYKCPHCDYAGTQSGSLKYHLQRHHREQRSGAGPGPPPEPPPPSQRGSAPQSGAKPSPQPATWVEGASSPRPPSSGAGPGSRRKPASPGRTLRNGRGGEAEPLDLSLRAGPGGEAGPGGALHRCLFCPFATGAPELMALHLQVHHSRRARGRRPPQADASPPYARVPSGETPPSPSQEGEEGSGLSRPGEAGLGGQER
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ID ATX1L_HUMAN Reviewed; 689 AA.
AC P0C7T5;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 1.
DT 11-NOV-2015, entry version 66.
DE RecName: Full=Ataxin-1-like;
DE AltName: Full=Brother of ataxin-1;
DE Short=Brother of ATXN1;
GN Name=ATXN1L; Synonyms=BOAT, BOAT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP INTERACTION WITH NCOR2 AND ATXN1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=16121196; DOI=10.1038/sj.emboj.7600785;
RA Mizutani A., Wang L., Rajan H., Vig P.J.S., Alaynick W.A.,
RA Thaler J.P., Tsai C.-C.;
RT "Boat, an AXH domain protein, suppresses the cytotoxicity of mutant
RT ataxin-1.";
RL EMBO J. 24:3339-3351(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [5]
RP FUNCTION, AND INTERACTION WITH RBPJ.
RX PubMed=21475249; DOI=10.1038/embor.2011.49;
RA Tong X., Gui H., Jin F., Heck B.W., Lin P., Ma J., Fondell J.D.,
RA Tsai C.C.;
RT "Ataxin-1 and Brother of ataxin-1 are components of the Notch
RT signalling pathway.";
RL EMBO Rep. 12:428-435(2011).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Chromatin-binding factor that repress Notch signaling in
CC the absence of Notch intracellular domain by acting as a CBF1
CC corepressor. Binds to the HEY promoter and might assist, along
CC with NCOR2, RBPJ-mediated repression. Can suppress ATXN1
CC cytotoxicity in spinocerebellar ataxia type 1 (SCA1) (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with CIC (By similarity). Interacts
CC (via AXH domain) with NCOR2. Interacts with ATXN1. Directly
CC interacts with RBPJ; this interaction is disrupted in the presence
CC of Notch intracellular domain. Competes with ATXN1 for RBPJ-
CC binding. {ECO:0000250, ECO:0000269|PubMed:16121196,
CC ECO:0000269|PubMed:21475249}.
CC -!- INTERACTION:
CC Q06330:RBPJ; NbExp=7; IntAct=EBI-8624731, EBI-632552;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16121196}. Cell
CC projection, dendrite {ECO:0000269|PubMed:16121196}. Note=Forms
CC nuclear foci. Colocalizes with NCOR2 and HDAC3. Distributed beyond
CC the nucleus into the cell body and dendrites in Purkinje cells and
CC in inferior olive cells.
CC -!- TISSUE SPECIFICITY: Expressed in cerebellum and cerebral cortex.
CC {ECO:0000269|PubMed:16121196}.
CC -!- SIMILARITY: Belongs to the ATXN1 family. {ECO:0000305}.
CC -!- SIMILARITY: Contains 1 AXH domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00496}.
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DR EMBL; AC010653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX537575; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS45523.1; -.
DR RefSeq; NP_001131147.1; NM_001137675.3.
DR UniGene; Hs.743239; -.
DR ProteinModelPortal; P0C7T5; -.
DR SMR; P0C7T5; 468-582.
DR BioGrid; 131172; 67.
DR IntAct; P0C7T5; 4.
DR MINT; MINT-8176805; -.
DR STRING; 9606.ENSP00000415822; -.
DR PhosphoSite; P0C7T5; -.
DR DMDM; 206557834; -.
DR MaxQB; P0C7T5; -.
DR PaxDb; P0C7T5; -.
DR PRIDE; P0C7T5; -.
DR Ensembl; ENST00000427980; ENSP00000415822; ENSG00000224470.
DR GeneID; 342371; -.
DR KEGG; hsa:342371; -.
DR UCSC; uc002fbd.3; human.
DR CTD; 342371; -.
DR GeneCards; ATXN1L; -.
DR H-InvDB; HIX0013220; -.
DR HGNC; HGNC:33279; ATXN1L.
DR MIM; 614301; gene.
DR neXtProt; NX_P0C7T5; -.
DR PharmGKB; PA162377321; -.
DR eggNOG; KOG4053; Eukaryota.
DR eggNOG; ENOG410XSNX; LUCA.
DR GeneTree; ENSGT00390000005939; -.
DR HOGENOM; HOG000034225; -.
DR HOVERGEN; HBG100955; -.
DR InParanoid; P0C7T5; -.
DR OMA; TSCSTNH; -.
DR OrthoDB; EOG7PGDQ2; -.
DR PhylomeDB; P0C7T5; -.
DR TreeFam; TF350643; -.
DR ChiTaRS; ATXN1L; human.
DR GenomeRNAi; 342371; -.
DR NextBio; 98271; -.
DR PRO; PR:P0C7T5; -.
DR Proteomes; UP000005640; Chromosome 16.
DR Bgee; P0C7T5; -.
DR CleanEx; HS_ATXN1L; -.
DR Genevisible; P0C7T5; HS.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR Gene3D; 2.170.16.10; -; 1.
DR InterPro; IPR013723; Ataxin-1_HBP1.
DR InterPro; IPR028992; Hedgehog/Intein_dom.
DR Pfam; PF08517; AXH; 1.
DR SUPFAM; SSF102031; SSF102031; 1.
DR PROSITE; PS51148; AXH; 1.
PE 1: Evidence at protein level;
KW Cell projection; Complete proteome; DNA-binding; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1 689 Ataxin-1-like.
FT /FTId=PRO_0000343709.
FT DOMAIN 457 588 AXH. {ECO:0000255|PROSITE-
FT ProRule:PRU00496}.
FT REGION 20 197 Interaction with NCOR2 and ATXN1.
FT REGION 20 197 Self-association.
FT COMPBIAS 88 256 Pro-rich.
FT MOD_RES 284 284 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 361 361 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT VARIANT 313 313 S -> P (in dbSNP:rs7194407).
FT /FTId=VAR_044496.
SQ SEQUENCE 689 AA; 73306 MW; 9C5D3938EF91F2C7 CRC64;
MKPVHERSQE CLPPKKRDLP VTSEDMGRTT SCSTNHTPSS DASEWSRGVV VAGQSQAGAR
VSLGGDGAEA ITGLTVDQYG MLYKVAVPPA TFSPTGLPSV VNMSPLPPTF NVASSLIQHP
GIHYPPLHYA QLPSTSLQFI GSPYSLPYAV PPNFLPSPLL SPSANLATSH LPHFVPYASL
LAEGATPPPQ APSPAHSFNK APSATSPSGQ LPHHSSTQPL DLAPGRMPIY YQMSRLPAGY
TLHETPPAGA SPVLTPQESQ SALEAAAANG GQRPRERNLV RRESEALDSP NSKGEGQGLV
PVVECVVDGQ LFSGSQTPRV EVAAPAHRGT PDTDLEVQRV VGALASQDYR VVAAQRKEEP
SPLNLSHHTP DHQGEGRGSA RNPAELAEKS QARGFYPQSH QEPVKHRPLP KAMVVANGNL
VPTGTDSGLL PVGSEILVAS SLDVQARATF PDKEPTPPPI TSSHLPSHFM KGAIIQLATG
ELKRVEDLQT QDFVRSAEVS GGLKIDSSTV VDIQESQWPG FVMLHFVVGE QQSKVSIEVP
PEHPFFVYGQ GWSSCSPGRT TQLFSLPCHR LQVGDVCISI SLQSLNSNSV SQASCAPPSQ
LGPPRERPER TVLGSRELCD SEGKSQPAGE GSRVVEPSQP ESGAQACWPA PSFQRYSMQG
EEARAALLRP SFIPQEVKLS IEGRSNAGK
//
ID BRCA1_HUMAN Reviewed; 1863 AA.
AC P38398; E9PFZ0; O15129; Q1RMC1; Q3LRJ0; Q3LRJ6; Q6IN79; Q7KYU9;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 11-NOV-2015, entry version 209.
DE RecName: Full=Breast cancer type 1 susceptibility protein;
DE EC=6.3.2.-;
DE AltName: Full=RING finger protein 53;
GN Name=BRCA1; Synonyms=RNF53;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT BC ARG-1775.
RX PubMed=7545954; DOI=10.1126/science.7545954;
RA Miki Y., Swensen J., Shattuck-Eidens D., Futreal P.A., Harshman K.,
RA Tavtigian S., Liu Q., Cochran C., Bennett L.M., Ding W., Bell R.,
RA Rosenthal J., Hussey C., Tran T., McClure M., Frye C., Hattier T.,
RA Phelps R., Haugen-Strano A., Katcher H., Yakumo K., Gholami Z.,
RA Shaffer D., Stone S., Bayer S., Wray C., Bogden R., Dayananth P.,
RA Ward J., Tonin P., Narod S., Bristow P.K., Norris F.H., Helvering L.,
RA Morrison P., Rosteck P., Lai M., Barrett J.C., Lewis C., Neuhausen S.,
RA Cannon-Albright L., Godlgar D., Wiseman R., Kamb A., Skolnick M.H.;
RT "A strong candidate for the breast and ovarian cancer susceptibility
RT gene BRCA1.";
RL Science 266:66-71(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8938427; DOI=10.1101/gr.6.11.1029;
RA Smith T.M., Lee M.K., Szabo C.I., Jerome N., McEuen M., Taylor M.,
RA Hood L., King M.-C.;
RT "Complete genomic sequence and analysis of 117 kb of human DNA
RT containing the gene BRCA1.";
RL Genome Res. 6:1029-1049(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM
RP 2), VARIANTS ARG-239 AND GLY-1613, AND TISSUE SPECIFICITY (ISOFORMS 1
RP AND 3).
RC TISSUE=Mammary gland;
RX PubMed=9010228; DOI=10.1038/sj.onc.1200924;
RA Wilson C.A., Payton M.N., Elliott G.S., Buaas F.W., Cajulis E.E.,
RA Grosshans D., Ramos L., Reese D.M., Slamon D.J., Calzone F.J.;
RT "Differential subcellular localization, expression and biological
RT toxicity of BRCA1 and the splice variant BRCA1-delta11b.";
RL Oncogene 14:1-16(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RA Holt J.T., Robinson-Benion C.;
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-356.
RA Raymond C.K., Paddock M., Subramanian S., Deodato C., Zhou Y.,
RA Haugen E., Kaul R., Olson M.V.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-275; ARG-356;
RP ASN-693; LEU-871; GLY-1038; ASN-1040; GLY-1140; ARG-1183; GLY-1613 AND
RP ALA-1620.
RG NIEHS SNPs program;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 7), AND
RP VARIANTS LEU-871; GLY-1038; ARG-1183; GLY-1613 AND ILE-1652.
RC TISSUE=PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 6-18 (ISOFORM 1), PROTEIN SEQUENCE OF 18-26
RP (ISOFORM 4), AND ALTERNATIVE INITIATION (ISOFORM 4).
RX PubMed=10851077; DOI=10.1038/sj.onc.1203599;
RA Liu J., Prolla G., Rostagno A., Chiarle R., Feiner H., Inghirami G.;
RT "Initiation of translation from a downstream in-frame AUG codon on
RT BRCA1 can generate the novel isoform protein DeltaBRCA1(17aa).";
RL Oncogene 19:2767-2773(2000).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORM 5), AND SUBCELLULAR LOCATION (ISOFORM
RP 5).
RX PubMed=8972225;
RA Thakur S., Zhang H.B., Peng Y., Le H., Carroll B., Ward T., Yao J.,
RA Farid L.M., Couch F.J., Wilson R.B., Weber B.L.;
RT "Localization of BRCA1 and a splice variant identifies the nuclear
RT localization signal.";
RL Mol. Cell. Biol. 17:444-452(1997).
RN [11]
RP INTERACTION WITH BAP1, SUBCELLULAR LOCATION, VARIANTS GLY-61 AND
RP GLY-64, AND MUTAGENESIS OF ARG-71.
RX PubMed=9528852; DOI=10.1038/sj.onc.1201861;
RA Jensen D.E., Proctor M., Marquis S.T., Gardner H.P., Ha S.I.,
RA Chodosh L.A., Ishov A.M., Tommerup N., Vissing H., Sekido Y.,
RA Minna J., Borodovsky A., Schultz D.C., Wilkinson K.D., Maul G.G.,
RA Barlev N., Berger S., Prendergast G.C., Rauscher F.J. III;
RT "BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING
RT finger and enhances BRCA1-mediated cell growth suppression.";
RL Oncogene 16:1097-1112(1998).
RN [12]
RP INTERACTION WITH RBBP8.
RX PubMed=9811458; DOI=10.1038/sj.onc.1202150;
RA Wong A.K., Ormonde P.A., Pero R., Chen Y., Lian L., Salada G.,
RA Berry S., Lawrence Q., Dayananth P., Ha P., Tavtigian S.V., Teng D.H.,
RA Bartel P.L.;
RT "Characterization of a carboxy-terminal BRCA1 interacting protein.";
RL Oncogene 17:2279-2285(1998).
RN [13]
RP FUNCTION AS AN E2-DEPENDENT UBIQUITIN-PROTEIN LIGASE.
RX PubMed=10500182; DOI=10.1073/pnas.96.20.11364;
RA Lorick K.L., Jensen J.P., Fang S., Ong A.M., Hatakeyama S.,
RA Weissman A.M.;
RT "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent
RT ubiquitination.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:11364-11369(1999).
RN [14]
RP IDENTIFICATION IN THE BASC COMPLEX.
RX PubMed=10783165; DOI=10.1101/gad.827000;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [15]
RP PHOSPHORYLATION AT SER-1143; SER-1280; SER-1387; THR-1394; SER-1423
RP AND SER-1457, MUTAGENESIS OF SER-1143; SER-1239; SER-1280; SER-1298;
RP SER-1330; SER-1387; THR-1394; SER-1423; SER-1457; SER-1466; SER-1524
RP AND SER-1755, AND CHARACTERIZATION OF VARIANT BC ALA-1720.
RX PubMed=11114888; DOI=10.1101/gad.851000;
RA Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D.,
RA Elledge S.J., Abraham R.T.;
RT "Functional interactions between BRCA1 and the checkpoint kinase ATR
RT during genotoxic stress.";
RL Genes Dev. 14:2989-3002(2000).
RN [16]
RP FUNCTION IN DNA DAMAGE RESPONSE, PHOSPHORYLATION AT SER-988 BY CHEK2,
RP AND INTERACTION WITH CHEK2.
RX PubMed=10724175; DOI=10.1038/35004614;
RA Lee J.S., Collins K.M., Brown A.L., Lee C.H., Chung J.H.;
RT "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage
RT response.";
RL Nature 404:201-204(2000).
RN [17]
RP INTERACTION WITH BRIP1, CHARACTERIZATION OF VARIANT OVARIAN CANCER
RP ARG-1749, AND CHARACTERIZATION OF VARIANT BC ARG-1775.
RX PubMed=11301010; DOI=10.1016/S0092-8674(01)00304-X;
RA Cantor S.B., Bell D.W., Ganesan S., Kass E.M., Drapkin R.,
RA Grossman S., Wahrer D.C.R., Sgroi D.C., Lane W.S., Haber D.A.,
RA Livingston D.M.;
RT "BACH1, a novel helicase-like protein, interacts directly with BRCA1
RT and contributes to its DNA repair function.";
RL Cell 105:149-160(2001).
RN [18]
RP INTERACTION WITH NELFB.
RX PubMed=11739404; DOI=10.1083/jcb.200108049;
RA Ye Q., Hu Y.-F., Zhong H., Nye A.C., Belmont A.S., Li R.;
RT "BRCA1-induced large-scale chromatin unfolding and allele-specific
RT effects of cancer-predisposing mutations.";
RL J. Cell Biol. 155:911-921(2001).
RN [19]
RP INTERACTION WITH FANCD2.
RX PubMed=11239454; DOI=10.1016/S1097-2765(01)00173-3;
RA Garcia-Higuera I., Taniguchi T., Ganesan S., Meyn M.S., Timmers C.,
RA Hejna J., Grompe M., D'Andrea A.D.;
RT "Interaction of the Fanconi anemia proteins and BRCA1 in a common
RT pathway.";
RL Mol. Cell 7:249-262(2001).
RN [20]
RP PHOSPHORYLATION BY ATM, AND MUTAGENESIS OF SER-1387; SER-1423 AND
RP SER-1524.
RX PubMed=12183412;
RA Xu B., O'Donnell A.H., Kim S.-T., Kastan M.B.;
RT "Phosphorylation of serine 1387 in BRCA1 is specifically required for
RT the Atm-mediated S-phase checkpoint after ionizing irradiation.";
RL Cancer Res. 62:4588-4591(2002).
RN [21]
RP INTERACTION WITH H2AFX.
RX PubMed=12419185; DOI=10.1016/S0960-9822(02)01259-9;
RA Kobayashi J., Tauchi H., Sakamoto S., Nakamura A., Morishima K.,
RA Matsuura S., Kobayashi T., Tamai K., Tanimoto K., Komatsu K.;
RT "NBS1 localizes to gamma-H2AX foci through interaction with the
RT FHA/BRCT domain.";
RL Curr. Biol. 12:1846-1851(2002).
RN [22]
RP INTERACTION WITH SMC1A.
RX PubMed=11877377; DOI=10.1101/gad.970702;
RA Yazdi P.T., Wang Y., Zhao S., Patel N., Lee E.Y.-H.P., Qin J.;
RT "SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-
RT phase checkpoint.";
RL Genes Dev. 16:571-582(2002).
RN [23]
RP INTERACTION WITH LMO4.
RX PubMed=11751867; DOI=10.1074/jbc.M110603200;
RA Sum E.Y., Peng B., Yu X., Chen J., Byrne J., Lindeman G.J.,
RA Visvader J.E.;
RT "The LIM domain protein LMO4 interacts with the cofactor CtIP and the
RT tumor suppressor BRCA1 and inhibits BRCA1 activity.";
RL J. Biol. Chem. 277:7849-7856(2002).
RN [24]
RP FUNCTION, AND INTERACTION WITH CHEK1.
RX PubMed=11836499; DOI=10.1038/ng837;
RA Yarden R.I., Pardo-Reoyo S., Sgagias M., Cowan K.H., Brody L.C.;
RT "BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon
RT DNA damage.";
RL Nat. Genet. 30:285-289(2002).
RN [25]
RP INTERACTION WITH ACACA.
RX PubMed=12360400; DOI=10.1038/sj.onc.1205915;
RA Magnard C., Bachelier R., Vincent A., Jaquinod M., Kieffer S.,
RA Lenoir G.M., Venezia N.D.;
RT "BRCA1 interacts with acetyl-CoA carboxylase through its tandem of
RT BRCT domains.";
RL Oncogene 21:6729-6739(2002).
RN [26]
RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH BARD1.
RX PubMed=12890688; DOI=10.1074/jbc.C300249200;
RA Wu-Baer F., Lagrazon K., Yuan W., Baer R.;
RT "The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an
RT unconventional linkage involving lysine residue K6 of ubiquitin.";
RL J. Biol. Chem. 278:34743-34746(2003).
RN [27]
RP FUNCTION.
RX PubMed=12887909; DOI=10.1016/S1097-2765(03)00281-8;
RA Vandenberg C.J., Gergely F., Ong C.Y., Pace P., Mallery D.L., Hiom K.,
RA Patel K.J.;
RT "BRCA1-independent ubiquitination of FANCD2.";
RL Mol. Cell 12:247-254(2003).
RN [28]
RP INTERACTION WITH BRCC3.
RX PubMed=14636569; DOI=10.1016/S1097-2765(03)00424-6;
RA Dong Y., Hakimi M.-A., Chen X., Kumaraswamy E., Cooch N.S.,
RA Godwin A.K., Shiekhattar R.;
RT "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2,
RT by a signalosome-like subunit and its role in DNA repair.";
RL Mol. Cell 12:1087-1099(2003).
RN [29]
RP FUNCTION, AND INTERACTION WITH BARD1.
RX PubMed=14976165; DOI=10.1093/hmg/ddh095;
RA Morris J.R., Solomon E.;
RT "BRCA1:BARD1 induces the formation of conjugated ubiquitin structures,
RT dependent on K6 of ubiquitin, in cells during DNA replication and
RT repair.";
RL Hum. Mol. Genet. 13:807-817(2004).
RN [30]
RP INTERACTION WITH AURKA, FUNCTION, MUTAGENESIS OF SER-308, AND
RP PHOSPHORYLATION AT SER-308.
RX PubMed=14990569; DOI=10.1074/jbc.M311780200;
RA Ouchi M., Fujiuchi N., Sasai K., Katayama H., Minamishima Y.A.,
RA Ongusaha P.P., Deng C., Sen S., Lee S.W., Ouchi T.;
RT "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M
RT transition.";
RL J. Biol. Chem. 279:19643-19648(2004).
RN [31]
RP INTERACTION WITH DCLRE1C.
RX PubMed=15456891; DOI=10.1128/MCB.24.20.9207-9220.2004;
RA Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D.,
RA Legerski R.J.;
RT "Artemis is a phosphorylation target of ATM and ATR and is involved in
RT the G2/M DNA damage checkpoint response.";
RL Mol. Cell. Biol. 24:9207-9220(2004).
RN [32]
RP INTERACTION WITH CLSPN.
RX PubMed=15096610; DOI=10.1073/pnas.0401847101;
RA Lin S.-Y., Li K., Stewart G.S., Elledge S.J.;
RT "Human claspin works with BRCA1 to both positively and negatively
RT regulate cell proliferation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6484-6489(2004).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1336, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [34]
RP FUNCTION, INTERACTION WITH RBBP8, AND MUTAGENESIS OF ILE-26.
RX PubMed=16818604; DOI=10.1101/gad.1431006;
RA Yu X., Fu S., Lai M., Baer R., Chen J.;
RT "BRCA1 ubiquitinates its phosphorylation-dependent binding partner
RT CtIP.";
RL Genes Dev. 20:1721-1726(2006).
RN [35]
RP FUNCTION, AND INTERACTION WITH ACACA.
RX PubMed=16326698; DOI=10.1074/jbc.M504652200;
RA Moreau K., Dizin E., Ray H., Luquain C., Lefai E., Foufelle F.,
RA Billaud M., Lenoir G.M., Venezia N.D.;
RT "BRCA1 affects lipid synthesis through its interaction with acetyl-CoA
RT carboxylase.";
RL J. Biol. Chem. 281:3172-3181(2006).
RN [36]
RP INTERACTION WITH ACACA.
RX PubMed=16698035; DOI=10.1016/j.jmb.2006.04.010;
RA Ray H., Moreau K., Dizin E., Callebaut I., Venezia N.D.;
RT "ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.";
RL J. Mol. Biol. 359:973-982(2006).
RN [37]
RP FUNCTION, PHOSPHORYLATION BY AURKA, AND ENZYME REGULATION.
RX PubMed=18056443; DOI=10.1158/0008-5472.CAN-07-2578;
RA Sankaran S., Crone D.E., Palazzo R.E., Parvin J.D.;
RT "Aurora-A kinase regulates breast cancer associated gene 1 inhibition
RT of centrosome-dependent microtubule nucleation.";
RL Cancer Res. 67:11186-11194(2007).
RN [38]
RP INTERACTION WITH FAM175A.
RX PubMed=17643122; DOI=10.1038/nsmb1277;
RA Kim H., Huang J., Chen J.;
RT "CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA
RT damage response.";
RL Nat. Struct. Mol. Biol. 14:710-715(2007).
RN [39]
RP INTERACTION WITH FAM175A.
RX PubMed=17643121; DOI=10.1038/nsmb1279;
RA Liu Z., Wu J., Yu X.;
RT "CCDC98 targets BRCA1 to DNA damage sites.";
RL Nat. Struct. Mol. Biol. 14:716-720(2007).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [41]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FAM175A.
RX PubMed=17525340; DOI=10.1126/science.1139476;
RA Wang B., Matsuoka S., Ballif B.A., Zhang D., Smogorzewska A., Giyi S.,
RA Elledge S.J.;
RT "Abraxas and RAP80 form a BRCA1 protein complex required for the DNA
RT damage response.";
RL Science 316:1194-1198(2007).
RN [42]
RP INVOLVEMENT IN PNCA4.
RX PubMed=18762988; DOI=10.1007/s00439-008-0554-0;
RA Al-Sukhni W., Rothenmund H., Borgida A.E., Zogopoulos G., O'Shea A.M.,
RA Pollett A., Gallinger S.;
RT "Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.";
RL Hum. Genet. 124:271-278(2008).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395; SER-398; SER-753;
RP SER-1211; SER-1217 AND SER-1218, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [44]
RP FUNCTION, AND IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261748; DOI=10.1101/gad.1770609;
RA Feng L., Huang J., Chen J.;
RT "MERIT40 facilitates BRCA1 localization and DNA damage repair.";
RL Genes Dev. 23:719-728(2009).
RN [45]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261749; DOI=10.1101/gad.1770309;
RA Wang B., Hurov K., Hofmann K., Elledge S.J.;
RT "NBA1, a new player in the Brca1 A complex, is required for DNA damage
RT resistance and checkpoint control.";
RL Genes Dev. 23:729-739(2009).
RN [46]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261746; DOI=10.1101/gad.1739609;
RA Shao G., Patterson-Fortin J., Messick T.E., Feng D., Shanbhag N.,
RA Wang Y., Greenberg R.A.;
RT "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA
RT double-strand breaks.";
RL Genes Dev. 23:740-754(2009).
RN [47]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH PALB2,
RP IDENTIFICATION IN A BRCA COMPLEX WITH BRCA1 AND PALB2, AND
RP CHARACTERIZATION OF VARIANT OVARIAN CANCER 1411-THR.
RX PubMed=19369211; DOI=10.1073/pnas.0811159106;
RA Sy S.M., Huen M.S., Chen J.;
RT "PALB2 is an integral component of the BRCA complex required for
RT homologous recombination repair.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:7155-7160(2009).
RN [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395 AND SER-398, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [49]
RP FUNCTION, INTERACTION WITH CCAR2, AND SUBCELLULAR LOCATION.
RX PubMed=20160719; DOI=10.1038/sj.bjc.6605577;
RA Hiraike H., Wada-Hiraike O., Nakagawa S., Koyama S., Miyamoto Y.,
RA Sone K., Tanikawa M., Tsuruga T., Nagasaka K., Matsumoto Y., Oda K.,
RA Shoji K., Fukuhara H., Saji S., Nakagawa K., Kato S., Yano T.,
RA Taketani Y.;
RT "Identification of DBC1 as a transcriptional repressor for BRCA1.";
RL Br. J. Cancer 102:1061-1067(2010).
RN [50]
RP FUNCTION, INTERACTION WITH BARD1 AND UBXN1, UBIQUITINATION, AND
RP MUTAGENESIS OF ILE-26.
RX PubMed=20351172; DOI=10.1128/MCB.01056-09;
RA Wu-Baer F., Ludwig T., Baer R.;
RT "The UBXN1 protein associates with autoubiquitinated forms of the
RT BRCA1 tumor suppressor and inhibits its enzymatic function.";
RL Mol. Cell. Biol. 30:2787-2798(2010).
RN [51]
RP FUNCTION IN CHROMOSOMAL STABILITY, AND PHOSPHORYLATION AT SER-988 BY
RP CHEK2.
RX PubMed=20364141; DOI=10.1038/ncb2051;
RA Stolz A., Ertych N., Kienitz A., Vogel C., Schneider V., Fritz B.,
RA Jacob R., Dittmar G., Weichert W., Petersen I., Bastians H.;
RT "The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal
RT stability in human somatic cells.";
RL Nat. Cell Biol. 12:492-499(2010).
RN [52]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-423; SER-694;
RP SER-1328; SER-1336 AND SER-1342, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [53]
RP PHOSPHORYLATION AT SER-1524, AND SUBCELLULAR LOCATION.
RX PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005;
RA Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y.,
RA Jun J.Y., You H.J.;
RT "Protein phosphatase 5 is necessary for ATR-mediated DNA repair.";
RL Biochem. Biophys. Res. Commun. 404:476-481(2011).
RN [54]
RP INTERACTION WITH KIAA0101.
RX PubMed=21673012; DOI=10.1158/1541-7786.MCR-10-0503;
RA Kais Z., Barsky S.H., Mathsyaraja H., Zha A., Ransburgh D.J., He G.,
RA Pilarski R.T., Shapiro C.L., Huang K., Parvin J.D.;
RT "KIAA0101 interacts with BRCA1 and regulates centrosome number.";
RL Mol. Cancer Res. 9:1091-1099(2011).
RN [55]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-1218; SER-1336
RP AND SER-1342, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [56]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [57]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339; LYS-459; LYS-583;
RP LYS-654; LYS-734 AND LYS-739, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [58]
RP STRUCTURE BY NMR OF 1-110 IN COMPLEX WITH ZINC IONS AND BARD1, AND
RP SUBUNIT.
RX PubMed=11573085; DOI=10.1038/nsb1001-833;
RA Brzovic P.S., Rajagopal P., Hoyt D.W., King M.C., Klevit R.E.;
RT "Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.";
RL Nat. Struct. Biol. 8:833-837(2001).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1646-1859, PARTIAL PROTEIN
RP SEQUENCE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11573086; DOI=10.1038/nsb1001-838;
RA Williams R.S., Green R., Glover J.N.;
RT "Crystal structure of the BRCT repeat region from the breast cancer-
RT associated protein BRCA1.";
RL Nat. Struct. Biol. 8:838-842(2001).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1646-1859 OF VARIANT BC
RP ARG-1775, CHARACTERIZATION OF VARIANT BC ARG-1775, AND CIRCULAR
RP DICHROISM.
RX PubMed=12427738; DOI=10.1074/jbc.M210019200;
RA Williams R.S., Glover J.N.;
RT "Structural consequences of a cancer-causing BRCA1-BRCT missense
RT mutation.";
RL J. Biol. Chem. 278:2630-2635(2003).
RN [61]
RP STRUCTURE BY NMR OF 1755-1863.
RX PubMed=15609993; DOI=10.1021/bi049550q;
RA Gaiser O.J., Ball L.J., Schmieder P., Leitner D., Strauss H., Wahl M.,
RA Kuhne R., Oschkinat H., Heinemann U.;
RT "Solution structure, backbone dynamics, and association behavior of
RT the C-terminal BRCT domain from the breast cancer-associated protein
RT BRCA1.";
RL Biochemistry 43:15983-15995(2004).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1649-1859 IN COMPLEX WITH
RP WITH PHOSPHORYLATED BRIP1 PEPTIDE, MUTAGENESIS OF SER-1655; LYS-1702
RP AND GLY-1738, CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749,
RP CHARACTERIZATION OF VARIANT BC ARG-1775, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH PHOSPHORYLATED BRIP1.
RX PubMed=15133502; DOI=10.1038/nsmb775;
RA Clapperton J.A., Manke I.A., Lowery D.M., Ho T., Haire L.F.,
RA Yaffe M.B., Smerdon S.J.;
RT "Structure and mechanism of BRCA1 BRCT domain recognition of
RT phosphorylated BACH1 with implications for cancer.";
RL Nat. Struct. Mol. Biol. 11:512-518(2004).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP PHOSPHORYLATED RBBP8 PEPTIDE, AND SUBUNIT.
RX PubMed=16101277; DOI=10.1021/bi0509651;
RA Varma A.K., Brown R.S., Birrane G., Ladias J.A.;
RT "Structural basis for cell cycle checkpoint control by the BRCA1-CtIP
RT complex.";
RL Biochemistry 44:10941-10946(2005).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP PHOSPHORYLATED ACACA PEPTIDE, AND SUBUNIT.
RX PubMed=18452305; DOI=10.1021/bi800314m;
RA Shen Y., Tong L.;
RT "Structural evidence for direct interactions between the BRCT domains
RT of human BRCA1 and a phospho-peptide from human ACC1.";
RL Biochemistry 47:5767-5773(2008).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 1649-1859 OF VARIANT BC
RP LYS-1775, VARIANT BC LYS-1775, AND CHARACTERIZATION OF VARIANT BC
RP LYS-1775.
RX PubMed=18285836; DOI=10.1038/ejhg.2008.13;
RA Tischkowitz M., Hamel N., Carvalho M.A., Birrane G., Soni A.,
RA van Beers E.H., Joosse S.A., Wong N., Novak D., Quenneville L.A.,
RA Grist S.A., Nederlof P.M., Goldgar D.E., Tavtigian S.V.,
RA Monteiro A.N., Ladias J.A., Foulkes W.D.;
RT "Pathogenicity of the BRCA1 missense variant M1775K is determined by
RT the disruption of the BRCT phosphopeptide-binding pocket: a multi-
RT modal approach.";
RL Eur. J. Hum. Genet. 16:820-832(2008).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP PHOSPHORYLATED PEPTIDES, AND DOMAIN.
RX PubMed=20159462; DOI=10.1016/j.str.2009.12.008;
RA Campbell S.J., Edwards R.A., Glover J.N.;
RT "Comparison of the structures and peptide binding specificities of the
RT BRCT domains of MDC1 and BRCA1.";
RL Structure 18:167-176(2010).
RN [67]
RP REVIEW ON VARIANTS.
RX PubMed=8807330; DOI=10.1002/humu.1380080102;
RA Couch F.J., Weber B.L.;
RT "Mutations and polymorphisms in the familial early-onset breast cancer
RT (BRCA1) gene.";
RL Hum. Mutat. 8:8-18(1996).
RN [68]
RP VARIANT BC ARG-1775, AND VARIANTS LEU-1637 AND GLU-1708.
RX PubMed=7939630; DOI=10.1126/science.7939630;
RA Futreal P.A., Liu Q., Shattuck-Eidens D., Cochran C., Harshman K.,
RA Tavtigian S., Bennett L.M., Haugen-Strano A., Swensen J., Miki Y.,
RA Eddington K., McClure M., Frye C., Weaver-Felhaus J., Ding W.,
RA Gholami Z., Soederkvist P., Terry L., Jhanwar S., Berchuk A.,
RA Iglehart J.D., Marks J., Ballinger D.G., Barrett J.C., Skolnick M.H.,
RA Kamb A., Wiseman R.;
RT "BRCA1 mutations in primary breast and ovarian carcinomas.";
RL Science 266:120-122(1994).
RN [69]
RP VARIANT BC GLY-64, AND VARIANTS ALA-772; ASN-1040 AND GLY-1443.
RX PubMed=7894491; DOI=10.1038/ng1294-387;
RA Castilla L.H., Couch F.J., Erdos M.R., Hoskins K.F., Calzone K.,
RA Garber J.E., Boyd J., Lubin M.B., Deshano M.L., Brody L.C.,
RA Collins F.S., Weber B.L.;
RT "Mutations in the BRCA1 gene in families with early-onset breast and
RT ovarian cancer.";
RL Nat. Genet. 8:387-391(1994).
RN [70]
RP VARIANT BC GLY-61, AND VARIANTS ARG-356; GLY-1038; ASN-1040; ARG-1183
RP AND GLY-1613.
RX PubMed=7894493; DOI=10.1038/ng1294-399;
RA Friedman L.S., Ostermeyer E.A., Szabo C.I., Dowd P., Lynch E.D.,
RA Rowell S.E., King M.-C.;
RT "Confirmation of BRCA1 by analysis of germline mutations linked to
RT breast and ovarian cancer in ten families.";
RL Nat. Genet. 8:399-404(1994).
RN [71]
RP VARIANT BC GLY-61.
RX PubMed=8554067;
RA Serova O., Montagna M., Torchard D., Narod S.A., Tonin P., Sylla B.,
RA Lynch H.T., Feunteun J., Lenoir G.M.;
RT "A high incidence of BRCA1 mutations in 20 breast-ovarian cancer
RT families.";
RL Am. J. Hum. Genet. 58:42-51(1996).
RN [72]
RP VARIANT BROVCA1 TRP-841.
RX PubMed=8968716;
RX DOI=10.1002/(SICI)1098-2272(1996)13:6<595::AID-GEPI5>3.3.CO;2-0;
RA Barker D.F., Almeida E.F.A., Casey G., Fain P.R., Liao S.-Y.,
RA Masunaka I., Noble B., Kurosaki T., Anton-Culver H.;
RT "BRCA1 R841W: a strong candidate for a common mutation with moderate
RT phenotype.";
RL Genet. Epidemiol. 13:595-604(1996).
RN [73]
RP VARIANTS BC AND BROVCA1.
RX PubMed=8776600; DOI=10.1093/hmg/5.6.835;
RA Durocher F., Shattuck-Eidens D., McClure M., Labrie F., Skolnick M.H.,
RA Goldgar D.E., Simard J.;
RT "Comparison of BRCA1 polymorphisms, rare sequence variants and/or
RT missense mutations in unaffected and breast/ovarian cancer
RT populations.";
RL Hum. Mol. Genet. 5:835-842(1996).
RN [74]
RP VARIANTS BC MET-271 AND SER-1150.
RX PubMed=8723683;
RX DOI=10.1002/(SICI)1098-1004(1996)7:4<334::AID-HUMU7>3.3.CO;2-K;
RA Katagiri T., Emi M., Ito I., Kobayashi K., Yoshimoto M., Iwase T.,
RA Kasumi F., Miki Y., Skolnick M.H., Nakamura Y.;
RT "Mutations in the BRCA1 gene in Japanese breast cancer patients.";
RL Hum. Mutat. 7:334-339(1996).
RN [75]
RP VARIANT BC GLY-61, AND VARIANTS ARG-239; TRP-841 AND ILE-1512.
RX PubMed=9760198; DOI=10.1007/s004390050799;
RA Dong J., Chang-Claude J., Wu Y., Schumacher V., Debatin I., Tonin P.,
RA Royer-Pokora B.;
RT "A high proportion of mutations in the BRCA1 gene in German
RT breast/ovarian cancer families with clustering of mutations in the 3'
RT third of the gene.";
RL Hum. Genet. 103:154-161(1998).
RN [76]
RP VARIANT BC GLY-64, AND VARIANTS ALA-772; GLU-820; ASN-1040; GLY-1443;
RP ILE-1512; LEU-1637 AND ILE-1652.
RX PubMed=9482581;
RX DOI=10.1002/(SICI)1098-1004(1998)11:2<166::AID-HUMU10>3.0.CO;2-X;
RA Andersen T.I., Eiken H.G., Couch F., Kaada G., Skrede M., Johnsen H.,
RA Aloysius T.A., Tveit K.M., Tranebjaerg L., Doerum A., Moeller P.,
RA Weber B.L., Boerresen-Dale A.-L.;
RT "Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation
RT screening.";
RL Hum. Mutat. 11:166-174(1998).
RN [77]
RP VARIANTS BC SER-22; LEU-461; ASP-465; VAL-552; SER-892; ASP-960;
RP ILE-1025 AND ALA-1047.
RX PubMed=9609997; DOI=10.1007/s100380050035;
RA Katagiri T., Kasumi F., Yoshimoto M., Nomizu T., Asaishi K., Abe R.,
RA Tsuchiya A., Sugano M., Takai S., Yoneda M., Fukutomi T., Nanba K.,
RA Makita M., Okazaki H., Hirata K., Okazaki M., Furutsuma Y.,
RA Morishita Y., Iino Y., Karino T., Ayabe H., Hara S., Kajiwara T.,
RA Houga S., Shimizu T., Toda M., Yamazaki Y., Uchida T., Kunitomo K.,
RA Sonoo H., Kurebayashi J., Shimotsuma K., Nakamura Y., Miki Y.;
RT "High proportion of missense mutations of the BRCA1 and BRCA2 genes in
RT Japanese breast cancer families.";
RL J. Hum. Genet. 43:42-48(1998).
RN [78]
RP VARIANT OVARIAN CANCER ARG-1749.
RX PubMed=10486320; DOI=10.1086/302583;
RA Gayther S.A., Russell P., Harrington P., Antoniou A.C., Easton D.F.,
RA Ponder B.A.J.;
RT "The contribution of germline BRCA1 and BRCA2 mutations to familial
RT ovarian cancer: no evidence for other ovarian cancer-susceptibility
RT genes.";
RL Am. J. Hum. Genet. 65:1021-1029(1999).
RN [79]
RP VARIANT BC SER-346, AND VARIANTS LEU-871; GLY-1038; ARG-1183 AND
RP GLY-1613.
RX PubMed=10323242; DOI=10.1007/s004390050936;
RA Li S.S.-L., Tseng H.-M., Yang T.-P., Liu C.-H., Teng S.-J.,
RA Huang H.-W., Chen L.-M., Kao H.-W., Chen J.H., Tseng J.-N., Chen A.,
RA Hou M.-F., Huang T.-J., Chang H.-T., Mok K.-T., Tsai J.-H.;
RT "Molecular characterization of germline mutations in the BRCA1 and
RT BRCA2 genes from breast cancer families in Taiwan.";
RL Hum. Genet. 104:201-204(1999).
RN [80]
RP VARIANTS OVARIAN CANCER, AND VARIANTS.
RX PubMed=10196379; DOI=10.1093/hmg/8.5.889;
RA Janezic S.A., Ziogas A., Krumroy L.M., Krasner M., Plummer S.J.,
RA Cohen P., Gildea M., Barker D., Haile R., Casey G., Anton-Culver H.;
RT "Germline BRCA1 alterations in a population-based series of ovarian
RT cancer cases.";
RL Hum. Mol. Genet. 8:889-897(1999).
RN [81]
RP VARIANTS GLY-1347; ILE-1512 AND ILE-1652.
RX PubMed=12215251; DOI=10.1089/10906570260199375;
RA Deffenbaugh A.M., Frank T.S., Hoffman M., Cannon-Albright L.,
RA Neuhausen S.L.;
RT "Characterization of common BRCA1 and BRCA2 variants.";
RL Genet. Test. 6:119-121(2002).
RN [82]
RP VARIANTS ILE-656; LEU-871 AND GLY-1613.
RX PubMed=12442274; DOI=10.1002/humu.9083;
RA Zhi X., Szabo C., Chopin S., Suter N., Wang Q.-S., Ostrander E.A.,
RA Sinilnikova O.M., Lenoir G.M., Goldgar D., Shi Y.-R.;
RT "BRCA1 and BRCA2 sequence variants in Chinese breast cancer
RT families.";
RL Hum. Mutat. 20:474-474(2002).
RN [83]
RP VARIANT BC TYR-749.
RX PubMed=12442275; DOI=10.1002/humu.9084;
RA Ruiz-Flores P., Sinilnikova O.M., Badzioch M.,
RA Calderon-Garciduenas A.L., Chopin S., Fabrice O.,
RA Gonzalez-Guerrero J.F., Szabo C., Lenoir G., Goldgar D.E.,
RA Barrera-Saldana H.A.;
RT "BRCA1 and BRCA2 mutation analysis of early-onset and familial breast
RT cancer cases in Mexico.";
RL Hum. Mutat. 20:474-475(2002).
RN [84]
RP VARIANTS BC GLY-61; LYS-71; GLN-866; TYR-888; ILE-1139; GLY-1210 AND
RP PRO-1297, AND VARIANTS BROVCA1 TYR-835 AND PRO-1786.
RX PubMed=12938098; DOI=10.1002/humu.9174;
RA Meyer P., Voigtlaender T., Bartram C.R., Klaes R.;
RT "Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast
RT and/or ovarian cancer families in Southern Germany.";
RL Hum. Mutat. 22:259-259(2003).
RN [85]
RP VARIANTS ASN-693; ASN-1040; ALA-1060 AND MET-1665.
RX PubMed=15026808; DOI=10.1038/sj.bjc.6601656;
RA Claes K., Poppe B., Coene I., De Paepe A., Messiaen L.;
RT "BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian
RT breast/ovarian cancer families.";
RL Br. J. Cancer 90:1244-1251(2004).
RN [86]
RP VARIANTS OVARIAN CANCER GLY-61; THR-1411; ARG-1697 AND TRP-1699.
RX PubMed=14746861; DOI=10.1016/j.ejca.2003.09.016;
RA Malander S., Ridderheim M., Masbaeck A., Loman N., Kristoffersson U.,
RA Olsson H., Nilbert M., Borg A.;
RT "One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2
RT mutations: results of a prospective study in Southern Sweden.";
RL Eur. J. Cancer 40:422-428(2004).
RN [87]
RP VARIANTS BC/BROVCA1 LYS-10; LYS-23; ILE-1187; HIS-1200 AND TYR-1217,
RP VARIANTS BC ILE-1204 AND ASN-1207, VARIANTS BROVCA1 LEU-1226 AND
RP GLY-1243, AND VARIANT ARG-1183.
RX PubMed=14722926; DOI=10.1002/humu.9213;
RA Valarmathi M.T., Sawhney M., Deo S.S.V., Shukla N.K., Das S.N.;
RT "Novel germline mutations in the BRCA1 and BRCA2 genes in Indian
RT breast and breast-ovarian cancer families.";
RL Hum. Mutat. 23:205-205(2004).
RN [88]
RP VARIANTS HIS-856; LEU-871; GLY-1038; ARG-1183; THR-1628; GLN-1690 AND
RP GLY-1713.
RX PubMed=15365993; DOI=10.1002/humu.9275;
RA Seo J.H., Cho D.-Y., Ahn S.-H., Yoon K.-S., Kang C.-S., Cho H.M.,
RA Lee H.S., Choe J.J., Choi C.W., Kim B.S., Shin S.W., Kim Y.H.,
RA Kim J.S., Son G.-S., Lee J.-B., Koo B.H.;
RT "BRCA1 and BRCA2 germline mutations in Korean patients with sporadic
RT breast cancer.";
RL Hum. Mutat. 24:350-350(2004).
RN [89]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-30; PHE-758 AND CYS-778.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [90]
RP VARIANTS THR-18; MET-1495; GLY-1623; ILE-1685; ALA-1685; ARG-1689;
RP TRP-1699; GLU-1706; GLU-1708; ARG-1715; ARG-1738; PRO-1764; SER-1766
RP AND VAL-1788.
RX PubMed=17924331; DOI=10.1086/521032;
RA Easton D.F., Deffenbaugh A.M., Pruss D., Frye C., Wenstrup R.J.,
RA Allen-Brady K., Tavtigian S.V., Monteiro A.N.A., Iversen E.S.,
RA Couch F.J., Goldgar D.E.;
RT "A systematic genetic assessment of 1,433 sequence variants of unknown
RT clinical significance in the BRCA1 and BRCA2 breast cancer-
RT predisposition genes.";
RL Am. J. Hum. Genet. 81:873-883(2007).
RN [91]
RP CHARACTERIZATION OF VARIANTS GLY-1623 AND ILE-1685.
RX PubMed=20513136; DOI=10.1002/humu.21267;
RA Walker L.C., Whiley P.J., Couch F.J., Farrugia D.J., Healey S.,
RA Eccles D.M., Lin F., Butler S.A., Goff S.A., Thompson B.A.,
RA Lakhani S.R., Da Silva L.M., Tavtigian S.V., Goldgar D.E., Brown M.A.,
RA Spurdle A.B.;
RT "Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence
RT variants encoding missense substitutions: implications for prediction
RT of pathogenicity.";
RL Hum. Mutat. 31:E1484-E1505(2010).
RN [92]
RP CHARACTERIZATION OF VARIANTS BC PHE-4; THR-18; GLN-45; GLY-61; GLY-64;
RP TYR-67; LYS-132; HIS-142; PHE-147; PRO-165; TRP-170; TYR-186; ILE-191;
RP MET-231; VAL-245; VAL-246; LEU-271; PHE-668; ASN-695; LEU-798;
RP TYR-810; LYS-826; GLN-841; HIS-856; ASN-1101; ASN-1140; GLY-1140;
RP LYS-1214; LYS-1236; SER-1267; VAL-1282; SER-1297 DEL; ARG-1301;
RP LYS-1346; ILE-1378; VAL-1400; PRO-1407; THR-1411; GLY-1443; GLY-1448;
RP CYS-1486; MET-1534; PRO-1589; THR-1628; PRO-1651; PHE-1651; PHE-1655;
RP ARG-1686; GLN-1686; VAL-1688 DEL; ILE-1691; TRP-1699; GLN-1699;
RP GLU-1706; ALA-1706; GLU-1708; CYS-1718; ALA-1720; LYS-1735; ALA-1736;
RP GLY-1739; VAL-1739; GLN-1746; THR-1753; PRO-1764; SER-1767; VAL-1770;
RP CYS-1782; THR-1789; ASP-1794; ASP-1804; ARG-1812; ARG-1837 AND
RP LEU-1862, AND VARIANTS CYS-105; CYS-866; ALA-1060; LYS-1250 AND
RP ILE-1652.
RX PubMed=23867111; DOI=10.1158/2159-8290.CD-13-0094;
RA Bouwman P., van der Gulden H., van der Heijden I., Drost R.,
RA Klijn C.N., Prasetyanti P., Pieterse M., Wientjens E., Seibler J.,
RA Hogervorst F.B., Jonkers J.;
RT "A high-throughput functional complementation assay for classification
RT of BRCA1 missense variants.";
RL Cancer Discov. 3:1142-1155(2013).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that specifically mediates
CC the formation of 'Lys-6'-linked polyubiquitin chains and plays a
CC central role in DNA repair by facilitating cellular responses to
CC DNA damage. It is unclear whether it also mediates the formation
CC of other types of polyubiquitin chains. The E3 ubiquitin-protein
CC ligase activity is required for its tumor suppressor function. The
CC BRCA1-BARD1 heterodimer coordinates a diverse range of cellular
CC pathways such as DNA damage repair, ubiquitination and
CC transcriptional regulation to maintain genomic stability.
CC Regulates centrosomal microtubule nucleation. Required for normal
CC cell cycle progression from G2 to mitosis. Required for
CC appropriate cell cycle arrests after ionizing irradiation in both
CC the S-phase and the G2 phase of the cell cycle. Involved in
CC transcriptional regulation of P21 in response to DNA damage.
CC Required for FANCD2 targeting to sites of DNA damage. May function
CC as a transcriptional regulator. Inhibits lipid synthesis by
CC binding to inactive phosphorylated ACACA and preventing its
CC dephosphorylation. Contributes to homologous recombination repair
CC (HRR) via its direct interaction with PALB2, fine-tunes
CC recombinational repair partly through its modulatory role in the
CC PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA
CC breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1
CC activation and controls cell cycle G2/M checkpoints on DNA damage
CC via BRCA1-mediated ubiquitination of RBBP8. Acts as a
CC transcriptional activator (PubMed:20160719).
CC {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175,
CC ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12887909,
CC ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165,
CC ECO:0000269|PubMed:14990569, ECO:0000269|PubMed:16326698,
CC ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340,
CC ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748,
CC ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:20364141}.
CC -!- ENZYME REGULATION: The E3 ubiquitin-protein ligase activity is
CC inhibited by phosphorylation by AURKA. Activity is increased by
CC phosphatase treatment. {ECO:0000269|PubMed:18056443}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Heterodimer with BARD1. Part of the BRCA1-associated
CC genome surveillance complex (BASC), which contains BRCA1, MSH2,
CC MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN)
CC complex. This association could be a dynamic process changing
CC throughout the cell cycle and within subnuclear domains. Component
CC of the BRCA1-A complex, at least composed of the BRCA1, BARD1,
CC UIMC1, BRCC3, BRE and BABAM1. Interacts (via the BRCT domains)
CC with FAM175A. Component of the BRCA1-RBBP8 complex. Interacts (via
CC the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the
CC interaction ubiquitinates RBBP8, regulates CHEK1 activation, and
CC involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA
CC damage. Associates with RNA polymerase II holoenzyme. Interacts
CC with SMC1A, COBRA1, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3,
CC AURKA, UBXN1 and KIAA0101/PAF15. Interacts (via BRCT domains) with
CC BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated
CC form). Interacts with H2AFX (phosphorylated on 'Ser-140').
CC Interacts (via the BRCT domains) with ACACA (phosphorylated form);
CC the interaction prevents dephosphorylation of ACACA. Part of a
CC BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly
CC with PALB2; the interaction is essential for its function in HRR.
CC Interacts directly with BRCA2; the interaction occurs only in the
CC presence of PALB2 which serves as the bridging protein. Interacts
CC (via the BRCT domains) with LMO4; the interaction represses the
CC transcriptional activity of BRCA1. Interacts (via the BRCT
CC domains) with CCAR2 (via N-terminus); the interaction represses
CC the transcriptional activator activity of BRCA1.
CC {ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:11301010,
CC ECO:0000269|PubMed:11573085, ECO:0000269|PubMed:11739404,
CC ECO:0000269|PubMed:11751867, ECO:0000269|PubMed:11836499,
CC ECO:0000269|PubMed:11877377, ECO:0000269|PubMed:12360400,
CC ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:12890688,
CC ECO:0000269|PubMed:14636569, ECO:0000269|PubMed:14976165,
CC ECO:0000269|PubMed:14990569, ECO:0000269|PubMed:15096610,
CC ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:15456891,
CC ECO:0000269|PubMed:16101277, ECO:0000269|PubMed:16326698,
CC ECO:0000269|PubMed:16698035, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121,
CC ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:18452305,
CC ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748,
CC ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:19369211,
CC ECO:0000269|PubMed:20159462, ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:21673012,
CC ECO:0000269|PubMed:9528852, ECO:0000269|PubMed:9811458}.
CC -!- INTERACTION:
CC Q13085:ACACA; NbExp=2; IntAct=EBI-349905, EBI-717681;
CC Q92560:BAP1; NbExp=3; IntAct=EBI-349905, EBI-1791447;
CC Q99728:BARD1; NbExp=9; IntAct=EBI-349905, EBI-473181;
CC P10415:BCL2; NbExp=6; IntAct=EBI-349905, EBI-77694;
CC Q7Z569:BRAP; NbExp=3; IntAct=EBI-349905, EBI-349900;
CC Q6PJG6:BRAT1; NbExp=6; IntAct=EBI-349905, EBI-10826195;
CC Q9BX63:BRIP1; NbExp=12; IntAct=EBI-349905, EBI-3509650;
CC P24385:CCND1; NbExp=3; IntAct=EBI-349905, EBI-375001;
CC P24864:CCNE1; NbExp=2; IntAct=EBI-349905, EBI-519526;
CC O14757:CHEK1; NbExp=3; IntAct=EBI-349905, EBI-974488;
CC P03372:ESR1; NbExp=12; IntAct=EBI-349905, EBI-78473;
CC Q61188:Ezh2 (xeno); NbExp=5; IntAct=EBI-349905, EBI-904311;
CC Q6UWZ7:FAM175A; NbExp=10; IntAct=EBI-349905, EBI-1263451;
CC Q14192:FHL2; NbExp=6; IntAct=EBI-349905, EBI-701903;
CC P78347:GTF2I; NbExp=5; IntAct=EBI-349905, EBI-359622;
CC P16104:H2AFX; NbExp=4; IntAct=EBI-349905, EBI-494830;
CC P10809:HSPD1; NbExp=2; IntAct=EBI-349905, EBI-352528;
CC Q16666:IFI16; NbExp=9; IntAct=EBI-349905, EBI-2867186;
CC P52292:KPNA2; NbExp=3; IntAct=EBI-349905, EBI-349938;
CC Q8WX92:NELFB; NbExp=5; IntAct=EBI-349905, EBI-347721;
CC P62136:PPP1CA; NbExp=2; IntAct=EBI-349905, EBI-357253;
CC P62140:PPP1CB; NbExp=3; IntAct=EBI-349905, EBI-352350;
CC P36873:PPP1CC; NbExp=2; IntAct=EBI-349905, EBI-356283;
CC Q99708:RBBP8; NbExp=9; IntAct=EBI-349905, EBI-745715;
CC Q9Y4A5:TRRAP; NbExp=8; IntAct=EBI-349905, EBI-399128;
CC Q96RL1:UIMC1; NbExp=9; IntAct=EBI-349905, EBI-725300;
CC Q6NZY4:ZCCHC8; NbExp=2; IntAct=EBI-349905, EBI-1263058;
CC Q9GZX5:ZNF350; NbExp=3; IntAct=EBI-349905, EBI-396421;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15133502,
CC ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:9528852}.
CC Chromosome {ECO:0000250|UniProtKB:P48754}. Cytoplasm
CC {ECO:0000269|PubMed:20160719}. Note=Localizes at sites of DNA
CC damage at double-strand breaks (DSBs); recruitment to DNA damage
CC sites is mediated by the BRCA1-A complex. Translocated to the
CC cytoplasm during UV-induced apoptosis.
CC {ECO:0000269|PubMed:20160719}.
CC -!- SUBCELLULAR LOCATION: Isoform 3: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: Isoform 5: Cytoplasm
CC {ECO:0000269|PubMed:8972225}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=8;
CC Name=1;
CC IsoId=P38398-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P38398-2; Sequence=VSP_047891;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay.;
CC Name=3; Synonyms=Delta11b;
CC IsoId=P38398-3; Sequence=VSP_035399, VSP_043797;
CC Name=4; Synonyms=DeltaBRCA1(17aa);
CC IsoId=P38398-4; Sequence=VSP_035396;
CC Note=Produced by alternative initiation at Met-18 of isoform 1.;
CC Name=5; Synonyms=Delta11, Delta772-3095;
CC IsoId=P38398-5; Sequence=VSP_035398;
CC Name=6;
CC IsoId=P38398-6; Sequence=VSP_035399, VSP_043797, VSP_043798;
CC Note=No experimental confirmation available.;
CC Name=7;
CC IsoId=P38398-7; Sequence=VSP_055404;
CC Note=No experimental confirmation available. Ref.8 (AAI15038)
CC sequence is in conflict in position: 1461:N->D. {ECO:0000305};
CC Name=8;
CC IsoId=P38398-8; Sequence=VSP_057569;
CC Note=No experimental confirmation available. The N-terminus is
CC confirmed by several cDNAs. {ECO:0000305};
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are widely expressed.
CC Isoform 3 is reduced or absent in several breast and ovarian
CC cancer cell lines.
CC -!- DOMAIN: The BRCT domains recognize and bind phosphorylated pSXXF
CC motif on proteins. The interaction with the phosphorylated pSXXF
CC motif of FAM175A/Abraxas, recruits BRCA1 at DNA damage sites.
CC {ECO:0000269|PubMed:20159462}.
CC -!- DOMAIN: The RING-type zinc finger domain interacts with BAP1.
CC {ECO:0000269|PubMed:20159462}.
CC -!- PTM: Phosphorylation at Ser-308 by AURKA is required for normal
CC cell cycle progression from G2 to mitosis. Phosphorylated in
CC response to IR, UV, and various stimuli that cause checkpoint
CC activation, probably by ATM or ATR. Phosphorylation at Ser-988 by
CC CHEK2 regulates mitotic spindle assembly.
CC {ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11114888,
CC ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:14990569,
CC ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:20364141,
CC ECO:0000269|PubMed:21144835}.
CC -!- PTM: Autoubiquitinated, undergoes 'Lys-6'-linked
CC polyubiquitination. 'Lys-6'-linked polyubiquitination does not
CC promote degradation. {ECO:0000269|PubMed:12890688,
CC ECO:0000269|PubMed:20351172}.
CC -!- POLYMORPHISM: There is evidence that the presence of the rare form
CC of Gln-356-Arg and Leu-871-Pro polymorphisms may be associated
CC with an increased risk for developing ovarian cancer.
CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy
CC originating from breast epithelial tissue. Breast neoplasms can be
CC distinguished by their histologic pattern. Invasive ductal
CC carcinoma is by far the most common type. Breast cancer is
CC etiologically and genetically heterogeneous. Important genetic
CC factors have been indicated by familial occurrence and bilateral
CC involvement. Mutations at more than one locus can be involved in
CC different families or even in the same case.
CC {ECO:0000269|PubMed:10323242, ECO:0000269|PubMed:12442275,
CC ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926,
CC ECO:0000269|PubMed:18285836, ECO:0000269|PubMed:7545954,
CC ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:7894493,
CC ECO:0000269|PubMed:7939630, ECO:0000269|PubMed:8554067,
CC ECO:0000269|PubMed:8723683, ECO:0000269|PubMed:8776600,
CC ECO:0000269|PubMed:9482581, ECO:0000269|PubMed:9609997,
CC ECO:0000269|PubMed:9760198}. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry. Mutations in BRCA1 are thought to be responsible for 45% of
CC inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold
CC increased risk of colon cancer, whereas male carriers face a 3-
CC fold increased risk of prostate cancer. Cells lacking BRCA1 show
CC defects in DNA repair by homologous recombination.
CC -!- DISEASE: Breast-ovarian cancer, familial, 1 (BROVCA1)
CC [MIM:604370]: A condition associated with familial predisposition
CC to cancer of the breast and ovaries. Characteristic features in
CC affected families are an early age of onset of breast cancer
CC (often before age 50), increased chance of bilateral cancers
CC (cancer that develop in both breasts, or both ovaries,
CC independently), frequent occurrence of breast cancer among men,
CC increased incidence of tumors of other specific organs, such as
CC the prostate. {ECO:0000269|PubMed:12938098,
CC ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:8968716}.
CC Note=Disease susceptibility is associated with variations
CC affecting the gene represented in this entry. Mutations in BRCA1
CC are thought to be responsible for more than 80% of inherited
CC breast-ovarian cancer.
CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer
CC defines malignancies originating from ovarian tissue. Although
CC many histologic types of ovarian tumors have been described,
CC epithelial ovarian carcinoma is the most common form. Ovarian
CC cancers are often asymptomatic and the recognized signs and
CC symptoms, even of late-stage disease, are vague. Consequently,
CC most patients are diagnosed with advanced disease.
CC {ECO:0000269|PubMed:10196379, ECO:0000269|PubMed:10486320,
CC ECO:0000269|PubMed:14746861}. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- DISEASE: Pancreatic cancer 4 (PNCA4) [MIM:614320]: A malignant
CC neoplasm of the pancreas. Tumors can arise from both the exocrine
CC and endocrine portions of the pancreas, but 95% of them develop
CC from the exocrine portion, including the ductal epithelium, acinar
CC cells, connective tissue, and lymphatic tissue.
CC {ECO:0000269|PubMed:18762988}. Note=Disease susceptibility is
CC associated with variations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Contains 2 BRCT domains. {ECO:0000255|PROSITE-
CC ProRule:PRU00033}.
CC -!- SIMILARITY: Contains 1 RING-type zinc finger.
CC {ECO:0000255|PROSITE-ProRule:PRU00175}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61673.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=AAI15038.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC Sequence=AAI15038.1; Type=Erroneous termination; Positions=526; Note=Translated as Gln.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BRCA1ID163ch17q21.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/brca1/";
CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC polymorphism database;
CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=BRCA1";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=BRCA1 entry;
CC URL="https://en.wikipedia.org/wiki/BRCA1";
CC -----------------------------------------------------------------------
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DR EMBL; U14680; AAA73985.1; -; mRNA.
DR EMBL; L78833; AAC37594.1; -; Genomic_DNA.
DR EMBL; U64805; AAC00049.1; -; mRNA.
DR EMBL; AF005068; AAB61673.1; ALT_SEQ; mRNA.
DR EMBL; DQ190450; ABA29208.1; -; Genomic_DNA.
DR EMBL; DQ190451; ABA29211.1; -; Genomic_DNA.
DR EMBL; DQ190452; ABA29214.1; -; Genomic_DNA.
DR EMBL; DQ190453; ABA29217.1; -; Genomic_DNA.
DR EMBL; DQ190454; ABA29220.1; -; Genomic_DNA.
DR EMBL; DQ190455; ABA29223.1; -; Genomic_DNA.
DR EMBL; DQ190456; ABA29226.1; -; Genomic_DNA.
DR EMBL; AY273801; AAP12647.1; -; Genomic_DNA.
DR EMBL; AC060780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC135721; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC072418; AAH72418.1; -; mRNA.
DR EMBL; BC115037; AAI15038.1; ALT_SEQ; mRNA.
DR CCDS; CCDS11453.1; -. [P38398-1]
DR CCDS; CCDS11454.2; -. [P38398-3]
DR CCDS; CCDS11455.2; -. [P38398-6]
DR CCDS; CCDS11456.2; -. [P38398-7]
DR CCDS; CCDS11459.2; -. [P38398-8]
DR PIR; A58881; A58881.
DR RefSeq; NP_009225.1; NM_007294.3. [P38398-1]
DR RefSeq; NP_009228.2; NM_007297.3. [P38398-8]
DR RefSeq; NP_009229.2; NM_007298.3. [P38398-3]
DR RefSeq; NP_009230.2; NM_007299.3. [P38398-6]
DR RefSeq; NP_009231.2; NM_007300.3. [P38398-7]
DR UniGene; Hs.194143; -.
DR PDB; 1JM7; NMR; -; A=1-110.
DR PDB; 1JNX; X-ray; 2.50 A; X=1646-1859.
DR PDB; 1N5O; X-ray; 2.80 A; X=1646-1859.
DR PDB; 1OQA; NMR; -; A=1755-1863.
DR PDB; 1T15; X-ray; 1.85 A; A=1646-1859.
DR PDB; 1T29; X-ray; 2.30 A; A=1646-1859.
DR PDB; 1T2U; X-ray; 2.80 A; A=1646-1859.
DR PDB; 1T2V; X-ray; 3.30 A; A/B/C/D/E=1646-1859.
DR PDB; 1Y98; X-ray; 2.50 A; A=1646-1859.
DR PDB; 2ING; X-ray; 3.60 A; X=1649-1859.
DR PDB; 3COJ; X-ray; 3.21 A; A/B/C/D/E/F/G/X=1646-1859.
DR PDB; 3K0H; X-ray; 2.70 A; A=1646-1859.
DR PDB; 3K0K; X-ray; 2.70 A; A=1646-1859.
DR PDB; 3K15; X-ray; 2.80 A; A=1646-1859.
DR PDB; 3K16; X-ray; 3.00 A; A=1646-1859.
DR PDB; 3PXA; X-ray; 2.55 A; A=1646-1859.
DR PDB; 3PXB; X-ray; 2.50 A; A=1646-1859.
DR PDB; 3PXC; X-ray; 2.80 A; X=1646-1859.
DR PDB; 3PXD; X-ray; 2.80 A; A=1646-1859.
DR PDB; 3PXE; X-ray; 2.85 A; A/B/C/D=1646-1859.
DR PDB; 4IFI; X-ray; 2.20 A; A=1646-1859.
DR PDB; 4IGK; X-ray; 1.75 A; A/B=1646-1859.
DR PDB; 4JLU; X-ray; 3.50 A; A=1649-1859.
DR PDB; 4OFB; X-ray; 3.05 A; A=1646-1859.
DR PDB; 4U4A; X-ray; 3.51 A; A/B/C=1646-1859.
DR PDBsum; 1JM7; -.
DR PDBsum; 1JNX; -.
DR PDBsum; 1N5O; -.
DR PDBsum; 1OQA; -.
DR PDBsum; 1T15; -.
DR PDBsum; 1T29; -.
DR PDBsum; 1T2U; -.
DR PDBsum; 1T2V; -.
DR PDBsum; 1Y98; -.
DR PDBsum; 2ING; -.
DR PDBsum; 3COJ; -.
DR PDBsum; 3K0H; -.
DR PDBsum; 3K0K; -.
DR PDBsum; 3K15; -.
DR PDBsum; 3K16; -.
DR PDBsum; 3PXA; -.
DR PDBsum; 3PXB; -.
DR PDBsum; 3PXC; -.
DR PDBsum; 3PXD; -.
DR PDBsum; 3PXE; -.
DR PDBsum; 4IFI; -.
DR PDBsum; 4IGK; -.
DR PDBsum; 4JLU; -.
DR PDBsum; 4OFB; -.
DR PDBsum; 4U4A; -.
DR DisProt; DP00238; -.
DR ProteinModelPortal; P38398; -.
DR SMR; P38398; 1-103, 1649-1859.
DR BioGrid; 107140; 561.
DR DIP; DIP-5971N; -.
DR IntAct; P38398; 74.
DR MINT; MINT-90433; -.
DR STRING; 9606.ENSP00000418960; -.
DR BindingDB; P38398; -.
DR ChEMBL; CHEMBL5990; -.
DR PhosphoSite; P38398; -.
DR BioMuta; BRCA1; -.
DR DMDM; 728984; -.
DR MaxQB; P38398; -.
DR PaxDb; P38398; -.
DR PRIDE; P38398; -.
DR DNASU; 672; -.
DR Ensembl; ENST00000352993; ENSP00000312236; ENSG00000012048. [P38398-5]
DR Ensembl; ENST00000357654; ENSP00000350283; ENSG00000012048. [P38398-1]
DR Ensembl; ENST00000461221; ENSP00000418548; ENSG00000012048. [P38398-2]
DR Ensembl; ENST00000461798; ENSP00000417988; ENSG00000012048. [P38398-2]
DR Ensembl; ENST00000468300; ENSP00000417148; ENSG00000012048. [P38398-6]
DR Ensembl; ENST00000471181; ENSP00000418960; ENSG00000012048. [P38398-7]
DR Ensembl; ENST00000491747; ENSP00000420705; ENSG00000012048. [P38398-3]
DR Ensembl; ENST00000493795; ENSP00000418775; ENSG00000012048. [P38398-8]
DR GeneID; 672; -.
DR KEGG; hsa:672; -.
DR UCSC; uc002icp.4; human. [P38398-2]
DR UCSC; uc002icq.3; human. [P38398-1]
DR UCSC; uc002icu.3; human. [P38398-6]
DR UCSC; uc010whq.1; human. [P38398-3]
DR CTD; 672; -.
DR GeneCards; BRCA1; -.
DR GeneReviews; BRCA1; -.
DR HGNC; HGNC:1100; BRCA1.
DR HPA; CAB001946; -.
DR HPA; CAB018369; -.
DR HPA; HPA034966; -.
DR MIM; 113705; gene.
DR MIM; 114480; phenotype.
DR MIM; 167000; phenotype.
DR MIM; 604370; phenotype.
DR MIM; 614320; phenotype.
DR neXtProt; NX_P38398; -.
DR Orphanet; 1333; Familial pancreatic carcinoma.
DR Orphanet; 1331; Familial prostate cancer.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR Orphanet; 227535; Hereditary breast cancer.
DR Orphanet; 213524; Hereditary site-specific ovarian cancer syndrome.
DR Orphanet; 168829; Primary peritoneal carcinoma.
DR PharmGKB; PA25411; -.
DR eggNOG; ENOG410ITQ4; Eukaryota.
DR eggNOG; ENOG4112BIH; LUCA.
DR GeneTree; ENSGT00440000034289; -.
DR HOGENOM; HOG000230969; -.
DR HOVERGEN; HBG050730; -.
DR InParanoid; P38398; -.
DR KO; K10605; -.
DR OMA; FQHLLFG; -.
DR OrthoDB; EOG79CXXK; -.
DR PhylomeDB; P38398; -.
DR BRENDA; 6.3.2.19; 2681.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-419524; Fanconi Anemia pathway.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-75148; ATM mediated phosphorylation of repair proteins.
DR Reactome; R-HSA-75154; Recruitment of repair and signaling proteins to double-strand breaks.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR SignaLink; P38398; -.
DR UniPathway; UPA00143; -.
DR ChiTaRS; BRCA1; human.
DR EvolutionaryTrace; P38398; -.
DR GeneWiki; BRCA1; -.
DR GenomeRNAi; 672; -.
DR NextBio; 2752; -.
DR PMAP-CutDB; P38398; -.
DR PRO; PR:P38398; -.
DR Proteomes; UP000005640; Chromosome 17.
DR Bgee; P38398; -.
DR CleanEx; HS_BRCA1; -.
DR ExpressionAtlas; P38398; baseline and differential.
DR Genevisible; P38398; HS.
DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0008274; C:gamma-tubulin ring complex; NAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; NAS:UniProtKB.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
DR GO; GO:0015631; F:tubulin binding; NAS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; TAS:ProtInc.
DR GO; GO:0071681; P:cellular response to indole-3-methanol; IDA:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL.
DR GO; GO:0007098; P:centrosome cycle; IEA:Ensembl.
DR GO; GO:0043009; P:chordate embryonic development; IBA:GO_Central.
DR GO; GO:0031052; P:chromosome breakage; IEA:Ensembl.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; TAS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:Reactome.
DR GO; GO:0006260; P:DNA replication; IEA:Ensembl.
DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IBA:GO_Central.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:HGNC.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:MGI.
DR GO; GO:0046600; P:negative regulation of centriole replication; NAS:UniProtKB.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0035067; P:negative regulation of histone acetylation; IBA:GO_Central.
DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; IEA:Ensembl.
DR GO; GO:0051573; P:negative regulation of histone H3-K9 methylation; IDA:BHF-UCL.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IMP:CACAO.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0071158; P:positive regulation of cell cycle arrest; IDA:BHF-UCL.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IDA:BHF-UCL.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IDA:BHF-UCL.
DR GO; GO:2000617; P:positive regulation of histone H3-K9 acetylation; IDA:BHF-UCL.
DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; IEA:Ensembl.
DR GO; GO:2000620; P:positive regulation of histone H4-K16 acetylation; IDA:BHF-UCL.
DR GO; GO:0070512; P:positive regulation of histone H4-K20 methylation; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:BHF-UCL.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0006301; P:postreplication repair; IDA:HGNC.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome.
DR GO; GO:0016567; P:protein ubiquitination; IDA:HGNC.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB.
DR GO; GO:0044030; P:regulation of DNA methylation; IEA:Ensembl.
DR GO; GO:0006349; P:regulation of gene expression by genetic imprinting; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006359; P:regulation of transcription from RNA polymerase III promoter; TAS:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR011364; BRCA1.
DR InterPro; IPR031099; BRCA1-associated.
DR InterPro; IPR025994; BRCA1_serine_dom.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13763; PTHR13763; 1.
DR PANTHER; PTHR13763:SF0; PTHR13763:SF0; 1.
DR Pfam; PF00533; BRCT; 2.
DR Pfam; PF12820; BRCT_assoc; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR PIRSF; PIRSF001734; BRCA1; 1.
DR PRINTS; PR00493; BRSTCANCERI.
DR SMART; SM00292; BRCT; 2.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative initiation;
KW Alternative splicing; Cell cycle; Chromosome; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Disease mutation; DNA damage;
KW DNA recombination; DNA repair; DNA-binding; Fatty acid biosynthesis;
KW Fatty acid metabolism; Isopeptide bond; Ligase; Lipid biosynthesis;
KW Lipid metabolism; Metal-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1 1863 Breast cancer type 1 susceptibility
FT protein.
FT /FTId=PRO_0000055830.
FT DOMAIN 1642 1736 BRCT 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00033}.
FT DOMAIN 1756 1855 BRCT 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00033}.
FT ZN_FING 24 65 RING-type. {ECO:0000255|PROSITE-
FT ProRule:PRU00175}.
FT REGION 1397 1424 Interaction with PALB2.
FT COMPBIAS 651 654 Poly-Lys.
FT MOD_RES 1 1 N-acetylmethionine.
FT {ECO:0000244|PubMed:22814378}.
FT MOD_RES 114 114 Phosphoserine.
FT {ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692}.
FT MOD_RES 308 308 Phosphoserine; by AURKA.
FT {ECO:0000269|PubMed:14990569}.
FT MOD_RES 395 395 Phosphoserine.
FT {ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:19690332}.
FT MOD_RES 398 398 Phosphoserine.
FT {ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:19690332}.
FT MOD_RES 423 423 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 694 694 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 725 725 Phosphoserine.
FT {ECO:0000250|UniProtKB:P48754}.
FT MOD_RES 753 753 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT MOD_RES 840 840 Phosphoserine.
FT {ECO:0000250|UniProtKB:P48754}.
FT MOD_RES 988 988 Phosphoserine; by CHEK2.
FT {ECO:0000269|PubMed:10724175,
FT ECO:0000269|PubMed:20364141}.
FT MOD_RES 1143 1143 Phosphoserine; by ATR; in vitro.
FT {ECO:0000269|PubMed:11114888}.
FT MOD_RES 1211 1211 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT MOD_RES 1217 1217 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT MOD_RES 1218 1218 Phosphoserine.
FT {ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:21406692}.
FT MOD_RES 1280 1280 Phosphoserine; by ATR; in vitro.
FT {ECO:0000269|PubMed:11114888}.
FT MOD_RES 1328 1328 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 1336 1336 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692}.
FT MOD_RES 1342 1342 Phosphoserine.
FT {ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692}.
FT MOD_RES 1387 1387 Phosphoserine; by ATM and ATR.
FT {ECO:0000269|PubMed:11114888}.
FT MOD_RES 1394 1394 Phosphothreonine; by ATR; in vitro.
FT {ECO:0000269|PubMed:11114888}.
FT MOD_RES 1423 1423 Phosphoserine; by ATM and ATR.
FT {ECO:0000269|PubMed:11114888}.
FT MOD_RES 1457 1457 Phosphoserine; by ATR; in vitro.
FT {ECO:0000269|PubMed:11114888}.
FT MOD_RES 1524 1524 Phosphoserine; by ATM.
FT {ECO:0000269|PubMed:21144835}.
FT CROSSLNK 339 339 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 459 459 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 583 583 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 654 654 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 734 734 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 739 739 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT VAR_SEQ 1 47 Missing (in isoform 8).
FT /FTId=VSP_057569.
FT VAR_SEQ 1 17 Missing (in isoform 4). {ECO:0000305}.
FT /FTId=VSP_035396.
FT VAR_SEQ 64 1863 Missing (in isoform 2).
FT {ECO:0000303|Ref.4}.
FT /FTId=VSP_047891.
FT VAR_SEQ 224 1365 Missing (in isoform 5). {ECO:0000305}.
FT /FTId=VSP_035398.
FT VAR_SEQ 264 1366 Missing (in isoform 3 and isoform 6).
FT {ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9010228}.
FT /FTId=VSP_035399.
FT VAR_SEQ 1453 1453 Missing (in isoform 3 and isoform 6).
FT {ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9010228}.
FT /FTId=VSP_043797.
FT VAR_SEQ 1453 1453 A -> DSHIHGQRNNSMFSKRPREHIS (in isoform
FT 7). {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_055404.
FT VAR_SEQ 1778 1863 DQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTED
FT NGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQIP
FT HSHY -> GCPPNCGCAARCLDRGQWLPCNWADV (in
FT isoform 6).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_043798.
FT VARIANT 4 4 S -> F (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070458.
FT VARIANT 10 10 E -> K (in BC and BROVCA1).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020679.
FT VARIANT 11 11 V -> A (found in breast-ovarian cancer
FT patients; unknown pathological
FT significance; dbSNP:rs80357017).
FT /FTId=VAR_007754.
FT VARIANT 18 18 M -> T (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_063899.
FT VARIANT 21 21 I -> V (found in breast-ovarian cancer
FT patients; unknown pathological
FT significance; dbSNP:rs80357406).
FT /FTId=VAR_007755.
FT VARIANT 22 22 L -> S (in BC).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007756.
FT VARIANT 23 23 E -> K (in BC and BROVCA1).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020680.
FT VARIANT 30 30 L -> F (in a breast cancer sample;
FT somatic mutation).
FT {ECO:0000269|PubMed:16959974}.
FT /FTId=VAR_035947.
FT VARIANT 45 45 K -> Q (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070459.
FT VARIANT 61 61 C -> G (in BC and ovarian cancer; no
FT interaction with BAP1; dbSNP:rs28897672).
FT {ECO:0000269|PubMed:12938098,
FT ECO:0000269|PubMed:14746861,
FT ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:7894493,
FT ECO:0000269|PubMed:8554067,
FT ECO:0000269|PubMed:9528852,
FT ECO:0000269|PubMed:9760198}.
FT /FTId=VAR_007757.
FT VARIANT 64 64 C -> G (in BC; no interaction with BAP1).
FT {ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:7894491,
FT ECO:0000269|PubMed:9482581,
FT ECO:0000269|PubMed:9528852}.
FT /FTId=VAR_007758.
FT VARIANT 64 64 C -> Y (in dbSNP:rs55851803).
FT /FTId=VAR_007759.
FT VARIANT 67 67 D -> Y (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070460.
FT VARIANT 71 71 R -> K (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020681.
FT VARIANT 105 105 Y -> C. {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070461.
FT VARIANT 132 132 N -> K (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070462.
FT VARIANT 142 142 P -> H (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070463.
FT VARIANT 147 147 L -> F (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070464.
FT VARIANT 153 153 S -> R (in dbSNP:rs28897674).
FT /FTId=VAR_052077.
FT VARIANT 165 165 L -> P (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070465.
FT VARIANT 170 170 R -> W (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070466.
FT VARIANT 186 186 S -> Y (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070467.
FT VARIANT 191 191 V -> I (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070468.
FT VARIANT 227 227 E -> K (in ovarian cancer; unknown
FT pathological significance).
FT /FTId=VAR_008759.
FT VARIANT 231 231 T -> M (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070469.
FT VARIANT 239 239 H -> R. {ECO:0000269|PubMed:9010228,
FT ECO:0000269|PubMed:9760198}.
FT /FTId=VAR_007760.
FT VARIANT 245 245 D -> V (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070470.
FT VARIANT 246 246 L -> V (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070471.
FT VARIANT 271 271 V -> L (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070472.
FT VARIANT 271 271 V -> M (in BC; dbSNP:rs80357244).
FT {ECO:0000269|PubMed:8723683}.
FT /FTId=VAR_007761.
FT VARIANT 275 275 G -> S (in dbSNP:rs8176153).
FT {ECO:0000269|Ref.6}.
FT /FTId=VAR_019944.
FT VARIANT 346 346 P -> S (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:10323242}.
FT /FTId=VAR_008760.
FT VARIANT 356 356 Q -> R (common polymorphism;
FT dbSNP:rs1799950).
FT {ECO:0000269|PubMed:7894493,
FT ECO:0000269|Ref.5, ECO:0000269|Ref.6}.
FT /FTId=VAR_007762.
FT VARIANT 369 369 Missing (in BC).
FT /FTId=VAR_007763.
FT VARIANT 379 379 I -> M (in dbSNP:rs56128296).
FT /FTId=VAR_007764.
FT VARIANT 461 461 F -> L (in BC; dbSNP:rs56046357).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007765.
FT VARIANT 465 465 Y -> D (in BC).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007766.
FT VARIANT 507 507 R -> I (found in breast-ovarian cancer
FT patients; unknown pathological
FT significance; dbSNP:rs80357224).
FT /FTId=VAR_007767.
FT VARIANT 552 552 G -> V (in BC).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007768.
FT VARIANT 656 656 N -> I. {ECO:0000269|PubMed:12442274}.
FT /FTId=VAR_020682.
FT VARIANT 668 668 L -> F (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070473.
FT VARIANT 693 693 D -> N (rare polymorphism;
FT dbSNP:rs4986850).
FT {ECO:0000269|PubMed:15026808,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_007769.
FT VARIANT 695 695 D -> N (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070474.
FT VARIANT 723 723 N -> D (in dbSNP:rs4986845).
FT /FTId=VAR_020110.
FT VARIANT 749 749 D -> Y (in BC).
FT {ECO:0000269|PubMed:12442275}.
FT /FTId=VAR_020683.
FT VARIANT 758 758 L -> F (in a breast cancer sample;
FT somatic mutation).
FT {ECO:0000269|PubMed:16959974}.
FT /FTId=VAR_035948.
FT VARIANT 772 772 V -> A (rare polymorphism).
FT {ECO:0000269|PubMed:7894491,
FT ECO:0000269|PubMed:9482581}.
FT /FTId=VAR_007770.
FT VARIANT 778 778 G -> C (in a breast cancer sample;
FT somatic mutation).
FT {ECO:0000269|PubMed:16959974}.
FT /FTId=VAR_035949.
FT VARIANT 798 798 P -> L (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070475.
FT VARIANT 810 810 N -> Y (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070476.
FT VARIANT 820 820 K -> E (rare polymorphism;
FT dbSNP:rs56082113).
FT {ECO:0000269|PubMed:9482581}.
FT /FTId=VAR_007771.
FT VARIANT 826 826 T -> K (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro; dbSNP:rs28897683).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_007772.
FT VARIANT 835 835 H -> Y (in BROVCA1; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020684.
FT VARIANT 841 841 R -> Q (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070477.
FT VARIANT 841 841 R -> W (in BROVCA1; unknown pathological
FT significance; dbSNP:rs1800709).
FT {ECO:0000269|PubMed:8968716,
FT ECO:0000269|PubMed:9760198}.
FT /FTId=VAR_007773.
FT VARIANT 856 856 Y -> H (in a patient with sporadic breast
FT cancer; unknown pathological
FT significance; dbSNP:rs80356892).
FT {ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_020685.
FT VARIANT 866 866 R -> C. {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070478.
FT VARIANT 866 866 R -> Q (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020686.
FT VARIANT 871 871 P -> L (common polymorphism;
FT dbSNP:rs799917).
FT {ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:12442274,
FT ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_007774.
FT VARIANT 888 888 H -> Y (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020687.
FT VARIANT 892 892 L -> S (in BC).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007775.
FT VARIANT 925 925 I -> L (in dbSNP:rs4986847).
FT /FTId=VAR_021913.
FT VARIANT 960 960 G -> D (in BC).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007776.
FT VARIANT 989 989 F -> S (in dbSNP:rs4986848).
FT /FTId=VAR_020111.
FT VARIANT 1008 1008 M -> I (common polymorphism;
FT dbSNP:rs1800704).
FT /FTId=VAR_007777.
FT VARIANT 1025 1025 T -> I (in BC).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007778.
FT VARIANT 1038 1038 E -> G (common polymorphism;
FT dbSNP:rs16941).
FT {ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7894493,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_007779.
FT VARIANT 1040 1040 S -> N (rare polymorphism;
FT dbSNP:rs4986852).
FT {ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:7894491,
FT ECO:0000269|PubMed:7894493,
FT ECO:0000269|PubMed:9482581,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_007780.
FT VARIANT 1047 1047 V -> A (in BC).
FT {ECO:0000269|PubMed:9609997}.
FT /FTId=VAR_007781.
FT VARIANT 1060 1060 E -> A. {ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_020688.
FT VARIANT 1101 1101 S -> N (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070479.
FT VARIANT 1139 1139 S -> I (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020689.
FT VARIANT 1140 1140 S -> G (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro; dbSNP:rs2227945).
FT {ECO:0000269|PubMed:23867111,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_019945.
FT VARIANT 1140 1140 S -> N (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070480.
FT VARIANT 1150 1150 P -> S (in BC; dbSNP:rs80357272).
FT {ECO:0000269|PubMed:8723683}.
FT /FTId=VAR_007782.
FT VARIANT 1183 1183 K -> R (common polymorphism;
FT dbSNP:rs16942).
FT {ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:14722926,
FT ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7894493,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_007783.
FT VARIANT 1187 1187 S -> I (in BC and BROVCA1).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020690.
FT VARIANT 1200 1200 Q -> H (in BC and BROVCA1;
FT dbSNP:rs56214134).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020691.
FT VARIANT 1204 1204 R -> I (in BC).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020692.
FT VARIANT 1207 1207 K -> N (in BC).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020693.
FT VARIANT 1210 1210 E -> G (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020694.
FT VARIANT 1214 1214 E -> K (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070481.
FT VARIANT 1217 1217 S -> Y (in BC and BROVCA1).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020695.
FT VARIANT 1219 1219 E -> D (found in breast-ovarian cancer
FT patients; unknown pathological
FT significance; dbSNP:rs80356876).
FT /FTId=VAR_007784.
FT VARIANT 1226 1226 F -> L (in BROVCA1).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020696.
FT VARIANT 1236 1236 N -> K (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro; dbSNP:rs28897687).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_052078.
FT VARIANT 1243 1243 R -> G (in BROVCA1).
FT {ECO:0000269|PubMed:14722926}.
FT /FTId=VAR_020697.
FT VARIANT 1250 1250 E -> K (in dbSNP:rs28897686).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_052079.
FT VARIANT 1267 1267 L -> S (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070482.
FT VARIANT 1282 1282 E -> V (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070483.
FT VARIANT 1297 1297 S -> P (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020698.
FT VARIANT 1297 1297 Missing (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070484.
FT VARIANT 1301 1301 S -> R (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070485.
FT VARIANT 1346 1346 E -> K (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070486.
FT VARIANT 1347 1347 R -> G (in dbSNP:rs28897689).
FT {ECO:0000269|PubMed:12215251}.
FT /FTId=VAR_007785.
FT VARIANT 1378 1378 V -> I (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070487.
FT VARIANT 1400 1400 M -> V (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070488.
FT VARIANT 1406 1406 K -> N (polymorphism; dbSNP:rs1800707).
FT /FTId=VAR_008761.
FT VARIANT 1407 1407 L -> P (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070489.
FT VARIANT 1411 1411 M -> T (in BC and ovarian cancer; unknown
FT pathological significance; decreased
FT interaction with PALB2).
FT {ECO:0000269|PubMed:14746861,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_020699.
FT VARIANT 1431 1431 S -> P.
FT /FTId=VAR_007786.
FT VARIANT 1443 1443 R -> G (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:7894491,
FT ECO:0000269|PubMed:9482581}.
FT /FTId=VAR_007787.
FT VARIANT 1443 1443 R -> Q (in dbSNP:rs4986849).
FT /FTId=VAR_020112.
FT VARIANT 1448 1448 S -> G (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070490.
FT VARIANT 1486 1486 S -> C (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070491.
FT VARIANT 1495 1495 R -> M (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331}.
FT /FTId=VAR_063900.
FT VARIANT 1512 1512 S -> I (in dbSNP:rs1800744).
FT {ECO:0000269|PubMed:12215251,
FT ECO:0000269|PubMed:9482581,
FT ECO:0000269|PubMed:9760198}.
FT /FTId=VAR_007788.
FT VARIANT 1534 1534 V -> M (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070492.
FT VARIANT 1561 1561 T -> I (found in breast cancer; unknown
FT pathological significance;
FT dbSNP:rs56158747).
FT /FTId=VAR_007789.
FT VARIANT 1589 1589 R -> P (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070493.
FT VARIANT 1606 1606 K -> E (found in breast cancer; unknown
FT pathological significance).
FT /FTId=VAR_007790.
FT VARIANT 1613 1613 S -> G (common polymorphism;
FT dbSNP:rs1799966).
FT {ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:12442274,
FT ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7894493,
FT ECO:0000269|PubMed:9010228,
FT ECO:0000269|Ref.6}.
FT /FTId=VAR_007791.
FT VARIANT 1620 1620 T -> A (in dbSNP:rs8176219).
FT {ECO:0000269|Ref.6}.
FT /FTId=VAR_019946.
FT VARIANT 1623 1623 A -> G (could be associated with cancer
FT susceptibility; major splicing aberration
FT identified with this mutant).
FT {ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:20513136}.
FT /FTId=VAR_063901.
FT VARIANT 1628 1628 M -> T (in some patients with sporadic
FT breast cancer; unknown pathological
FT significance; dbSNP:rs4986854).
FT {ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_007793.
FT VARIANT 1628 1628 M -> V (found in breast and ovarian
FT cancer patients; unknown pathological
FT significance; dbSNP:rs80357465).
FT /FTId=VAR_007792.
FT VARIANT 1637 1637 P -> L (rare polymorphism).
FT {ECO:0000269|PubMed:7939630,
FT ECO:0000269|PubMed:9482581}.
FT /FTId=VAR_007794.
FT VARIANT 1641 1641 A -> P (in ovarian cancer; unknown
FT pathological significance;
FT dbSNP:rs1800726).
FT /FTId=VAR_008762.
FT VARIANT 1651 1651 S -> F (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070494.
FT VARIANT 1651 1651 S -> P (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070495.
FT VARIANT 1652 1652 M -> I (rare polymorphism;
FT dbSNP:rs1799967).
FT {ECO:0000269|PubMed:12215251,
FT ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:9482581}.
FT /FTId=VAR_007795.
FT VARIANT 1655 1655 S -> F (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070496.
FT VARIANT 1662 1662 F -> C (in dbSNP:rs28897695).
FT /FTId=VAR_052080.
FT VARIANT 1665 1665 V -> M. {ECO:0000269|PubMed:15026808}.
FT /FTId=VAR_020700.
FT VARIANT 1685 1685 T -> A (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331}.
FT /FTId=VAR_063902.
FT VARIANT 1685 1685 T -> I (could be associated with cancer
FT susceptibility; multifactorial likelihood
FT analysis provides evidence for
FT pathogenicity).
FT {ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:20513136}.
FT /FTId=VAR_063903.
FT VARIANT 1686 1686 H -> Q (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070497.
FT VARIANT 1686 1686 H -> R (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070498.
FT VARIANT 1688 1688 Missing (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070499.
FT VARIANT 1689 1689 M -> R (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331}.
FT /FTId=VAR_063904.
FT VARIANT 1690 1690 K -> Q (in some patients with sporadic
FT breast cancer; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:15365993}.
FT /FTId=VAR_020701.
FT VARIANT 1691 1691 T -> I (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070500.
FT VARIANT 1692 1692 D -> N (in ovarian cancer; unknown
FT pathological significance).
FT /FTId=VAR_008763.
FT VARIANT 1697 1697 C -> R (in ovarian cancer).
FT {ECO:0000269|PubMed:14746861}.
FT /FTId=VAR_020702.
FT VARIANT 1699 1699 R -> Q (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070501.
FT VARIANT 1699 1699 R -> W (in BC and ovarian cancer;
FT functionally impaired in vitro).
FT {ECO:0000269|PubMed:14746861,
FT ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_020703.
FT VARIANT 1706 1706 G -> A (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070502.
FT VARIANT 1706 1706 G -> E (in BC; unknown pathological
FT significance; dbSNP:rs80356860).
FT {ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_063905.
FT VARIANT 1708 1708 A -> E (in BC; abolishes ACACA binding;
FT dbSNP:rs28897696).
FT {ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:7939630}.
FT /FTId=VAR_007796.
FT VARIANT 1713 1713 V -> G. {ECO:0000269|PubMed:15365993}.
FT /FTId=VAR_007797.
FT VARIANT 1715 1715 S -> R (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331}.
FT /FTId=VAR_063906.
FT VARIANT 1718 1718 W -> C (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070503.
FT VARIANT 1720 1720 T -> A (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro; no effect on in vitro
FT phosphorylation by ATR).
FT {ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070504.
FT VARIANT 1735 1735 E -> K (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070505.
FT VARIANT 1736 1736 V -> A (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070506.
FT VARIANT 1738 1738 G -> R (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331}.
FT /FTId=VAR_063907.
FT VARIANT 1739 1739 D -> G (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070507.
FT VARIANT 1739 1739 D -> V (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070508.
FT VARIANT 1746 1746 H -> Q (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070509.
FT VARIANT 1749 1749 P -> R (in ovarian cancer; unknown
FT pathological significance; abolishes
FT ACACA binding and strongly reduces BRIP1
FT binding). {ECO:0000269|PubMed:10486320,
FT ECO:0000269|PubMed:11301010,
FT ECO:0000269|PubMed:15133502}.
FT /FTId=VAR_007798.
FT VARIANT 1753 1753 R -> T (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070510.
FT VARIANT 1764 1764 L -> P (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_063908.
FT VARIANT 1766 1766 I -> S (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331}.
FT /FTId=VAR_063909.
FT VARIANT 1767 1767 C -> S (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070511.
FT VARIANT 1770 1770 G -> V (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070512.
FT VARIANT 1775 1775 M -> K (in BC; strongly reduced
FT transcription transactivation; abolishes
FT interaction with BRIP1 and RBBP8).
FT {ECO:0000269|PubMed:18285836}.
FT /FTId=VAR_063212.
FT VARIANT 1775 1775 M -> R (in BC; alters protein stability
FT and abolishes ACACA and BRIP1 binding).
FT {ECO:0000269|PubMed:11301010,
FT ECO:0000269|PubMed:12427738,
FT ECO:0000269|PubMed:15133502,
FT ECO:0000269|PubMed:7545954,
FT ECO:0000269|PubMed:7939630}.
FT /FTId=VAR_007799.
FT VARIANT 1776 1776 P -> S (in ovarian cancer; unknown
FT pathological significance;
FT dbSNP:rs1800757).
FT /FTId=VAR_008764.
FT VARIANT 1782 1782 W -> C (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070513.
FT VARIANT 1786 1786 L -> P (in BROVCA1; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:12938098}.
FT /FTId=VAR_020704.
FT VARIANT 1788 1788 G -> V (in BC; unknown pathological
FT significance).
FT {ECO:0000269|PubMed:17924331}.
FT /FTId=VAR_063910.
FT VARIANT 1789 1789 A -> T (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070514.
FT VARIANT 1794 1794 E -> D (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070515.
FT VARIANT 1804 1804 V -> D (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070516.
FT VARIANT 1812 1812 P -> R (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070517.
FT VARIANT 1812 1812 P -> S (in ovarian cancer; unknown
FT pathological significance;
FT dbSNP:rs1800751).
FT /FTId=VAR_008765.
FT VARIANT 1837 1837 W -> R (in BC; unknown pathological
FT significance; functionally impaired in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070518.
FT VARIANT 1862 1862 H -> L (in BC; unknown pathological
FT significance; functionally neutral in
FT vitro). {ECO:0000269|PubMed:23867111}.
FT /FTId=VAR_070519.
FT MUTAGEN 26 26 I->A: Disrupts the interaction with E2
FT enzymes, thereby abolishing the E3
FT ubiquitin-protein ligase activity.
FT {ECO:0000269|PubMed:16818604,
FT ECO:0000269|PubMed:20351172}.
FT MUTAGEN 26 26 I->E: No ubiquitination of RBBP8. No
FT restoration RBBP8-mediated focus
FT formation or G2/M checkpoint control upon
FT DNA damage. {ECO:0000269|PubMed:16818604,
FT ECO:0000269|PubMed:20351172}.
FT MUTAGEN 71 71 R->G: No effect on interaction with BAP1.
FT {ECO:0000269|PubMed:9528852}.
FT MUTAGEN 308 308 S->N: Abolishes phosphorylation by AURKA
FT and interferes with cell cycle
FT progression from G2 to mitosis.
FT {ECO:0000269|PubMed:14990569}.
FT MUTAGEN 1143 1143 S->A: Reduces in vitro phosphorylation by
FT ATR. {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1239 1239 S->A: No effect on in vitro
FT phosphorylation by ATR.
FT {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1280 1280 S->A: Reduces in vitro phosphorylation by
FT ATR. {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1298 1298 S->A: No effect on in vitro
FT phosphorylation by ATR.
FT {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1330 1330 S->A: No effect on in vitro
FT phosphorylation by ATR.
FT {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1387 1387 S->A: Loss of IR-induced S-phase
FT checkpoint. Reduces in vitro
FT phosphorylation by ATR.
FT {ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:12183412}.
FT MUTAGEN 1394 1394 T->A: Reduces in vitro phosphorylation by
FT ATR. {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1423 1423 S->A: Inhibition of the infrared-induced
FT G2 arrest. Reduces phosphorylation by
FT ATR. {ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:12183412}.
FT MUTAGEN 1457 1457 S->A: Reduces in vitro phosphorylation by
FT ATR. {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1466 1466 S->A: No effect on in vitro
FT phosphorylation by ATR.
FT {ECO:0000269|PubMed:11114888}.
FT MUTAGEN 1524 1524 S->A: No change in infrared S-phase
FT delay; when associated with A-1387. No
FT effect on in vitro phosphorylation by
FT ATR. {ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:12183412}.
FT MUTAGEN 1655 1655 S->A: Abolishes interaction with BRIP1.
FT {ECO:0000269|PubMed:15133502}.
FT MUTAGEN 1702 1702 K->M: Abolishes interaction with BRIP1.
FT {ECO:0000269|PubMed:15133502}.
FT MUTAGEN 1738 1738 G->E: Abolishes interaction with BRIP1.
FT {ECO:0000269|PubMed:15133502}.
FT MUTAGEN 1755 1755 S->A: No effect on in vitro
FT phosphorylation by ATR.
FT {ECO:0000269|PubMed:11114888}.
FT CONFLICT 89 89 I -> T (in Ref. 4; AAB61673).
FT {ECO:0000305}.
FT CONFLICT 148 148 Missing (in Ref. 4; AAB61673).
FT {ECO:0000305}.
FT CONFLICT 253 253 A -> V (in Ref. 3; AAC00049).
FT {ECO:0000305}.
FT CONFLICT 713 713 S -> P (in Ref. 8; AAI15038).
FT {ECO:0000305}.
FT CONFLICT 1077 1077 G -> R (in Ref. 4; AAB61673).
FT {ECO:0000305}.
FT CONFLICT 1426 1426 S -> P (in Ref. 3; AAC00049).
FT {ECO:0000305}.
FT CONFLICT 1527 1527 E -> G (in Ref. 8; AAI15038).
FT {ECO:0000305}.
FT HELIX 3 5 {ECO:0000244|PDB:1JM7}.
FT HELIX 8 21 {ECO:0000244|PDB:1JM7}.
FT STRAND 25 27 {ECO:0000244|PDB:1JM7}.
FT HELIX 46 53 {ECO:0000244|PDB:1JM7}.
FT STRAND 54 58 {ECO:0000244|PDB:1JM7}.
FT TURN 62 64 {ECO:0000244|PDB:1JM7}.
FT TURN 70 72 {ECO:0000244|PDB:1JM7}.
FT STRAND 78 80 {ECO:0000244|PDB:1JM7}.
FT HELIX 81 96 {ECO:0000244|PDB:1JM7}.
FT STRAND 1651 1656 {ECO:0000244|PDB:4IGK}.
FT HELIX 1659 1671 {ECO:0000244|PDB:4IGK}.
FT STRAND 1675 1679 {ECO:0000244|PDB:1T29}.
FT STRAND 1686 1689 {ECO:0000244|PDB:4IGK}.
FT STRAND 1695 1697 {ECO:0000244|PDB:4IGK}.
FT HELIX 1701 1708 {ECO:0000244|PDB:4IGK}.
FT STRAND 1712 1715 {ECO:0000244|PDB:4IGK}.
FT HELIX 1717 1725 {ECO:0000244|PDB:4IGK}.
FT HELIX 1731 1734 {ECO:0000244|PDB:4IGK}.
FT TURN 1740 1742 {ECO:0000244|PDB:4IGK}.
FT STRAND 1743 1745 {ECO:0000244|PDB:1T29}.
FT HELIX 1748 1754 {ECO:0000244|PDB:4IGK}.
FT TURN 1755 1757 {ECO:0000244|PDB:1T29}.
FT TURN 1760 1763 {ECO:0000244|PDB:4IGK}.
FT STRAND 1765 1768 {ECO:0000244|PDB:4IGK}.
FT STRAND 1770 1772 {ECO:0000244|PDB:1T2V}.
FT STRAND 1773 1775 {ECO:0000244|PDB:4IGK}.
FT HELIX 1777 1786 {ECO:0000244|PDB:4IGK}.
FT STRAND 1790 1794 {ECO:0000244|PDB:4IGK}.
FT HELIX 1795 1797 {ECO:0000244|PDB:4IGK}.
FT STRAND 1801 1803 {ECO:0000244|PDB:4IGK}.
FT STRAND 1806 1810 {ECO:0000244|PDB:4IGK}.
FT HELIX 1812 1814 {ECO:0000244|PDB:4IGK}.
FT STRAND 1817 1819 {ECO:0000244|PDB:1OQA}.
FT HELIX 1820 1822 {ECO:0000244|PDB:4IGK}.
FT HELIX 1824 1827 {ECO:0000244|PDB:4IGK}.
FT STRAND 1828 1830 {ECO:0000244|PDB:3PXE}.
FT STRAND 1832 1834 {ECO:0000244|PDB:4IGK}.
FT HELIX 1835 1844 {ECO:0000244|PDB:4IGK}.
FT HELIX 1851 1853 {ECO:0000244|PDB:4IGK}.
SQ SEQUENCE 1863 AA; 207721 MW; 89C6D83FF56312AF CRC64;
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ
PSNNDLNTTE KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER KEWNKQKLPC
SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD GESESNAKVA DVLDVLNEVD
EYSGSSEKID LLASDPHEAL ICKSERVHSK SVESNIEDKI FGKTYRKKAS LPNLSHVTEN
LIIGAFVTEP QIIQERPLTN KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE
QNGQVMNITN SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI KKKKYNQMPV
RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL KLTNAPGSFT KCSNTSELKE
FVNPSLPREE KEEKLETVKV SNNAEDPKDL MLSGERVLQT ERSVESSSIS LVPGTDYGTQ
ESISLLEVST LGKAKTEPNK CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS
RETSIEMEES ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT
FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS RFCLSSQFRG
NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE ENFEEHSMSP EREMGNENIP
STVSTISRNN IRENVFKEAS SSNINEVGSS TNEVGSSINE IGSSDENIQA ELGRNRGPKL
NAMLRLGVLQ PEVYKQSLPG SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS
HASQVCSETP DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE CLSKNTEENL
LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC SELEDLTANT NTQDPFLIGS
SKQMRHQSES QGVGLSDKEL VSDDEERGTG LEENNQEEQS MDSNLGEAAS GCESETSVSE
DCSGLSSQSD ILTTQQRDTM QHNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE
DLRNPEQSTS EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET SYLPRQDLEG
TPYLESGISL FSDDPESDPS EDRAPESARV GNIPSSTSAL KVPQLKVAES AQSPAAAHTT
DTAGYNAMEE SVSREKPELT ASTERVNKRM SMVVSGLTPE EFMLVYKFAR KHHITLTNLI
TEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV
VNGRNHQGPK RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH
SHY
//
ID CBX4_HUMAN Reviewed; 560 AA.
AC O00257; B1PJR7; Q6TPI8; Q96C04;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 3.
DT 11-NOV-2015, entry version 153.
DE RecName: Full=E3 SUMO-protein ligase CBX4;
DE EC=6.3.2.-;
DE AltName: Full=Chromobox protein homolog 4;
DE AltName: Full=Polycomb 2 homolog;
DE Short=Pc2;
DE Short=hPc2;
GN Name=CBX4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=9315667;
RA Satijn D.P.E., Olson D.J., van der Vlag J., Hamer K.M., Lambrechts C.,
RA Masselink H., Gunster M.J., Sewalt R.G.A.B., van Driel R., Otte A.P.;
RT "Interference with the expression of a novel human polycomb protein,
RT hPc2, results in cellular transformation and apoptosis.";
RL Mol. Cell. Biol. 17:6076-6086(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=19266028; DOI=10.1371/journal.pgen.1000397;
RA Salichs E., Ledda A., Mularoni L., Alba M.M., de la Luna S.;
RT "Genome-wide analysis of histidine repeats reveals their role in the
RT localization of human proteins to the nuclear speckles compartment.";
RL PLoS Genet. 5:E1000397-E1000397(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Liu M., Cheng J., Wang L.;
RT "Cloning and identification of NS5ATP1-binding protein 16.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 457-560 (ISOFORM 1).
RX PubMed=9199346;
RA Satijn D.P.E., Gunster M.J., van der Vlag J., Hamer K.M., Schul W.,
RA Alkema M.J., Saurin A.J., Freemont P.S., van Driel R., Otte A.P.;
RT "RING1 is associated with the polycomb group protein complex and acts
RT as a transcriptional repressor.";
RL Mol. Cell. Biol. 17:4105-4113(1997).
RN [7]
RP INTERACTION WITH SUV39H1.
RX PubMed=12101246; DOI=10.1128/MCB.22.15.5539-5553.2002;
RA Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L.,
RA Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P.;
RT "Selective interactions between vertebrate polycomb homologs and the
RT SUV39H1 histone lysine methyltransferase suggest that histone H3-K9
RT methylation contributes to chromosomal targeting of Polycomb group
RT proteins.";
RL Mol. Cell. Biol. 22:5539-5553(2002).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A PRC1-LIKE
RP HPRC-H COMPLEX WITH BMI1; CBX2; CBX8; PHC1; PHC2; PHC3; RING1 AND
RP RNF2.
RX PubMed=12167701; DOI=10.1128/MCB.22.17.6070-6078.2002;
RA Levine S.S., Weiss A., Erdjument-Bromage H., Shao Z., Tempst P.,
RA Kingston R.E.;
RT "The core of the polycomb repressive complex is compositionally and
RT functionally conserved in flies and humans.";
RL Mol. Cell. Biol. 22:6070-6078(2002).
RN [9]
RP FUNCTION, SUMOYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=12679040; DOI=10.1016/S0092-8674(03)00159-4;
RA Kagey M.H., Melhuish T.A., Wotton D.;
RT "The polycomb protein Pc2 is a SUMO E3.";
RL Cell 113:127-137(2003).
RN [10]
RP SUMOYLATION AT LYS-494.
RX PubMed=15592428; DOI=10.1038/sj.emboj.7600506;
RA Kagey M.H., Melhuish T.A., Powers S.E., Wotton D.;
RT "Multiple activities contribute to Pc2 E3 function.";
RL EMBO J. 24:108-119(2005).
RN [11]
RP FUNCTION.
RX PubMed=16061479; DOI=10.1074/jbc.M504477200;
RA Long J., Zuo D., Park M.;
RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates
RT transcriptional repression of E-cadherin.";
RL J. Biol. Chem. 280:35477-35489(2005).
RN [12]
RP FUNCTION, INTERACTION WITH HIPK2, SUMOYLATION, SUBCELLULAR LOCATION,
RP AND PHOSPHORYLATION AT THR-497.
RX PubMed=17018294; DOI=10.1016/j.molcel.2006.08.004;
RA Roscic A., Moeller A., Calzado M.A., Renner F., Wimmer V.C.,
RA Gresko E., Luedi K.S., Schmitz M.L.;
RT "Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by
RT its substrate protein HIPK2.";
RL Mol. Cell 24:77-89(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION IN A PRC1-LIKE COMPLEX.
RX PubMed=19636380; DOI=10.1371/journal.pone.0006380;
RA Maertens G.N., El Messaoudi-Aubert S., Racek T., Stock J.K.,
RA Nicholls J., Rodriguez-Niedenfuhr M., Gil J., Peters G.;
RT "Several distinct polycomb complexes regulate and co-localize on the
RT INK4a tumor suppressor locus.";
RL PLoS ONE 4:E6380-E6380(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-149, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY (ISOFORM 2),
RP IDENTIFICATION IN A PRC1-LIKE COMPLEX, SELF-ASSOCIATION, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF SER-434.
RX PubMed=21282530; DOI=10.1074/mcp.M110.002642;
RA Vandamme J., Volkel P., Rosnoblet C., Le Faou P., Angrand P.O.;
RT "Interaction proteomics analysis of polycomb proteins defines distinct
RT PRC1 Complexes in mammalian cells.";
RL Mol. Cell. Proteomics 0:0-0(2011).
RN [17]
RP FUNCTION IN ZNF131 SUMOYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF LYS-494 AND THR-497.
RX PubMed=22467880; DOI=10.1074/jbc.M111.336354;
RA Oh Y., Chung K.C.;
RT "Small ubiquitin-like modifier (SUMO) modification of zinc finger
RT protein 131 potentiates its negative effect on estrogen signaling.";
RL J. Biol. Chem. 287:17517-17529(2012).
RN [18]
RP FUNCTION.
RX PubMed=22825850; DOI=10.1074/jbc.M112.390120;
RA Pelisch F., Pozzi B., Risso G., Munoz M.J., Srebrow A.;
RT "DNA damage-induced heterogeneous nuclear ribonucleoprotein K
RT SUMOylation regulates p53 transcriptional activation.";
RL J. Biol. Chem. 287:30789-30799(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-467, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-106; LYS-114; LYS-149;
RP LYS-205; LYS-212 AND LYS-280, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [21]
RP STRUCTURE BY NMR OF 8-65.
RG Structural genomics consortium (SGC);
RT "Solution NMR structure of the chromo domain of the chromobox protein
RT homolog 4.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) OF 8-62.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human chromobox homolog 4 (cbx4).";
RL Submitted (SEP-2009) to the PDB data bank.
CC -!- FUNCTION: E3 SUMO-protein ligase which facilitates SUMO1
CC conjugation by UBE2I. Involved in the sumoylation of HNRNPK, a
CC p53/TP53 transcriptional coactivator, hence indirectly regulates
CC p53/TP53 transcriptional activation resulting in p21/CDKN1A
CC expression. Monosumoylates ZNF131.
CC -!- FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1-
CC like complex, a complex class required to maintain the
CC transcriptionally repressive state of many genes, including Hox
CC genes, throughout development. PcG PRC1 complex acts via chromatin
CC remodeling and modification of histones; it mediates
CC monoubiquitination of histone H2A 'Lys-119', rendering chromatin
CC heritably changed in its expressibility.
CC -!- PATHWAY: Protein modification; protein sumoylation.
CC -!- SUBUNIT: Interacts with histone H3-K9Me3. Interacts with CHTOP (By
CC similarity). Component of a PRC1-like complex. Self-associates.
CC Interacts with SUV39H1 and HIPK2. Interacts with CSNK2B.
CC {ECO:0000250, ECO:0000269|PubMed:12101246,
CC ECO:0000269|PubMed:12167701, ECO:0000269|PubMed:17018294,
CC ECO:0000269|PubMed:19636380, ECO:0000269|PubMed:21282530}.
CC -!- INTERACTION:
CC P35226:BMI1; NbExp=4; IntAct=EBI-722425, EBI-2341576;
CC P68400:CSNK2A1; NbExp=2; IntAct=EBI-4392727, EBI-347804;
CC P67870:CSNK2B; NbExp=2; IntAct=EBI-4392727, EBI-348169;
CC Q16665:HIF1A; NbExp=15; IntAct=EBI-722425, EBI-447269;
CC Q9BYE7:PCGF6; NbExp=2; IntAct=EBI-4392727, EBI-1048026;
CC Q99496:RNF2; NbExp=2; IntAct=EBI-4392727, EBI-722416;
CC P31946:YWHAB; NbExp=2; IntAct=EBI-722425, EBI-359815;
CC P62258:YWHAE; NbExp=2; IntAct=EBI-4392727, EBI-356498;
CC P63104:YWHAZ; NbExp=2; IntAct=EBI-4392727, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Note=Localization
CC to nuclear polycomb bodies is required for ZNF131 sumoylation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00257-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00257-3; Sequence=VSP_041599;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The polyhistidine repeat may act as a targeting signal to
CC nuclear speckles. {ECO:0000269|PubMed:19266028}.
CC -!- PTM: Phosphorylated on Thr-497 by HIPK2 upon DNA damage. This
CC phosphorylation stimulates E3 SUMO-protein ligase activity and
CC promotes sumoylation on Lys-494, as well as sumoylation of other
CC target proteins, such as HNRNPK. {ECO:0000269|PubMed:12679040,
CC ECO:0000269|PubMed:15592428, ECO:0000269|PubMed:17018294}.
CC -!- MISCELLANEOUS: The human orthologs of the Drosophila Polycomb
CC group protein Pc are CBX2, CBX4, CBX6, CBX7 and CBX8. These show
CC distinct nuclear localizations, contribute differently to
CC transcriptional repression, and appear to be part of distinct
CC PRC1-like protein complexes. The hPRC-H complex purified in
CC PubMed:12167701 probably presents a mixture of different complexes
CC containing different Polycomb group proteins.
CC -!- SIMILARITY: Contains 1 chromo domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00053}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH14967.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AF013956; AAB80718.1; -; mRNA.
DR EMBL; EU439707; ACA49234.1; -; mRNA.
DR EMBL; AY390430; AAQ97596.1; -; mRNA.
DR EMBL; AC100791; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014967; AAH14967.1; ALT_SEQ; mRNA.
DR EMBL; U94344; AAB62734.1; -; mRNA.
DR CCDS; CCDS32758.1; -. [O00257-1]
DR RefSeq; NP_003646.2; NM_003655.2. [O00257-1]
DR UniGene; Hs.405046; -.
DR PDB; 2K28; NMR; -; A=8-65.
DR PDB; 3I8Z; X-ray; 1.51 A; A=8-62.
DR PDBsum; 2K28; -.
DR PDBsum; 3I8Z; -.
DR ProteinModelPortal; O00257; -.
DR SMR; O00257; 11-60.
DR BioGrid; 114105; 75.
DR DIP; DIP-42042N; -.
DR IntAct; O00257; 47.
DR MINT; MINT-1196265; -.
DR STRING; 9606.ENSP00000269397; -.
DR BindingDB; O00257; -.
DR ChEMBL; CHEMBL3232685; -.
DR PhosphoSite; O00257; -.
DR BioMuta; CBX4; -.
DR MaxQB; O00257; -.
DR PaxDb; O00257; -.
DR PRIDE; O00257; -.
DR Ensembl; ENST00000269397; ENSP00000269397; ENSG00000141582. [O00257-1]
DR GeneID; 8535; -.
DR KEGG; hsa:8535; -.
DR UCSC; uc002jxe.3; human. [O00257-1]
DR CTD; 8535; -.
DR GeneCards; CBX4; -.
DR H-InvDB; HIX0014237; -.
DR HGNC; HGNC:1554; CBX4.
DR HPA; HPA008228; -.
DR MIM; 603079; gene.
DR neXtProt; NX_O00257; -.
DR PharmGKB; PA26129; -.
DR eggNOG; ENOG410IPQ6; Eukaryota.
DR eggNOG; ENOG410ZQCR; LUCA.
DR GeneTree; ENSGT00530000063056; -.
DR HOGENOM; HOG000206923; -.
DR HOVERGEN; HBG005257; -.
DR InParanoid; O00257; -.
DR KO; K11452; -.
DR OMA; HHHHAVD; -.
DR OrthoDB; EOG7PCJGP; -.
DR PhylomeDB; O00257; -.
DR TreeFam; TF106456; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR UniPathway; UPA00886; -.
DR ChiTaRS; CBX4; human.
DR EvolutionaryTrace; O00257; -.
DR GenomeRNAi; 8535; -.
DR NextBio; 31968; -.
DR PRO; PR:O00257; -.
DR Proteomes; UP000005640; Chromosome 17.
DR Bgee; O00257; -.
DR CleanEx; HS_CBX4; -.
DR ExpressionAtlas; O00257; baseline and differential.
DR Genevisible; O00257; HS.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031519; C:PcG protein complex; IDA:UniProtKB.
DR GO; GO:0035102; C:PRC1 complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0003727; F:single-stranded RNA binding; IEA:Ensembl.
DR GO; GO:0032183; F:SUMO binding; IDA:MGI.
DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome.
DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IEA:Ensembl.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR InterPro; IPR000953; Chromo/shadow_dom.
DR InterPro; IPR017984; Chromo_dom_subgr.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR016197; Chromodomain-like.
DR InterPro; IPR023779; Chromodomain_CS.
DR Pfam; PF00385; Chromo; 1.
DR PRINTS; PR00504; CHROMODOMAIN.
DR SMART; SM00298; CHROMO; 1.
DR SUPFAM; SSF54160; SSF54160; 1.
DR PROSITE; PS00598; CHROMO_1; 1.
DR PROSITE; PS50013; CHROMO_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromatin regulator;
KW Complete proteome; Isopeptide bond; Ligase; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1 560 E3 SUMO-protein ligase CBX4.
FT /FTId=PRO_0000080206.
FT DOMAIN 11 69 Chromo. {ECO:0000255|PROSITE-
FT ProRule:PRU00053}.
FT REGION 1 539 Interaction with BMI1.
FT REGION 540 560 Interaction with RNF2.
FT COMPBIAS 378 400 His-rich.
FT COMPBIAS 389 400 Poly-His.
FT COMPBIAS 499 510 Poly-Ala.
FT MOD_RES 149 149 N6-acetyllysine; alternate.
FT {ECO:0000244|PubMed:19608861}.
FT MOD_RES 467 467 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 497 497 Phosphothreonine; by HIPK2.
FT {ECO:0000269|PubMed:17018294}.
FT CROSSLNK 106 106 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 114 114 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 149 149 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2);
FT alternate. {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 205 205 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 212 212 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 280 280 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 494 494 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 127 396 Missing (in isoform 2).
FT {ECO:0000303|Ref.3}.
FT /FTId=VSP_041599.
FT MUTAGEN 434 434 S->A: Abolishes interaction with YWHAZ
FT and YWHAE; impairs interaction with PCGF6
FT and BMI1; no effect on interaction with
FT RNF2. {ECO:0000269|PubMed:21282530}.
FT MUTAGEN 494 494 K->R: No effect on ZNF131 sumoylation.
FT {ECO:0000269|PubMed:22467880}.
FT MUTAGEN 497 497 T->A: Small decrease in ZNF131
FT sumoylation.
FT {ECO:0000269|PubMed:22467880}.
FT CONFLICT 137 138 Missing (in Ref. 1; AAB80718).
FT {ECO:0000305}.
FT CONFLICT 142 142 P -> R (in Ref. 1; AAB80718).
FT {ECO:0000305}.
FT CONFLICT 458 458 P -> R (in Ref. 1; AAB80718 and 5;
FT AAB62734). {ECO:0000305}.
FT CONFLICT 477 477 C -> S (in Ref. 1; AAB80718 and 5;
FT AAB62734). {ECO:0000305}.
FT CONFLICT 480 480 T -> S (in Ref. 1; AAB80718 and 5;
FT AAB62734). {ECO:0000305}.
FT CONFLICT 505 505 V -> VAA (in Ref. 3; ACA49234).
FT {ECO:0000305}.
FT STRAND 13 22 {ECO:0000244|PDB:3I8Z}.
FT STRAND 25 32 {ECO:0000244|PDB:3I8Z}.
FT HELIX 37 39 {ECO:0000244|PDB:3I8Z}.
FT STRAND 41 44 {ECO:0000244|PDB:3I8Z}.
FT HELIX 45 48 {ECO:0000244|PDB:3I8Z}.
FT HELIX 51 53 {ECO:0000244|PDB:3I8Z}.
SQ SEQUENCE 560 AA; 61368 MW; DF5C8C4C0CCB1F31 CRC64;
MELPAVGEHV FAVESIEKKR IRKGRVEYLV KWRGWSPKYN TWEPEENILD PRLLIAFQNR
ERQEQLMGYR KRGPKPKPLV VQVPTFARRS NVLTGLQDSS TDNRAKLDLG AQGKGQGHQY
ELNSKKHHQY QPHSKERAGK PPPPGKSGKY YYQLNSKKHH PYQPDPKMYD LQYQGGHKEA
PSPTCPDLGA KSHPPDKWAQ GAGAKGYLGA VKPLAGAAGA PGKGSEKGPP NGMMPAPKEA
VTGNGIGGKM KIVKNKNKNG RIVIVMSKYM ENGMQAVKIK SGEVAEGEAR SPSHKKRAAD
ERHPPADRTF KKAAGAEEKK VEAPPKRREE EVSGVSDPQP QDAGSRKLSP TKEAFGEQPL
QLTTKPDLLA WDPARNTHPP SHHPHPHPHH HHHHHHHHHH AVGLNLSHVR KRCLSETHGE
REPCKKRLTA RSISTPTCLG GSPAAERPAD LPPAAALPQP EVILLDSDLD EPIDLRCVKT
RSEAGEPPSS LQVKPETPAS AAVAVAAAAA PTTTAEKPPA EAQDEPAESL SEFKPFFGNI
IITDVTANCL TVTFKEYVTV
//
ID CHD3_HUMAN Reviewed; 2000 AA.
AC Q12873; D3DTQ9; E9PG89; Q9Y4I0;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 3.
DT 11-NOV-2015, entry version 169.
DE RecName: Full=Chromodomain-helicase-DNA-binding protein 3;
DE Short=CHD-3;
DE EC=3.6.4.12;
DE AltName: Full=ATP-dependent helicase CHD3;
DE AltName: Full=Mi-2 autoantigen 240 kDa protein;
DE AltName: Full=Mi2-alpha;
DE AltName: Full=Zinc finger helicase;
DE Short=hZFH;
GN Name=CHD3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=9688266; DOI=10.1046/j.1432-1327.1998.2540558.x;
RA Aubry F., Mattei M.-G., Galibert F.;
RT "Identification of a human 17p-located cDNA encoding a protein of the
RT Snf2-like helicase family.";
RL Eur. J. Biochem. 254:558-564(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1966 (ISOFORM 2).
RC TISSUE=Fetus;
RX PubMed=9326634; DOI=10.1073/pnas.94.21.11472;
RA Woodage T., Basrai M.A., Baxevanis A.D., Hieter P., Collins F.S.;
RT "Characterization of the CHD family of proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:11472-11477(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 121-654.
RC TISSUE=Thymus;
RX PubMed=7560064; DOI=10.1172/JCI118218;
RA Ge Q., Nilasena D.S., O'Brien C.A., Frank M.B., Targoff I.N.;
RT "Molecular analysis of a major antigenic region of the 240 kD protein
RT of Mi-2 autoantigen.";
RL J. Clin. Invest. 96:1730-1737(1995).
RN [6]
RP IDENTIFICATION AS A COMPONENT OF THE NURD COMPLEX, AND FUNCTION.
RX PubMed=9804427; DOI=10.1038/27699;
RA Tong J.K., Hassig C.A., Schnitzler G.R., Kingston R.E.,
RA Schreiber S.L.;
RT "Chromatin deacetylation by an ATP-dependent nucleosome remodelling
RT complex.";
RL Nature 395:917-921(1998).
RN [7]
RP INTERACTION WITH TRIM28.
RX PubMed=11230151; DOI=10.1101/gad.869501;
RA Schultz D.C., Friedman J.R., Rauscher F.J. III;
RT "Targeting histone deacetylase complexes via KRAB-zinc finger
RT proteins: the PHD and bromodomains of KAP-1 form a cooperative unit
RT that recruits a novel isoform of the Mi-2alpha subunit of NuRD.";
RL Genes Dev. 15:428-443(2001).
RN [8]
RP INTERACTION WITH HABP4 AND SERBP1.
RX PubMed=12505151; DOI=10.1016/S0014-5793(02)03737-7;
RA Lemos T.A., Passos D.O., Nery F.C., Kobarg J.;
RT "Characterization of a new family of proteins that interact with the
RT C-terminal region of the chromatin-remodeling factor CHD-3.";
RL FEBS Lett. 533:14-20(2003).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-1601 AND
RP SER-1605, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [10]
RP INTERACTION WITH PCNT, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=17626165; DOI=10.1091/mbc.E06-07-0604;
RA Sillibourne J.E., Delaval B., Redick S., Sinha M., Doxsey S.J.;
RT "Chromatin remodeling proteins interact with pericentrin to regulate
RT centrosome integrity.";
RL Mol. Biol. Cell 18:3667-3680(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1601, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-713; SER-1367; SER-1601
RP AND SER-1605, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-713; SER-1601 AND
RP SER-1605, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1601 AND SER-1605, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1601, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1308, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
CC -!- FUNCTION: Component of the histone deacetylase NuRD complex which
CC participates in the remodeling of chromatin by deacetylating
CC histones. Required for anchoring centrosomal pericentrin in both
CC interphase and mitosis, for spindle organization and centrosome
CC integrity. {ECO:0000269|PubMed:17626165,
CC ECO:0000269|PubMed:9804427}.
CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
CC -!- SUBUNIT: Central component of the nucleosome remodeling and
CC histone deacetylase (NuRD) repressive complex. Interacts with
CC TRIM28 and SERBP1. Interacts (via its C-terminal) with HABP4.
CC Interacts with PCNT; the interaction regulates centrosome
CC integrity. {ECO:0000269|PubMed:11230151,
CC ECO:0000269|PubMed:12505151, ECO:0000269|PubMed:17626165}.
CC -!- INTERACTION:
CC Q99728:BARD1; NbExp=2; IntAct=EBI-523590, EBI-473181;
CC P17844:DDX5; NbExp=4; IntAct=EBI-523590, EBI-351962;
CC Q9Y2X7:GIT1; NbExp=2; IntAct=EBI-523590, EBI-466061;
CC P42858:HTT; NbExp=3; IntAct=EBI-523590, EBI-466029;
CC O60341:KDM1A; NbExp=4; IntAct=EBI-523590, EBI-710124;
CC O75400:PRPF40A; NbExp=2; IntAct=EBI-523590, EBI-473291;
CC Q8NC51:SERBP1; NbExp=5; IntAct=EBI-523590, EBI-523558;
CC P61956:SUMO2; NbExp=3; IntAct=EBI-523590, EBI-473220;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17626165}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:17626165}. Note=Associates with centrosomes in
CC interphase and mitosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q12873-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q12873-2; Sequence=VSP_017231;
CC Name=3;
CC IsoId=Q12873-3; Sequence=VSP_047097;
CC Note=No experimental confirmation available. Gene prediction
CC based on EST data.;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC {ECO:0000269|PubMed:9688266}.
CC -!- MISCELLANEOUS: One of the main antigens reacting with anti-MI-2
CC positive sera of dermatomyositis.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family.
CC {ECO:0000305}.
CC -!- SIMILARITY: Contains 2 chromo domains. {ECO:0000255|PROSITE-
CC ProRule:PRU00053}.
CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00541}.
CC -!- SIMILARITY: Contains 1 helicase C-terminal domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00542}.
CC -!- SIMILARITY: Contains 2 PHD-type zinc fingers.
CC {ECO:0000255|PROSITE-ProRule:PRU00146}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB87383.1; Type=Miscellaneous discrepancy; Note=Differs from position 1967 onward for unknown reasons.; Evidence={ECO:0000305};
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DR EMBL; U91543; AAC39923.1; -; mRNA.
DR EMBL; AC104581; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90114.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90116.1; -; Genomic_DNA.
DR EMBL; AF006515; AAB87383.1; ALT_TERM; mRNA.
DR EMBL; U08379; AAC50228.1; -; mRNA.
DR CCDS; CCDS32553.2; -. [Q12873-3]
DR CCDS; CCDS32554.1; -. [Q12873-1]
DR CCDS; CCDS32555.1; -. [Q12873-2]
DR RefSeq; NP_001005271.2; NM_001005271.2. [Q12873-3]
DR RefSeq; NP_001005273.1; NM_001005273.2. [Q12873-1]
DR RefSeq; NP_005843.2; NM_005852.3. [Q12873-2]
DR UniGene; Hs.25601; -.
DR ProteinModelPortal; Q12873; -.
DR SMR; Q12873; 374-429, 453-686.
DR BioGrid; 107532; 135.
DR DIP; DIP-32496N; -.
DR IntAct; Q12873; 97.
DR MINT; MINT-1185641; -.
DR STRING; 9606.ENSP00000369716; -.
DR PhosphoSite; Q12873; -.
DR BioMuta; CHD3; -.
DR DMDM; 88911273; -.
DR MaxQB; Q12873; -.
DR PaxDb; Q12873; -.
DR PRIDE; Q12873; -.
DR Ensembl; ENST00000330494; ENSP00000332628; ENSG00000170004. [Q12873-1]
DR Ensembl; ENST00000358181; ENSP00000350907; ENSG00000170004. [Q12873-2]
DR Ensembl; ENST00000380358; ENSP00000369716; ENSG00000170004. [Q12873-3]
DR GeneID; 1107; -.
DR KEGG; hsa:1107; -.
DR UCSC; uc002gje.2; human. [Q12873-1]
DR UCSC; uc002gjf.2; human. [Q12873-2]
DR CTD; 1107; -.
DR GeneCards; CHD3; -.
DR H-InvDB; HIX0013516; -.
DR HGNC; HGNC:1918; CHD3.
DR HPA; HPA043368; -.
DR MIM; 602120; gene.
DR neXtProt; NX_Q12873; -.
DR PharmGKB; PA26454; -.
DR eggNOG; KOG0383; Eukaryota.
DR eggNOG; COG0553; LUCA.
DR GeneTree; ENSGT00760000119067; -.
DR HOGENOM; HOG000231124; -.
DR HOVERGEN; HBG005326; -.
DR InParanoid; Q12873; -.
DR KO; K11642; -.
DR OMA; GKGPGYK; -.
DR OrthoDB; EOG7C8GG7; -.
DR PhylomeDB; Q12873; -.
DR TreeFam; TF106448; -.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR ChiTaRS; CHD3; human.
DR GeneWiki; CHD3; -.
DR GenomeRNAi; 1107; -.
DR NextBio; 4590; -.
DR PRO; PR:Q12873; -.
DR Proteomes; UP000005640; Chromosome 17.
DR Bgee; Q12873; -.
DR CleanEx; HS_CHD3; -.
DR ExpressionAtlas; Q12873; baseline and differential.
DR Genevisible; Q12873; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016581; C:NuRD complex; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004003; F:ATP-dependent DNA helicase activity; TAS:ProtInc.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0004386; F:helicase activity; NAS:UniProtKB.
DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0051297; P:centrosome organization; IDA:UniProtKB.
DR GO; GO:0006333; P:chromatin assembly or disassembly; IEA:Ensembl.
DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; TAS:Reactome.
DR GO; GO:0032508; P:DNA duplex unwinding; TAS:GOC.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0007051; P:spindle organization; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR Gene3D; 1.10.30.10; -; 1.
DR Gene3D; 3.30.40.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR028722; CHD3.
DR InterPro; IPR012957; CHD_C2.
DR InterPro; IPR012958; CHD_N.
DR InterPro; IPR000953; Chromo/shadow_dom.
DR InterPro; IPR023780; Chromo_domain.
DR InterPro; IPR016197; Chromodomain-like.
DR InterPro; IPR023779; Chromodomain_CS.
DR InterPro; IPR002464; DNA/RNA_helicase_DEAH_CS.
DR InterPro; IPR009462; DUF1086.
DR InterPro; IPR009463; DUF1087.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000330; SNF2_N.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR10799:SF544; PTHR10799:SF544; 4.
DR Pfam; PF08074; CHDCT2; 1.
DR Pfam; PF08073; CHDNT; 1.
DR Pfam; PF00385; Chromo; 1.
DR Pfam; PF06461; DUF1086; 1.
DR Pfam; PF06465; DUF1087; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF00628; PHD; 2.
DR Pfam; PF00176; SNF2_N; 1.
DR SMART; SM00298; CHROMO; 2.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SMART; SM00249; PHD; 2.
DR SMART; SM00184; RING; 2.
DR SUPFAM; SSF47095; SSF47095; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF54160; SSF54160; 3.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS00598; CHROMO_1; 1.
DR PROSITE; PS50013; CHROMO_2; 2.
DR PROSITE; PS00690; DEAH_ATP_HELICASE; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
DR PROSITE; PS01359; ZF_PHD_1; 2.
DR PROSITE; PS50016; ZF_PHD_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chromatin regulator;
KW Complete proteome; Cytoplasm; Cytoskeleton; DNA-binding; Helicase;
KW Hydrolase; Isopeptide bond; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1 2000 Chromodomain-helicase-DNA-binding protein
FT 3.
FT /FTId=PRO_0000080227.
FT DOMAIN 494 594 Chromo 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00053}.
FT DOMAIN 631 673 Chromo 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00053}.
FT DOMAIN 748 932 Helicase ATP-binding.
FT {ECO:0000255|PROSITE-ProRule:PRU00541}.
FT DOMAIN 1064 1229 Helicase C-terminal.
FT {ECO:0000255|PROSITE-ProRule:PRU00542}.
FT ZN_FING 379 426 PHD-type 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00146}.
FT ZN_FING 456 503 PHD-type 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00146}.
FT NP_BIND 761 768 ATP. {ECO:0000255|PROSITE-
FT ProRule:PRU00541}.
FT REGION 1566 1966 Required for interaction with PCNT.
FT MOTIF 883 886 DEAH box.
FT COMPBIAS 206 221 Poly-Ala.
FT COMPBIAS 243 246 Poly-Pro.
FT COMPBIAS 355 358 Poly-Lys.
FT COMPBIAS 434 446 Poly-Glu.
FT COMPBIAS 697 703 Poly-Lys.
FT MOD_RES 308 308 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q14839}.
FT MOD_RES 324 324 Phosphoserine.
FT {ECO:0000244|PubMed:17081983}.
FT MOD_RES 376 376 Phosphothreonine.
FT {ECO:0000250|UniProtKB:Q14839}.
FT MOD_RES 713 713 Phosphoserine.
FT {ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:19690332}.
FT MOD_RES 1219 1219 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q6PDQ2}.
FT MOD_RES 1367 1367 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT MOD_RES 1532 1532 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q14839}.
FT MOD_RES 1538 1538 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q14839}.
FT MOD_RES 1601 1601 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:18691976,
FT ECO:0000244|PubMed:19690332,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:24275569}.
FT MOD_RES 1605 1605 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:19690332,
FT ECO:0000244|PubMed:20068231}.
FT CROSSLNK 1308 1308 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 1573 1573 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000250|UniProtKB:Q14839}.
FT VAR_SEQ 1 32 MKAADTVILWARSKNDQLRISFPPGLCWGDRM -> MASPL
FT RDEEEEEEEMVVSEEEEEEEEEGDEEEEEEVEAADEDDEED
FT DDEGVLGRGPGHDRGRDRHSPPGCHLFPPPPPPPPPLPPPP
FT PPPP (in isoform 3). {ECO:0000305}.
FT /FTId=VSP_047097.
FT VAR_SEQ 1642 1675 Missing (in isoform 2).
FT {ECO:0000303|PubMed:9326634,
FT ECO:0000303|PubMed:9688266}.
FT /FTId=VSP_017231.
FT VARIANT 3 3 A -> V (in dbSNP:rs931543).
FT /FTId=VAR_048728.
FT CONFLICT 121 126 GEGDGG -> PHFQQK (in Ref. 5; AAC50228).
FT {ECO:0000305}.
FT CONFLICT 309 312 Missing (in Ref. 5; AAC50228).
FT {ECO:0000305}.
FT CONFLICT 653 653 W -> G (in Ref. 5; AAC50228).
FT {ECO:0000305}.
FT CONFLICT 1704 1704 K -> N (in Ref. 1; AAC39923).
FT {ECO:0000305}.
SQ SEQUENCE 2000 AA; 226592 MW; 4494F56E5D0E7083 CRC64;
MKAADTVILW ARSKNDQLRI SFPPGLCWGD RMPDKDDIRL LPSALGVKKR KRGPKKQKEN
KPGKPRKRKK RDSEEEFGSE RDEYREKSES GGSEYGTGPG RKRRRKHREK KEKKTKRRKK
GEGDGGQKQV EQKSSATLLL TWGLEDVEHV FSEEDYHTLT NYKAFSQFMR PLIAKKNPKI
PMSKMMTILG AKWREFSANN PFKGSAAAVA AAAAAAAAAV AEQVSAAVSS ATPIAPSGPP
ALPPPPAADI QPPPIRRAKT KEGKGPGHKR RSKSPRVPDG RKKLRGKKMA PLKIKLGLLG
GKRKKGGSYV FQSDEGPEPE AEESDLDSGS VHSASGRPDG PVRTKKLKRG RPGRKKKKVL
GCPAVAGEEE VDGYETDHQD YCEVCQQGGE IILCDTCPRA YHLVCLDPEL DRAPEGKWSC
PHCEKEGVQW EAKEEEEEYE EEGEEEGEKE EEDDHMEYCR VCKDGGELLC CDACISSYHI
HCLNPPLPDI PNGEWLCPRC TCPVLKGRVQ KILHWRWGEP PVAVPAPQQA DGNPDVPPPR
PLQGRSEREF FVKWVGLSYW HCSWAKELQL EIFHLVMYRN YQRKNDMDEP PPLDYGSGED
DGKSDKRKVK DPHYAEMEEK YYRFGIKPEW MTVHRIINHS VDKKGNYHYL VKWRDLPYDQ
STWEEDEMNI PEYEEHKQSY WRHRELIMGE DPAQPRKYKK KKKELQGDGP PSSPTNDPTV
KYETQPRFIT ATGGTLHMYQ LEGLNWLRFS WAQGTDTILA DEMGLGKTIQ TIVFLYSLYK
EGHTKGPFLV SAPLSTIINW EREFQMWAPK FYVVTYTGDK DSRAIIRENE FSFEDNAIKG
GKKAFKMKRE AQVKFHVLLT SYELITIDQA ALGSIRWACL VVDEAHRLKN NQSKFFRVLN
GYKIDHKLLL TGTPLQNNLE ELFHLLNFLT PERFNNLEGF LEEFADISKE DQIKKLHDLL
GPHMLRRLKA DVFKNMPAKT ELIVRVELSP MQKKYYKYIL TRNFEALNSR GGGNQVSLLN
IMMDLKKCCN HPYLFPVAAM ESPKLPSGAY EGGALIKSSG KLMLLQKMLR KLKEQGHRVL
IFSQMTKMLD LLEDFLDYEG YKYERIDGGI TGALRQEAID RFNAPGAQQF CFLLSTRAGG
LGINLATADT VIIFDSDWNP HNDIQAFSRA HRIGQANKVM IYRFVTRASV EERITQVAKR
KMMLTHLVVR PGLGSKAGSM SKQELDDILK FGTEELFKDE NEGENKEEDS SVIHYDNEAI
ARLLDRNQDA TEDTDVQNMN EYLSSFKVAQ YVVREEDKIE EIEREIIKQE ENVDPDYWEK
LLRHHYEQQQ EDLARNLGKG KRVRKQVNYN DAAQEDQDNQ SEYSVGSEEE DEDFDERPEG
RRQSKRQLRN EKDKPLPPLL ARVGGNIEVL GFNTRQRKAF LNAVMRWGMP PQDAFTTQWL
VRDLRGKTEK EFKAYVSLFM RHLCEPGADG SETFADGVPR EGLSRQQVLT RIGVMSLVKK
KVQEFEHING RWSMPELMPD PSADSKRSSR ASSPTKTSPT TPEASATNSP CTSKPATPAP
SEKGEGIRTP LEKEEAENQE EKPEKNSRIG EKMETEADAP SPAPSLGERL EPRKIPLEDE
VPGVPGEMEP EPGYRGDREK SATESTPGER GEEKPLDGQE HRERPEGETG DLGKREDVKG
DRELRPGPRD EPRSNGRREE KTEKPRFMFN IADGGFTELH TLWQNEERAA ISSGKLNEIW
HRRHDYWLLA GIVLHGYARW QDIQNDAQFA IINEPFKTEA NKGNFLEMKN KFLARRFKLL
EQALVIEEQL RRAAYLNLSQ EPAHPAMALH ARFAEAECLA ESHQHLSKES LAGNKPANAV
LHKVLNQLEE LLSDMKADVT RLPATLSRIP PIAARLQMSE RSILSRLASK GTEPHPTPAY
PPGPYATPPG YGAAFSAAPV GALAAAGANY SQMPAGSFIT AATNGPPVLV KKEKEMVGAL
VSDGLDRKEP RAGEVICIDD
//
ID COM1_HUMAN Reviewed; 897 AA.
AC Q99708; A6NKN2; A8K8W6; E7ETY1; O75371; Q8NHQ3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 11-NOV-2015, entry version 147.
DE RecName: Full=DNA endonuclease RBBP8;
DE EC=3.1.-.-;
DE AltName: Full=CtBP-interacting protein;
DE Short=CtIP;
DE AltName: Full=Retinoblastoma-binding protein 8;
DE Short=RBBP-8;
DE AltName: Full=Retinoblastoma-interacting protein and myosin-like;
DE Short=RIM;
DE AltName: Full=Sporulation in the absence of SPO11 protein 2 homolog;
DE Short=SAE2;
GN Name=RBBP8; Synonyms=CTIP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH RB1.
RX PubMed=9721205; DOI=10.1006/geno.1998.5368;
RA Fusco C., Reymond A., Zervos A.S.;
RT "Molecular cloning and characterization of a novel retinoblastoma-
RT binding protein.";
RL Genomics 51:351-358(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH CTBP1.
RX PubMed=9535825; DOI=10.1074/jbc.273.15.8549;
RA Schaeper U., Subramanian T., Lim L., Boyd J.M., Chinnadurai G.;
RT "Interaction between a cellular protein that binds to the C-terminal
RT region of adenovirus E1A (CtBP) and a novel cellular protein is
RT disrupted by E1A through a conserved PLDLS motif.";
RL J. Biol. Chem. 273:8549-8552(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Endometrial cancer;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BRCA1.
RX PubMed=10764811; DOI=10.1074/jbc.M909494199;
RA Yu X., Baer R.;
RT "Nuclear localization and cell cycle-specific expression of CtIP, a
RT protein that associates with the BRCA1 tumor suppressor.";
RL J. Biol. Chem. 275:18541-18549(2000).
RN [9]
RP FUNCTION, PHOSPHORYLATION AT SER-664 AND SER-745, AND MUTAGENESIS OF
RP SER-664 AND SER-745.
RX PubMed=10910365; DOI=10.1038/35018134;
RA Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y.,
RA Lee E.Y.-H.P., Lee W.-H.;
RT "Functional link of BRCA1 and ataxia telangiectasia gene product in
RT DNA damage response.";
RL Nature 406:210-215(2000).
RN [10]
RP INTERACTION WITH LMO4.
RX PubMed=11751867; DOI=10.1074/jbc.M110603200;
RA Sum E.Y., Peng B., Yu X., Chen J., Byrne J., Lindeman G.J.,
RA Visvader J.E.;
RT "The LIM domain protein LMO4 interacts with the cofactor CtIP and the
RT tumor suppressor BRCA1 and inhibits BRCA1 activity.";
RL J. Biol. Chem. 277:7849-7856(2002).
RN [11]
RP INTERACTION WITH SIAH1, AND UBIQUITINATION.
RX PubMed=14654780; DOI=10.1038/sj.onc.1206994;
RA Germani A., Prabel A., Mourah S., Podgorniak M.-P., Di Carlo A.,
RA Ehrlich R., Gisselbrecht S., Varin-Blank N., Calvo F.,
RA Bruzzoni-Giovanelli H.;
RT "SIAH-1 interacts with CtIP and promotes its degradation by the
RT proteasome pathway.";
RL Oncogene 22:8845-8851(2003).
RN [12]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15084581; DOI=10.1074/jbc.M313974200;
RA Dubin M.J., Stokes P.H., Sum E.Y., Williams R.S., Valova V.A.,
RA Robinson P.J., Lindeman G.J., Glover J.N., Visvader J.E.,
RA Matthews J.M.;
RT "Dimerization of CtIP, a BRCA1- and CtBP-interacting protein, is
RT mediated by an N-terminal coiled-coil motif.";
RL J. Biol. Chem. 279:26932-26938(2004).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT SER-327, INTERACTION WITH BRCA1, AND
RP MUTAGENESIS OF SER-327.
RX PubMed=15485915; DOI=10.1128/MCB.24.21.9478-9486.2004;
RA Yu X., Chen J.;
RT "DNA damage-induced cell cycle checkpoint control requires CtIP, a
RT phosphorylation-dependent binding partner of BRCA1 C-terminal
RT domains.";
RL Mol. Cell. Biol. 24:9478-9486(2004).
RN [14]
RP INTERACTION WITH BRCA1, FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF
RP SER-327.
RX PubMed=16818604; DOI=10.1101/gad.1431006;
RA Yu X., Fu S., Lai M., Baer R., Chen J.;
RT "BRCA1 ubiquitinates its phosphorylation-dependent binding partner
RT CtIP.";
RL Genes Dev. 20:1721-1726(2006).
RN [15]
RP FUNCTION.
RX PubMed=16581787; DOI=10.1128/MCB.26.8.3124-3134.2006;
RA Liu F., Lee W.H.;
RT "CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway
RT during G1/S progression.";
RL Mol. Cell. Biol. 26:3124-3134(2006).
RN [16]
RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP BRCA1; MRE11A AND RAD50.
RX PubMed=17965729; DOI=10.1038/nature06337;
RA Sartori A.A., Lukas C., Coates J., Mistrik M., Fu S., Bartek J.,
RA Baer R., Lukas J., Jackson S.P.;
RT "Human CtIP promotes DNA end resection.";
RL Nature 450:509-514(2007).
RN [17]
RP ASSOCIATION WITH OVARIAN CANCER SURVIVAL.
RX PubMed=19270026; DOI=10.1093/hmg/ddp107;
RA Quaye L., Dafou D., Ramus S.J., Song H., Gentry-Maharaj A.,
RA Notaridou M., Hogdall E., Kjaer S.K., Christensen L., Hogdall C.,
RA Easton D.F., Jacobs I., Menon U., Pharoah P.D., Gayther S.A.;
RT "Functional complementation studies identify candidate genes and
RT common genetic variants associated with ovarian cancer survival.";
RL Hum. Mol. Genet. 18:1869-1878(2009).
RN [18]
RP FUNCTION, DNA-BINDING, PHOSPHORYLATION AT THR-847, AND MUTAGENESIS OF
RP THR-847.
RX PubMed=19202191; DOI=10.1074/jbc.M808906200;
RA Huertas P., Jackson S.P.;
RT "Human CtIP mediates cell cycle control of DNA end resection and
RT double strand break repair.";
RL J. Biol. Chem. 284:9558-9565(2009).
RN [19]
RP FUNCTION, INTERACTION WITH MRE11A; RAD50 AND NBN, AND MUTAGENESIS OF
RP HIS-31; VAL-35; LYS-41 AND LEU-45.
RX PubMed=19759395; DOI=10.1074/jbc.M109.023424;
RA Yuan J., Chen J.;
RT "N terminus of CtIP is critical for homologous recombination-mediated
RT double-strand break repair.";
RL J. Biol. Chem. 284:31746-31752(2009).
RN [20]
RP FUNCTION, AND MUTAGENESIS OF LYS-513 AND LYS-515.
RX PubMed=20064462; DOI=10.1016/j.molcel.2009.12.002;
RA You Z., Shi L.Z., Zhu Q., Wu P., Zhang Y.W., Basilio A., Tonnu N.,
RA Verma I.M., Berns M.W., Hunter T.;
RT "CtIP links DNA double-strand break sensing to resection.";
RL Mol. Cell 36:954-969(2009).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP FUNCTION, ACETYLATION AT LYS-432; LYS-526 AND LYS-604, INTERACTION
RP WITH SIRT6, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF
RP LYS-432; LYS-526 AND LYS-604.
RX PubMed=20829486; DOI=10.1126/science.1192049;
RA Kaidi A., Weinert B.T., Choudhary C., Jackson S.P.;
RT "Human SIRT6 promotes DNA end resection through CtIP deacetylation.";
RL Science 329:1348-1353(2010).
RN [24]
RP ASSOCIATION WITH BREAST CANCER.
RX PubMed=21799032; DOI=10.1158/0008-5472.CAN-11-0773;
RA Rebbeck T.R., Mitra N., Domchek S.M., Wan F., Friebel T.M., Tran T.V.,
RA Singer C.F., Tea M.K., Blum J.L., Tung N., Olopade O.I., Weitzel J.N.,
RA Lynch H.T., Snyder C.L., Garber J.E., Antoniou A.C., Peock S.,
RA Evans D.G., Paterson J., Kennedy M.J., Donaldson A., Dorkins H.,
RA Easton D.F., Rubinstein W.S., Daly M.B., Isaacs C., Nevanlinna H.,
RA Couch F.J., Andrulis I.L., Freidman E., Laitman Y., Ganz P.A.,
RA Tomlinson G.E., Neuhausen S.L., Narod S.A., Phelan C.M., Greenberg R.,
RA Nathanson K.L.;
RT "Modification of BRCA1-associated breast and ovarian cancer risk by
RT BRCA1-interacting genes.";
RL Cancer Res. 71:5792-5805(2011).
RN [25]
RP INVOLVEMENT IN JWDS, AND INVOLVEMENT IN SCKL2.
RX PubMed=21998596; DOI=10.1371/journal.pgen.1002310;
RA Jackson S.P., Borglum A.D.;
RT "CtIP mutations cause Seckel and Jawad syndromes.";
RL PLoS Genet. 7:E1002310-E1002310(2011).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-869, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
CC -!- FUNCTION: Endonuclease that cooperates with the MRE11-RAD50-NBN
CC (MRN) complex in processing meiotic and mitotic double-strand
CC breaks (DSBs) by ensuring both resection and intrachromosomal
CC association of the broken ends. Functions downstream of the MRN
CC complex and ATM, promotes ATR activation and its recruitment to
CC DSBs in the S/G2 phase facilitating the generation of ssDNA.
CC Component of the BRCA1-RBBP8 complex that regulates CHEK1
CC activation and controls cell cycle G2/M checkpoints on DNA damage.
CC Promotes microhomology-mediated alternative end joining (A-NHEJ)
CC during class-switch recombination and plays an essential role in
CC chromosomal translocations. {ECO:0000269|PubMed:10764811,
CC ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915,
CC ECO:0000269|PubMed:16581787, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191,
CC ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20064462,
CC ECO:0000269|PubMed:20829486}.
CC -!- SUBUNIT: Homodimer; dimerizes via the coiled coil domain.
CC Interacts (via the PXDLS motif) with CTBP1; the interaction is
CC disrupted via binding of the adenovirus E1A to CTBP1. Component of
CC the BRCA1-RBBBP8 complex. Interacts (the Ser-327 phosphorylated
CC form) with BRCA1 (via the C-terminal BRCA1 domains): the
CC interaction occurs in the G2 phase, ubiquitinates RBBP8 and
CC involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA
CC damage. Interacts with RB1. Interacts with the MRN complex.
CC Interacts directly with MRE11A; the interaction is required for
CC efficient homologous recombination (HR) and regulation of the MRN
CC complex. Interacts directly with RAD50. Interacts directly with
CC NBN. Interacts with SIRT6; the interaction deacetylates RBBP8 upon
CC DNA damage. Interacts with LM04 (via the LIM zinc-binding 1
CC domain). {ECO:0000269|PubMed:10764811,
CC ECO:0000269|PubMed:11751867, ECO:0000269|PubMed:14654780,
CC ECO:0000269|PubMed:15084581, ECO:0000269|PubMed:15485915,
CC ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17965729,
CC ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20829486,
CC ECO:0000269|PubMed:9535825, ECO:0000269|PubMed:9721205}.
CC -!- INTERACTION:
CC P38398:BRCA1; NbExp=9; IntAct=EBI-745715, EBI-349905;
CC Q9UQ84:EXO1; NbExp=3; IntAct=EBI-745715, EBI-944667;
CC P25800:LMO1; NbExp=3; IntAct=EBI-10203615, EBI-8639312;
CC P61968:LMO4; NbExp=3; IntAct=EBI-10203615, EBI-2798728;
CC Q13526:PIN1; NbExp=3; IntAct=EBI-10203615, EBI-714158;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10764811,
CC ECO:0000269|PubMed:17965729}. Note=Associates with sites of DNA
CC damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin
CC following DNA damage.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q99708-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99708-2; Sequence=VSP_043220;
CC Name=3;
CC IsoId=Q99708-3; Sequence=VSP_045247, VSP_045248;
CC Note=No experimental confirmation available. Ref.4 (BX648221)
CC sequence is in conflict in position: 862:S->G. {ECO:0000305};
CC -!- INDUCTION: Levels increase dramatically as dividing cells traverse
CC the G1/S boubdary. Down-regulated in tamoxifen-resistant breast
CC cancer cells.
CC -!- DOMAIN: The PXDLS motif binds to a cleft in CtBP proteins.
CC -!- DOMAIN: The damage-recruitment motif is required for DNA binding
CC and translocation to sites of DNA damage.
CC -!- PTM: Acetylated. Deacetylation by SIRT6 upon DNA damage promotes
CC DNA end resection. {ECO:0000269|PubMed:20829486}.
CC -!- PTM: Hyperphosphorylation upon ionizing radiation results in
CC dissociation from BRCA1. Phosphorylation at Thr-847 by CDK1 is
CC essential for the recruitment to DNA and the DNA repair function.
CC Phosphorylated on Ser-327 as cells enter G2 phase. This
CC phosphorylation is required for binding BRCA1 and for the G2/M DNA
CC damage transition checkpoint control.
CC {ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915,
CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191}.
CC -!- PTM: Ubiquitinated. Ubiquitination at multiple sites by BRCA1 (via
CC its N-terminal RING domain) does not lead to its proteosomal
CC degradation but instead the ubiquitinated RBBP8 binds to chromatin
CC following DNA damage and may play a role in G2/M checkpoint
CC control. {ECO:0000269|PubMed:14654780,
CC ECO:0000269|PubMed:16818604}.
CC -!- DISEASE: Seckel syndrome 2 (SCKL2) [MIM:606744]: A rare autosomal
CC recessive disorder characterized by proportionate dwarfism of
CC prenatal onset associated with low birth weight, growth
CC retardation, severe microcephaly with a bird-headed like
CC appearance, and mental retardation. {ECO:0000269|PubMed:21998596}.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- DISEASE: Jawad syndrome (JWDS) [MIM:251255]: A syndrome
CC characterized by congenital microcephaly, moderately severe mental
CC retardation, and symmetrical digital anomalies. Digital
CC malformations of variable degree include hallux valgus, syndactyly
CC of toes 4 and 5, short fifth fingers, single flexion crease of
CC fifth fingers, polydactyly and synpolydactyly.
CC {ECO:0000269|PubMed:21998596}. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- DISEASE: Note=Genetic variability in RBBP8 is noted as a factor in
CC BRCA1-associated breast cancer risk. Exhibits sensitivity to
CC tamoxifen in certain breast cancer cell lines.
CC -!- SIMILARITY: Belongs to the COM1/SAE2/CtIP family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RBBP8ID42066ch18q11.html";
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DR EMBL; AF043431; AAC34368.1; -; mRNA.
DR EMBL; U72066; AAC14371.1; -; mRNA.
DR EMBL; AK292481; BAF85170.1; -; mRNA.
DR EMBL; BX648221; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC091147; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC106033; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471088; EAX01144.1; -; Genomic_DNA.
DR EMBL; BC030590; AAH30590.1; -; mRNA.
DR CCDS; CCDS11874.1; -. [Q99708-3]
DR CCDS; CCDS11875.1; -. [Q99708-1]
DR RefSeq; NP_002885.1; NM_002894.2. [Q99708-1]
DR RefSeq; NP_976036.1; NM_203291.1. [Q99708-1]
DR RefSeq; NP_976037.1; NM_203292.1. [Q99708-3]
DR RefSeq; XP_006722582.1; XM_006722519.1. [Q99708-1]
DR RefSeq; XP_006722583.1; XM_006722520.1. [Q99708-1]
DR RefSeq; XP_006722584.1; XM_006722521.1. [Q99708-1]
DR RefSeq; XP_011524434.1; XM_011526132.1. [Q99708-1]
DR UniGene; Hs.546282; -.
DR PDB; 2L4Z; NMR; -; A=641-685.
DR PDB; 4D2H; X-ray; 1.90 A; A/B/C/D/E/F/G/H=18-52.
DR PDBsum; 2L4Z; -.
DR PDBsum; 4D2H; -.
DR ProteinModelPortal; Q99708; -.
DR SMR; Q99708; 18-52, 641-677.
DR BioGrid; 111867; 43.
DR DIP; DIP-24244N; -.
DR IntAct; Q99708; 27.
DR MINT; MINT-102295; -.
DR STRING; 9606.ENSP00000323050; -.
DR PhosphoSite; Q99708; -.
DR BioMuta; RBBP8; -.
DR DMDM; 116242745; -.
DR MaxQB; Q99708; -.
DR PaxDb; Q99708; -.
DR PRIDE; Q99708; -.
DR DNASU; 5932; -.
DR Ensembl; ENST00000327155; ENSP00000323050; ENSG00000101773. [Q99708-1]
DR Ensembl; ENST00000399722; ENSP00000382628; ENSG00000101773. [Q99708-1]
DR Ensembl; ENST00000399725; ENSP00000382630; ENSG00000101773. [Q99708-3]
DR GeneID; 5932; -.
DR KEGG; hsa:5932; -.
DR UCSC; uc002ktw.3; human. [Q99708-1]
DR UCSC; uc002ktz.3; human.
DR CTD; 5932; -.
DR GeneCards; RBBP8; -.
DR GeneReviews; RBBP8; -.
DR HGNC; HGNC:9891; RBBP8.
DR HPA; HPA039890; -.
DR HPA; HPA052946; -.
DR MIM; 251255; phenotype.
DR MIM; 604124; gene.
DR MIM; 606744; phenotype.
DR neXtProt; NX_Q99708; -.
DR Orphanet; 313795; Jawad syndrome.
DR Orphanet; 808; Seckel syndrome.
DR PharmGKB; PA34255; -.
DR eggNOG; ENOG410IJ39; Eukaryota.
DR eggNOG; ENOG410ZSBE; LUCA.
DR GeneTree; ENSGT00530000063835; -.
DR HOGENOM; HOG000293331; -.
DR HOVERGEN; HBG057046; -.
DR InParanoid; Q99708; -.
DR OrthoDB; EOG771274; -.
DR PhylomeDB; Q99708; -.
DR TreeFam; TF106469; -.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR ChiTaRS; RBBP8; human.
DR EvolutionaryTrace; Q99708; -.
DR GeneWiki; RBBP8; -.
DR GenomeRNAi; 5932; -.
DR NextBio; 23118; -.
DR PRO; PR:Q99708; -.
DR Proteomes; UP000005640; Chromosome 18.
DR Bgee; Q99708; -.
DR CleanEx; HS_RBBP8; -.
DR ExpressionAtlas; Q99708; baseline and differential.
DR Genevisible; Q99708; HS.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0017053; C:transcriptional repressor complex; IDA:BHF-UCL.
DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IMP:UniProtKB.
DR GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl.
DR GO; GO:0000075; P:cell cycle checkpoint; TAS:ProtInc.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0010792; P:DNA double-strand break processing involved in repair via single-strand annealing; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0031572; P:G2 DNA damage checkpoint; IDA:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007067; P:mitotic nuclear division; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:GOC.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:CACAO.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR InterPro; IPR013882; Com1/Ctip_fam.
DR InterPro; IPR019518; CtIP_N.
DR Pfam; PF10482; CtIP_N; 1.
DR Pfam; PF08573; SAE2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell cycle;
KW Cell division; Coiled coil; Complete proteome; DNA damage; DNA repair;
KW DNA-binding; Dwarfism; Endonuclease; Hydrolase; Isopeptide bond;
KW Meiosis; Mental retardation; Mitosis; Nuclease; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation.
FT CHAIN 1 897 DNA endonuclease RBBP8.
FT /FTId=PRO_0000097179.
FT REGION 22 45 Essential for binding to the MRN complex
FT and for RPA focus formation on DNA
FT damage.
FT REGION 509 557 Damage-recruitment motif.
FT COILED 28 157 {ECO:0000255}.
FT MOTIF 490 494 PXDLS motif.
FT COMPBIAS 750 753 Poly-Glu.
FT MOD_RES 233 233 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q80YR6}.
FT MOD_RES 326 326 Phosphoserine.
FT {ECO:0000269|PubMed:17965729}.
FT MOD_RES 327 327 Phosphoserine.
FT {ECO:0000269|PubMed:15485915}.
FT MOD_RES 349 349 Phosphoserine.
FT {ECO:0000269|PubMed:17965729}.
FT MOD_RES 432 432 N6-acetyllysine.
FT {ECO:0000269|PubMed:20829486}.
FT MOD_RES 526 526 N6-acetyllysine.
FT {ECO:0000269|PubMed:20829486}.
FT MOD_RES 604 604 N6-acetyllysine.
FT {ECO:0000269|PubMed:20829486}.
FT MOD_RES 664 664 Phosphoserine; by ATM.
FT {ECO:0000269|PubMed:10910365}.
FT MOD_RES 679 679 Phosphoserine.
FT {ECO:0000269|PubMed:17965729}.
FT MOD_RES 723 723 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 745 745 Phosphoserine; by ATM.
FT {ECO:0000269|PubMed:10910365}.
FT MOD_RES 847 847 Phosphothreonine; by CDK1.
FT {ECO:0000269|PubMed:19202191}.
FT CROSSLNK 869 869 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT VAR_SEQ 714 714 S -> SMLFYI (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_043220.
FT VAR_SEQ 786 867 RETSLQNFPHIEVVRKKEERRKLLGHTCKECEIYYADMPAE
FT EREKKLASCSRHRFRYIPPNTPENFWEVGFPSTQTCMERGY
FT -> SIMQICQQKKEKRNWLPAQDTDSATFHPTHQRIFGKLV
FT FLPLRLVWKEVILRKILILVLVQKDVSLTTQYFLQKARSRR
FT HRR (in isoform 3).
FT {ECO:0000303|PubMed:17974005}.
FT /FTId=VSP_045247.
FT VAR_SEQ 868 897 Missing (in isoform 3).
FT {ECO:0000303|PubMed:17974005}.
FT /FTId=VSP_045248.
FT VARIANT 357 357 K -> N (in dbSNP:rs34678569).
FT /FTId=VAR_051308.
FT VARIANT 387 387 H -> Y (in dbSNP:rs1804732).
FT /FTId=VAR_028308.
FT MUTAGEN 31 31 H->A: No effect on RPA focus formation on
FT DNA damage.
FT {ECO:0000269|PubMed:19759395}.
FT MUTAGEN 35 35 V->A: No effect on RPA focus formation on
FT DNA damage.
FT {ECO:0000269|PubMed:19759395}.
FT MUTAGEN 41 41 K->A: No effect on RPA focus formation on
FT DNA damage.
FT {ECO:0000269|PubMed:19759395}.
FT MUTAGEN 45 45 L->A: No effect on RPA focus formation on
FT DNA damage.
FT {ECO:0000269|PubMed:19759395}.
FT MUTAGEN 327 327 S->A: Abolishes BRCA1 interaction and
FT ubiquitination. No activation of CHEK1
FT after DNA damage.
FT {ECO:0000269|PubMed:15485915,
FT ECO:0000269|PubMed:16818604}.
FT MUTAGEN 432 432 K->R: Greatly reduced acetylation.
FT Alleviates resection defects caused by
FT depletion of SIRT6; when associated with
FT R-526 and R-604.
FT {ECO:0000269|PubMed:20829486}.
FT MUTAGEN 513 513 K->A: Abolishes damage recruitment
FT capability.
FT {ECO:0000269|PubMed:20064462}.
FT MUTAGEN 515 515 K->A: Abolishes damage recruitment
FT capability.
FT {ECO:0000269|PubMed:20064462}.
FT MUTAGEN 526 526 K->R: Greatly reduced acetylation.
FT Alleviates resection defects caused by
FT depletion of SIRT6; when associated with
FT R-432 and R-604.
FT {ECO:0000269|PubMed:20829486}.
FT MUTAGEN 604 604 K->R: Greatly reduced acetylation.
FT Alleviates resection defects caused by
FT depletion of SIRT6; when associated with
FT R-432 and R-526.
FT {ECO:0000269|PubMed:20829486}.
FT MUTAGEN 664 664 S->A: Abrogates dissociation of BRCA1.
FT {ECO:0000269|PubMed:10910365}.
FT MUTAGEN 745 745 S->A: Abrogates dissociation of BRCA1.
FT {ECO:0000269|PubMed:10910365}.
FT MUTAGEN 847 847 T->A: Impairs DNA resection.
FT {ECO:0000269|PubMed:19202191}.
FT MUTAGEN 847 847 T->E: Mimics constitutive
FT phosphorylation.
FT {ECO:0000269|PubMed:19202191}.
FT CONFLICT 4 4 S -> L (in Ref. 1; AAC14371).
FT {ECO:0000305}.
FT CONFLICT 74 74 H -> Q (in Ref. 4; BX648221).
FT {ECO:0000305}.
FT CONFLICT 92 92 C -> Y (in Ref. 3; BAF85170).
FT {ECO:0000305}.
FT CONFLICT 123 123 E -> G (in Ref. 3; BAF85170).
FT {ECO:0000305}.
FT CONFLICT 341 341 D -> G (in Ref. 4; BX648221).
FT {ECO:0000305}.
FT CONFLICT 515 515 K -> R (in Ref. 4; BX648221).
FT {ECO:0000305}.
FT CONFLICT 521 521 L -> P (in Ref. 3; BAF85170).
FT {ECO:0000305}.
FT CONFLICT 642 642 L -> P (in Ref. 4; BX648221).
FT {ECO:0000305}.
FT HELIX 18 50 {ECO:0000244|PDB:4D2H}.
FT STRAND 648 650 {ECO:0000244|PDB:2L4Z}.
FT HELIX 651 653 {ECO:0000244|PDB:2L4Z}.
FT TURN 662 666 {ECO:0000244|PDB:2L4Z}.
FT STRAND 677 679 {ECO:0000244|PDB:2L4Z}.
SQ SEQUENCE 897 AA; 101942 MW; E028DE56DE55C0F2 CRC64;
MNISGSSCGS PNSADTSSDF KDLWTKLKEC HDREVQGLQV KVTKLKQERI LDAQRLEEFF
TKNQQLREQQ KVLHETIKVL EDRLRAGLCD RCAVTEEHMR KKQQEFENIR QQNLKLITEL
MNERNTLQEE NKKLSEQLQQ KIENDQQHQA AELECEEDVI PDSPITAFSF SGVNRLRRKE
NPHVRYIEQT HTKLEHSVCA NEMRKVSKSS THPQHNPNEN EILVADTYDQ SQSPMAKAHG
TSSYTPDKSS FNLATVVAET LGLGVQEESE TQGPMSPLGD ELYHCLEGNH KKQPFEESTR
NTEDSLRFSD STSKTPPQEE LPTRVSSPVF GATSSIKSGL DLNTSLSPSL LQPGKKKHLK
TLPFSNTCIS RLEKTRSKSE DSALFTHHSL GSEVNKIIIQ SSNKQILINK NISESLGEQN
RTEYGKDSNT DKHLEPLKSL GGRTSKRKKT EEESEHEVSC PQASFDKENA FPFPMDNQFS
MNGDCVMDKP LDLSDRFSAI QRQEKSQGSE TSKNKFRQVT LYEALKTIPK GFSSSRKASD
GNCTLPKDSP GEPCSQECII LQPLNKCSPD NKPSLQIKEE NAVFKIPLRP RESLETENVL
DDIKSAGSHE PIKIQTRSDH GGCELASVLQ LNPCRTGKIK SLQNNQDVSF ENIQWSIDPG
ADLSQYKMDV TVIDTKDGSQ SKLGGETVDM DCTLVSETVL LKMKKQEQKG EKSSNEERKM
NDSLEDMFDR TTHEEYESCL ADSFSQAADE EEELSTATKK LHTHGDKQDK VKQKAFVEPY
FKGDERETSL QNFPHIEVVR KKEERRKLLG HTCKECEIYY ADMPAEEREK KLASCSRHRF
RYIPPNTPEN FWEVGFPSTQ TCMERGYIKE DLDPCPRPKR RQPYNAIFSP KGKEQKT
//
ID CTBP1_HUMAN Reviewed; 440 AA.
AC Q13363; Q4W5N3; Q7Z2Q5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 11-NOV-2015, entry version 173.
DE RecName: Full=C-terminal-binding protein 1;
DE Short=CtBP1;
DE EC=1.1.1.-;
GN Name=CTBP1; Synonyms=CTBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 98-108,
RP AND INTERACTION WITH RBBP8 AND ADENOVIRUS E1A.
RC TISSUE=B-cell, and Cervix carcinoma;
RX PubMed=7479821; DOI=10.1073/pnas.92.23.10467;
RA Schaeper U., Boyd J.M., Verma S., Uhlmann E., Subramanian T.,
RA Chinnadurai G.;
RT "Molecular cloning and characterization of a cellular phosphoprotein
RT that interacts with a conserved C-terminal domain of adenovirus E1A
RT involved in negative modulation of oncogenic transformation.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10467-10471(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SEQUENCE REVISION, AND
RP FUNCTION.
RX PubMed=9858600;
RA Sewalt R.G.A.B., Gunster M.J., van der Vlag J., Satijn D.P.E.,
RA Otte A.P.;
RT "C-terminal binding protein is a transcriptional repressor that
RT interacts with a specific class of vertebrate polycomb proteins.";
RL Mol. Cell. Biol. 19:777-787(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH ADENOVIRUS E1A, AND PHOSPHORYLATION.
RX PubMed=8440238;
RA Boyd J.M., Subramanian T., Schaeper U., la Regina M., Bayley S.,
RA Chinnadurai G.;
RT "A region in the C-terminus of adenovirus 2/5 E1a protein is required
RT for association with a cellular phosphoprotein and important for the
RT negative modulation of T24-ras mediated transformation, tumorigenesis
RT and metastasis.";
RL EMBO J. 12:469-478(1993).
RN [7]
RP INTERACTION WITH MECOM.
RX PubMed=11568182; DOI=10.1074/jbc.M106733200;
RA Chakraborty S., Senyuk V., Sitailo S., Chi Y., Nucifora G.;
RT "Interaction of EVI1 with cAMP-responsive element-binding protein-
RT binding protein (CBP) and p300/CBP-associated factor (P/CAF) results
RT in reversible acetylation of EVI1 and in co-localization in nuclear
RT speckles.";
RL J. Biol. Chem. 276:44936-44943(2001).
RN [8]
RP INTERACTION WITH EBV EBNA6.
RX PubMed=11462050; DOI=10.1128/JVI.75.16.7749-7755.2001;
RA Touitou R., Hickabottom M., Parker G., Crook T., Allday M.J.;
RT "Physical and functional interactions between the corepressor CtBP and
RT the Epstein-Barr virus nuclear antigen EBNA3C.";
RL J. Virol. 75:7749-7755(2001).
RN [9]
RP INTERACTION WITH NRIP1.
RX PubMed=11509661; DOI=10.1128/MCB.21.18.6181-6188.2001;
RA Vo N., Fjeld C., Goodman R.H.;
RT "Acetylation of nuclear hormone receptor-interacting protein RIP140
RT regulates binding of the transcriptional corepressor CtBP.";
RL Mol. Cell. Biol. 21:6181-6188(2001).
RN [10]
RP INTERACTION WITH EBV EBNA3.
RX PubMed=12372828; DOI=10.1074/jbc.M208116200;
RA Hickabottom M., Parker G.A., Freemont P., Crook T., Allday M.J.;
RT "Two nonconsensus sites in the Epstein-Barr virus oncoprotein EBNA3A
RT cooperate to bind the co-repressor carboxyl-terminal-binding protein
RT (CtBP).";
RL J. Biol. Chem. 277:47197-47204(2002).
RN [11]
RP SUMOYLATION AT LYS-428, AND SUBCELLULAR LOCATION.
RX PubMed=12679040; DOI=10.1016/S0092-8674(03)00159-4;
RA Kagey M.H., Melhuish T.A., Wotton D.;
RT "The polycomb protein Pc2 is a SUMO E3.";
RL Cell 113:127-137(2003).
RN [12]
RP INTERACTION WITH HIPK2, PHOSPHORYLATION AT SER-422, AND MUTAGENESIS OF
RP SER-422.
RX PubMed=14567915; DOI=10.1016/S0092-8674(03)00802-X;
RA Zhang Q., Yoshimatsu Y., Hildebrand J., Frisch S.M., Goodman R.H.;
RT "Homeodomain interacting protein kinase 2 promotes apoptosis by
RT downregulating the transcriptional corepressor CtBP.";
RL Cell 115:177-186(2003).
RN [13]
RP FUNCTION IN TRANSCRIPTIONAL REPRESSION, AND INTERACTION WITH PNN.
RX PubMed=15542832; DOI=10.1128/MCB.24.23.10223-10235.2004;
RA Alpatov R., Munguba G.C., Caton P., Joo J.H., Shi Y., Shi Y.,
RA Hunt M.E., Sugrue S.P.;
RT "Nuclear speckle-associated protein Pnn/DRS binds to the
RT transcriptional corepressor CtBP and relieves CtBP-mediated repression
RT of the E-cadherin gene.";
RL Mol. Cell. Biol. 24:10223-10235(2004).
RN [14]
RP INTERACTION WITH NRIP1.
RX PubMed=15060175; DOI=10.1093/nar/gkh524;
RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P.,
RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.;
RT "Multiple domains of the receptor-interacting protein 140 contribute
RT to transcription inhibition.";
RL Nucleic Acids Res. 32:1957-1966(2004).
RN [15]
RP INTERACTION WITH ZFHX1B.
RX PubMed=16061479; DOI=10.1074/jbc.M504477200;
RA Long J., Zuo D., Park M.;
RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates
RT transcriptional repression of E-cadherin.";
RL J. Biol. Chem. 280:35477-35489(2005).
RN [16]
RP INTERACTION WITH MECOM.
RX PubMed=15897867; DOI=10.1038/sj.onc.1208754;
RA Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S.,
RA Kurokawa M., Hirai H.;
RT "Oligomerization of Evi-1 regulated by the PR domain contributes to
RT recruitment of corepressor CtBP.";
RL Oncogene 24:6165-6173(2005).
RN [17]
RP INTERACTION WITH FOXP1.
RX PubMed=16609867; DOI=10.1007/s00427-006-0073-8;
RA Schoen C., Wochnik A., Roessner A., Donow C., Knoechel W.;
RT "The FoxP subclass in Xenopus laevis development.";
RL Dev. Genes Evol. 216:641-646(2006).
RN [18]
RP INTERACTION WITH WIZ.
RX PubMed=16702210; DOI=10.1074/jbc.M603087200;
RA Ueda J., Tachibana M., Ikura T., Shinkai Y.;
RT "Zinc finger protein Wiz links G9a/GLP histone methyltransferases to
RT the co-repressor molecule CtBP.";
RL J. Biol. Chem. 281:20120-20128(2006).
RN [19]
RP INTERACTION WITH ZNF366.
RX PubMed=17085477; DOI=10.1093/nar/gkl875;
RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M.,
RA Jat P., Kindle K.B., Heery D.M., Parker M.G., Buluwela L.,
RA Kamalati T., Ali S.;
RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and
RT histone deacetylases.";
RL Nucleic Acids Res. 34:6126-6136(2006).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-300, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [21]
RP FUNCTION AS COREPRESSOR, INTERACTION WITH BCL6, AND TISSUE
RP SPECIFICITY.
RX PubMed=18212045; DOI=10.1128/MCB.01400-07;
RA Mendez L.M., Polo J.M., Yu J.J., Krupski M., Ding B.B., Melnick A.,
RA Ye B.H.;
RT "CtBP is an essential corepressor for BCL6 autoregulation.";
RL Mol. Cell. Biol. 28:2175-2186(2008).
RN [22]
RP FUNCTION, AND INTERACTION WITH SATB1.
RX PubMed=19103759; DOI=10.1128/MCB.00822-08;
RA Purbey P.K., Singh S., Notani D., Kumar P.P., Limaye A.S., Galande S.;
RT "Acetylation-dependent interaction of SATB1 and CtBP1 mediates
RT transcriptional repression by SATB1.";
RL Mol. Cell. Biol. 29:1321-1337(2009).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP INTERACTION WITH HADV5 E1A.
RX PubMed=23747199; DOI=10.1016/j.virol.2013.05.018;
RA Subramanian T., Zhao L.J., Chinnadurai G.;
RT "Interaction of CtBP with adenovirus E1A suppresses immortalization of
RT primary epithelial cells and enhances virus replication during
RT productive infection.";
RL Virology 443:313-320(2013).
RN [25]
RP INTERACTION WITH FAM195B.
RX PubMed=25728771; DOI=10.1016/j.molcel.2015.01.023;
RA Ichikawa K., Kubota Y., Nakamura T., Weng J.S., Tomida T., Saito H.,
RA Takekawa M.;
RT "MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during
RT epithelial-mesenchymal transition by regulating the co-repressor
RT CtBP.";
RL Mol. Cell 58:35-46(2015).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 28-353 IN COMPLEX WITH NAD,
RP FUNCTION, COFACTOR, MUTAGENESIS OF CYS-134; ASN-138; ARG-141;
RP 141-ARG-ARG-142; LEU-150; ARG-163; ARG-171; GLY-181; GLY-183; ASP-204;
RP ARG-266; ASP-290; GLU-295 AND HIS-315, AND DIMERIZATION.
RX PubMed=12419229; DOI=10.1016/S1097-2765(02)00650-0;
RA Kumar V., Carlson J.E., Ohgi K.A., Edwards T.A., Rose D.W.,
RA Escalante C.R., Rosenfeld M.G., Aggarwal A.K.;
RT "Transcription corepressor CtBP is an NAD(+)-regulated
RT dehydrogenase.";
RL Mol. Cell 10:857-869(2002).
CC -!- FUNCTION: Corepressor targeting diverse transcription regulators
CC such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in
CC controlling the equilibrium between tubular and stacked structures
CC in the Golgi complex. Functions in brown adipose tissue (BAT)
CC differentiation. {ECO:0000269|PubMed:12419229,
CC ECO:0000269|PubMed:15542832, ECO:0000269|PubMed:18212045,
CC ECO:0000269|PubMed:19103759, ECO:0000269|PubMed:9858600}.
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000269|PubMed:12419229};
CC Note=NAD is required for efficient interaction with E1A. Cofactor
CC binding induces a conformation change.
CC {ECO:0000269|PubMed:12419229};
CC -!- SUBUNIT: Homo- or heterodimer. Heterodimer with CTBP2. Interacts
CC with PRDM16; the interaction represses white adipose tissue (WAT)-
CC specific genes expression. Interacts with GLIS2, FOXP2, HDAC4,
CC HDAC5, HDAC9 and ZNF217. Interacts with adenovirus E1A protein
CC (via its C-terminus); the interaction disrupts the interaction of
CC CTBP1 with RBBP8. Interacts with Epstein-Barr virus EBNA3 and
CC EBNA6. Interacts with ELK3 (via its PXDLS motif). Interacts with
CC RBBP8 (via its PXDLS motif); the interaction is disrupted by
CC binding to adenovirus E1A. Interacts with FOXP1, HIPK2, PNN,
CC NRIP1, MECOM, ZNF366, ZFHX1B and WIZ. Interaction with SATB1 (non-
CC acetylated form); the interaction stabilizes its attachment to DNA
CC and promotes transcription repression. Interacts with BCL6; the
CC interaction is required for BCL6 transcriptional autoinhibition
CC and inhibition of some BCL6 target genes. Interacts with IKZF4 (By
CC similarity). Interacts with human adenovirus 5 E1A protein; this
CC interaction seems to potentiate viral replication
CC (PubMed:23747199). Interacts with FAM195B (unphosphorylated form,
CC via the PXDLS motif); competitively inhibiting CTBP-ZEB1
CC interaction (PubMed:25728771). {ECO:0000250|UniProtKB:O88712,
CC ECO:0000269|PubMed:11462050, ECO:0000269|PubMed:11509661,
CC ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:12372828,
CC ECO:0000269|PubMed:12419229, ECO:0000269|PubMed:14567915,
CC ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:15542832,
CC ECO:0000269|PubMed:15897867, ECO:0000269|PubMed:16061479,
CC ECO:0000269|PubMed:16609867, ECO:0000269|PubMed:16702210,
CC ECO:0000269|PubMed:17085477, ECO:0000269|PubMed:18212045,
CC ECO:0000269|PubMed:19103759, ECO:0000269|PubMed:23747199,
CC ECO:0000269|PubMed:25728771, ECO:0000269|PubMed:7479821,
CC ECO:0000269|PubMed:8440238}.
CC -!- INTERACTION:
CC Q9H6U6:BCAS3; NbExp=3; IntAct=EBI-10171858, EBI-6083685;
CC Q76N32:CEP68; NbExp=3; IntAct=EBI-10171858, EBI-9051024;
CC Q49AN0:CRY2; NbExp=3; IntAct=EBI-10171858, EBI-2212355;
CC P56545:CTBP2; NbExp=3; IntAct=EBI-10171858, EBI-741533;
CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-10171858, EBI-10171902;
CC I6L9A0:DMRTB1; NbExp=3; IntAct=EBI-10171858, EBI-10178554;
CC O15409:FOXP2; NbExp=3; IntAct=EBI-10171858, EBI-983612;
CC Q9BXL5:HEMGN; NbExp=2; IntAct=EBI-908846, EBI-3916399;
CC Q14526:HIC1; NbExp=4; IntAct=EBI-908846, EBI-2507362;
CC P09067:HOXB5; NbExp=3; IntAct=EBI-10171858, EBI-3893317;
CC Q13422:IKZF1; NbExp=3; IntAct=EBI-10171858, EBI-745305;
CC Q9Y4X4:KLF12; NbExp=3; IntAct=EBI-10171858, EBI-750750;
CC O43474:KLF4; NbExp=4; IntAct=EBI-908846, EBI-7232405;
CC P45984:MAPK9; NbExp=3; IntAct=EBI-10171858, EBI-713568;
CC O94818-2:NOL4; NbExp=3; IntAct=EBI-10171858, EBI-10190763;
CC Q96MY1:NOL4L; NbExp=3; IntAct=EBI-10171858, EBI-6660790;
CC Q9NQ66:PLCB1; NbExp=3; IntAct=EBI-10171858, EBI-3396023;
CC Q13131:PRKAA1; NbExp=3; IntAct=EBI-10171858, EBI-1181405;
CC Q15583:TGIF1; NbExp=3; IntAct=EBI-10171858, EBI-714215;
CC Q96EK4:THAP11; NbExp=2; IntAct=EBI-908846, EBI-1790529;
CC A1L0U7:TSHZ3; NbExp=3; IntAct=EBI-10171858, EBI-10171826;
CC A2APF7:Zbp1 (xeno); NbExp=2; IntAct=EBI-908846, EBI-6115394;
CC Q8N895:ZNF366; NbExp=5; IntAct=EBI-908846, EBI-2813661;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12679040}.
CC Nucleus {ECO:0000269|PubMed:12679040}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13363-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13363-2; Sequence=VSP_043305;
CC Note=No experimental confirmation available.;
CC -!- TISSUE SPECIFICITY: Expressed in germinal center B-cells.
CC {ECO:0000269|PubMed:18212045}.
CC -!- PTM: The level of phosphorylation appears to be regulated during
CC the cell cycle. Phosphorylation by HIPK2 on Ser-422 induces
CC proteasomal degradation. {ECO:0000269|PubMed:14567915,
CC ECO:0000269|PubMed:8440238}.
CC -!- PTM: ADP-ribosylated; when cells are exposed to brefeldin A.
CC {ECO:0000250}.
CC -!- PTM: Sumoylation on Lys-428 is promoted by the E3 SUMO-protein
CC ligase CBX4. {ECO:0000269|PubMed:12679040}.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; U37408; AAC62822.1; -; mRNA.
DR EMBL; AF091555; AAD14597.1; -; mRNA.
DR EMBL; AC092535; AAY40989.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82599.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82600.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82601.1; -; Genomic_DNA.
DR EMBL; BC011655; AAH11655.1; -; mRNA.
DR EMBL; BC053320; AAH53320.1; -; mRNA.
DR CCDS; CCDS3348.1; -. [Q13363-1]
DR CCDS; CCDS43203.1; -. [Q13363-2]
DR RefSeq; NP_001012632.1; NM_001012614.1. [Q13363-2]
DR RefSeq; NP_001319.1; NM_001328.2. [Q13363-1]
DR UniGene; Hs.208597; -.
DR PDB; 1MX3; X-ray; 1.95 A; A=28-353.
DR PDB; 4LCE; X-ray; 2.38 A; A=28-353.
DR PDB; 4U6Q; X-ray; 2.30 A; A=28-353.
DR PDB; 4U6S; X-ray; 2.10 A; A=28-353.
DR PDBsum; 1MX3; -.
DR PDBsum; 4LCE; -.
DR PDBsum; 4U6Q; -.
DR PDBsum; 4U6S; -.
DR ProteinModelPortal; Q13363; -.
DR SMR; Q13363; 28-352.
DR BioGrid; 107869; 137.
DR DIP; DIP-24245N; -.
DR IntAct; Q13363; 40.
DR MINT; MINT-94454; -.
DR STRING; 9606.ENSP00000290921; -.
DR PhosphoSite; Q13363; -.
DR BioMuta; CTBP1; -.
DR DMDM; 6014741; -.
DR MaxQB; Q13363; -.
DR PaxDb; Q13363; -.
DR PRIDE; Q13363; -.
DR DNASU; 1487; -.
DR Ensembl; ENST00000290921; ENSP00000290921; ENSG00000159692. [Q13363-1]
DR Ensembl; ENST00000382952; ENSP00000372411; ENSG00000159692. [Q13363-2]
DR GeneID; 1487; -.
DR KEGG; hsa:1487; -.
DR UCSC; uc003gcu.1; human. [Q13363-2]
DR UCSC; uc003gcv.1; human. [Q13363-1]
DR CTD; 1487; -.
DR GeneCards; CTBP1; -.
DR HGNC; HGNC:2494; CTBP1.
DR HPA; CAB004217; -.
DR HPA; HPA018987; -.
DR HPA; HPA044971; -.
DR MIM; 602618; gene.
DR neXtProt; NX_Q13363; -.
DR PharmGKB; PA26995; -.
DR eggNOG; KOG0067; Eukaryota.
DR eggNOG; COG0111; LUCA.
DR GeneTree; ENSGT00530000063021; -.
DR HOGENOM; HOG000136701; -.
DR HOVERGEN; HBG001898; -.
DR InParanoid; Q13363; -.
DR KO; K04496; -.
DR OMA; DRDHPSD; -.
DR OrthoDB; EOG761BT9; -.
DR PhylomeDB; Q13363; -.
DR TreeFam; TF313593; -.
DR Reactome; R-HSA-3769402; deactivation of the beta-catenin transactivating complex.
DR Reactome; R-HSA-4641265; repression of WNT target genes.
DR Reactome; R-HSA-5339700; TCF7L2 mutants don't bind CTBP.
DR SignaLink; Q13363; -.
DR ChiTaRS; CTBP1; human.
DR EvolutionaryTrace; Q13363; -.
DR GeneWiki; CTBP1; -.
DR GenomeRNAi; 1487; -.
DR NextBio; 6105; -.
DR PRO; PR:Q13363; -.
DR Proteomes; UP000005640; Chromosome 4.
DR Bgee; Q13363; -.
DR CleanEx; HS_CTBP1; -.
DR ExpressionAtlas; Q13363; baseline and differential.
DR Genevisible; Q13363; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl.
DR GO; GO:0017053; C:transcriptional repressor complex; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; ISS:UniProtKB.
DR GO; GO:0070404; F:NADH binding; IBA:GO_Central.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; TAS:ProtInc.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0070491; F:repressing transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0035067; P:negative regulation of histone acetylation; IMP:BHF-UCL.
DR GO; GO:0090241; P:negative regulation of histone H4 acetylation; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:1903758; P:negative regulation of transcription from RNA polymerase II promoter by histone modification; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR GO; GO:0019079; P:viral genome replication; TAS:ProtInc.
DR GO; GO:0050872; P:white fat cell differentiation; ISS:UniProtKB.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR029753; D-isomer_DH_CS.
DR InterPro; IPR029752; D-isomer_DH_CS1.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Alternative splicing;
KW Complete proteome; Cytoplasm; Differentiation;
KW Direct protein sequencing; Host-virus interaction; Isopeptide bond;
KW NAD; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1 440 C-terminal-binding protein 1.
FT /FTId=PRO_0000076041.
FT NP_BIND 180 185 NAD. {ECO:0000250}.
FT NP_BIND 237 243 NAD. {ECO:0000250}.
FT NP_BIND 264 266 NAD. {ECO:0000250}.
FT NP_BIND 315 318 NAD. {ECO:0000250}.
FT REGION 1 70 Interaction with GLIS2 1. {ECO:0000250}.
FT REGION 288 360 Interaction with GLIS2 2. {ECO:0000250}.
FT ACT_SITE 266 266 {ECO:0000250}.
FT ACT_SITE 295 295 {ECO:0000250}.
FT ACT_SITE 315 315 Proton donor. {ECO:0000250}.
FT BINDING 100 100 NAD. {ECO:0000250}.
FT BINDING 204 204 NAD. {ECO:0000250}.
FT BINDING 290 290 NAD. {ECO:0000250}.
FT MOD_RES 300 300 Phosphoserine.
FT {ECO:0000244|PubMed:17525332}.
FT MOD_RES 422 422 Phosphoserine; by HIPK2.
FT {ECO:0000269|PubMed:14567915}.
FT CROSSLNK 428 428 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT VAR_SEQ 1 13 MGSSHLLNKGLPL -> MS (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_043305.
FT MUTAGEN 134 134 C->A: Strongly reduces E1A binding; when
FT associated with A-138; A-141 and A-150.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 138 138 N->A: Strongly reduces E1A binding; when
FT associated with A-134; A-141 and A-150.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 141 142 RR->AA: Strongly reduces E1A binding;
FT when associated with A-163 and A-171.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 141 141 R->A: Strongly reduces E1A binding; when
FT associated with A-134; A-138 and A-150.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 150 150 L->A: Strongly reduces E1A binding; when
FT associated with A-134; A-138 and A-141.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 163 163 R->A: Strongly reduces E1A binding; when
FT associated with A-141; A-142 and A-171.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 171 171 R->A: Strongly reduces E1A binding; when
FT associated with A-141; A-142 and A-163.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 181 181 G->V: Strongly reduces E1A binding; when
FT associated with V-183 and A-204.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 183 183 G->V: Strongly reduces E1A binding; when
FT associated with V-181 and A-204.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 204 204 D->A: Strongly reduces E1A binding; when
FT associated with V-181 and V-183.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 266 266 R->A: Strongly reduces E1A binding; when
FT associated with A-290; A-295 and A-315.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 290 290 D->A: Strongly reduces E1A binding; when
FT associated with A-266; A-295 and A-315.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 295 295 E->A: Strongly reduces E1A binding; when
FT associated with A-266; A-290 and A-315.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 315 315 H->A: Strongly reduces E1A binding; when
FT associated with A-266; A-290 and A-295.
FT {ECO:0000269|PubMed:12419229}.
FT MUTAGEN 422 422 S->A: Abolishes phosphorylation by HIPK2
FT and prevents UV-induced clearance.
FT {ECO:0000269|PubMed:14567915}.
FT STRAND 29 34 {ECO:0000244|PDB:1MX3}.
FT TURN 39 41 {ECO:0000244|PDB:1MX3}.
FT HELIX 42 45 {ECO:0000244|PDB:1MX3}.
FT TURN 46 48 {ECO:0000244|PDB:1MX3}.
FT STRAND 50 53 {ECO:0000244|PDB:1MX3}.
FT HELIX 59 61 {ECO:0000244|PDB:1MX3}.
FT HELIX 64 69 {ECO:0000244|PDB:1MX3}.
FT STRAND 70 75 {ECO:0000244|PDB:1MX3}.
FT STRAND 77 79 {ECO:0000244|PDB:1MX3}.
FT HELIX 83 86 {ECO:0000244|PDB:1MX3}.
FT STRAND 94 100 {ECO:0000244|PDB:1MX3}.
FT HELIX 107 112 {ECO:0000244|PDB:1MX3}.
FT STRAND 116 118 {ECO:0000244|PDB:1MX3}.
FT TURN 121 124 {ECO:0000244|PDB:4U6S}.
FT HELIX 125 141 {ECO:0000244|PDB:1MX3}.
FT HELIX 143 151 {ECO:0000244|PDB:1MX3}.
FT HELIX 159 165 {ECO:0000244|PDB:1MX3}.
FT TURN 166 168 {ECO:0000244|PDB:1MX3}.
FT STRAND 176 180 {ECO:0000244|PDB:1MX3}.
FT HELIX 184 194 {ECO:0000244|PDB:1MX3}.
FT TURN 195 197 {ECO:0000244|PDB:1MX3}.
FT STRAND 199 203 {ECO:0000244|PDB:1MX3}.
FT HELIX 211 215 {ECO:0000244|PDB:1MX3}.
FT HELIX 223 229 {ECO:0000244|PDB:1MX3}.
FT STRAND 231 235 {ECO:0000244|PDB:1MX3}.
FT STRAND 246 248 {ECO:0000244|PDB:1MX3}.
FT HELIX 249 252 {ECO:0000244|PDB:1MX3}.
FT STRAND 259 263 {ECO:0000244|PDB:1MX3}.
FT HELIX 267 269 {ECO:0000244|PDB:4U6S}.
FT HELIX 272 280 {ECO:0000244|PDB:1MX3}.
FT STRAND 283 290 {ECO:0000244|PDB:1MX3}.
FT STRAND 293 296 {ECO:0000244|PDB:1MX3}.
FT TURN 303 306 {ECO:0000244|PDB:1MX3}.
FT STRAND 308 312 {ECO:0000244|PDB:1MX3}.
FT HELIX 321 340 {ECO:0000244|PDB:1MX3}.
FT TURN 343 346 {ECO:0000244|PDB:1MX3}.
FT STRAND 348 350 {ECO:0000244|PDB:1MX3}.
SQ SEQUENCE 440 AA; 47535 MW; F071DD30B385603F CRC64;
MGSSHLLNKG LPLGVRPPIM NGPLHPRPLV ALLDGRDCTV EMPILKDVAT VAFCDAQSTQ
EIHEKVLNEA VGALMYHTIT LTREDLEKFK ALRIIVRIGS GFDNIDIKSA GDLGIAVCNV
PAASVEETAD STLCHILNLY RRATWLHQAL REGTRVQSVE QIREVASGAA RIRGETLGII
GLGRVGQAVA LRAKAFGFNV LFYDPYLSDG VERALGLQRV STLQDLLFHS DCVTLHCGLN
EHNHHLINDF TVKQMRQGAF LVNTARGGLV DEKALAQALK EGRIRGAALD VHESEPFSFS
QGPLKDAPNL ICTPHAAWYS EQASIEMREE AAREIRRAIT GRIPDSLKNC VNKDHLTAAT
HWASMDPAVV HPELNGAAYR YPPGVVGVAP TGIPAAVEGI VPSAMSLSHG LPPVAHPPHA
PSPGQTVKPE ADRDHASDQL
//
ID CTNA1_HUMAN Reviewed; 906 AA.
AC P35221; Q12795; Q8N1C0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 11-NOV-2015, entry version 166.
DE RecName: Full=Catenin alpha-1;
DE AltName: Full=Alpha E-catenin;
DE AltName: Full=Cadherin-associated protein;
DE AltName: Full=Renal carcinoma antigen NY-REN-13;
GN Name=CTNNA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8404069;
RA Furukawa Y., Nakatsuru S., Nagafuchi A., Tsukita S., Muto T.,
RA Nakamura Y., Horii A.;
RT "Structure, expression and chromosome assignment of the human catenin
RT (cadherin-associated protein) alpha 1 gene (CTNNA1).";
RL Cytogenet. Cell Genet. 65:74-78(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Colon, and Lung;
RX PubMed=8323564; DOI=10.1006/bbrc.1993.1710;
RA Oda T., Kanai Y., Shimoyama Y., Nagafuchi A., Tsukita S.,
RA Hirohashi S.;
RT "Cloning of the human alpha-catenin cDNA and its aberrant mRNA in a
RT human cancer cell line.";
RL Biochem. Biophys. Res. Commun. 193:897-904(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon;
RX PubMed=7945318; DOI=10.1006/bbrc.1994.2381;
RA Rimm D.L., Kebriaei P., Morrow J.S.;
RT "Molecular cloning reveals alternative splice forms of human alpha(E)-
RT catenin.";
RL Biochem. Biophys. Res. Commun. 203:1691-1699(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING, AND
RP SUBCELLULAR LOCATION (ISOFORM 3).
RC TISSUE=Hippocampus;
RX PubMed=21708131; DOI=10.1016/j.bbrc.2011.06.085;
RA Kask M., Pruunsild P., Timmusk T.;
RT "Bidirectional transcription from human LRRTM2/CTNNA1 and
RT LRRTM1/CTNNA2 gene loci leads to expression of N-terminally truncated
RT CTNNA1 and CTNNA2 isoforms.";
RL Biochem. Biophys. Res. Commun. 411:56-61(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Nollet F.H., Vanpoucke G.G., van Roy F.M.;
RT "Genomic organization of the human alphaE-catenin gene (CTNNA1).";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-179 AND SER-219.
RG NIEHS SNPs program;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-12; 166-178 AND 617-623, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT THR-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Zebisch A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 159-250.
RC TISSUE=Prostate;
RX PubMed=8188230; DOI=10.1006/geno.1994.1042;
RA McPherson J.D., Morton R.A., Ewing C.M., Wasmuth J.J., Overhauser J.,
RA Nagafuchi A., Tsukita S., Isaacs W.B.;
RT "Assignment of the human alpha-catenin gene (CTNNA1) to chromosome
RT 5q21-q22.";
RL Genomics 19:188-190(1994).
RN [12]
RP IDENTIFICATION IN AN E-CADHERIN/CATENIN ADHESION COMPLEX.
RX PubMed=7982500; DOI=10.1016/0014-5793(94)01205-9;
RA Butz S., Kemler R.;
RT "Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell
RT adhesion.";
RL FEBS Lett. 355:195-200(1994).
RN [13]
RP SUBUNIT, AND INTERACTION WITH CTNNB1.
RX PubMed=9341178; DOI=10.1074/jbc.272.43.27301;
RA Koslov E.R., Maupin P., Pradhan D., Morrow J.S., Rimm D.L.;
RT "Alpha-catenin can form asymmetric homodimeric complexes and/or
RT heterodimeric complexes with beta-catenin.";
RL J. Biol. Chem. 272:27301-27306(1997).
RN [14]
RP INTERACTION WITH JUP; CTNNB1 AND ALPHA-ACTININ.
RX PubMed=9152027;
RA Nieset J.E., Redfield A.R., Jin F., Knudsen K.A., Johnson K.R.,
RA Wheelock M.J.;
RT "Characterization of the interactions of alpha-catenin with alpha-
RT actinin and beta-catenin/plakoglobin.";
RL J. Cell Sci. 110:1013-1022(1997).
RN [15]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [16]
RP INTERACTION WITH AJUBA.
RX PubMed=12417594; DOI=10.1074/jbc.M205391200;
RA Marie H., Pratt S.J., Betson M., Epple H., Kittler J.T., Meek L.,
RA Moss S.J., Troyanovsky S., Attwell D., Longmore G.D., Braga V.M.;
RT "The LIM protein Ajuba is recruited to cadherin-dependent cell
RT junctions through an association with alpha-catenin.";
RL J. Biol. Chem. 278:1220-1228(2003).
RN [17]
RP SUMOYLATION.
RX PubMed=15561718; DOI=10.1074/jbc.M411718200;
RA Gocke C.B., Yu H., Kang J.;
RT "Systematic identification and analysis of mammalian small ubiquitin-
RT like modifier substrates.";
RL J. Biol. Chem. 280:5004-5012(2005).
RN [18]
RP INTERACTION WITH ARHGAP21.
RX PubMed=16184169; DOI=10.1038/ncb1308;
RA Sousa S., Cabanes D., Archambaud C., Colland F., Lemichez E.,
RA Popoff M., Boisson-Dupuis S., Gouin E., Lecuit M., Legrain P.,
RA Cossart P.;
RT "ARHGAP10 is necessary for alpha-catenin recruitment at adherens
RT junctions and for Listeria invasion.";
RL Nat. Cell Biol. 7:954-960(2005).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pituitary;
RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x;
RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.;
RT "Phosphoproteomic analysis of the human pituitary.";
RL Pituitary 9:109-120(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate
RT cancer cells: identification of phosphoproteins in the LNCaP cell
RT line.";
RL Electrophoresis 28:2027-2034(2007).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641 AND SER-652, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP INTERACTION WITH LIMA1.
RX PubMed=18093941; DOI=10.1073/pnas.0710504105;
RA Abe K., Takeichi M.;
RT "EPLIN mediates linkage of the cadherin catenin complex to F-actin and
RT stabilizes the circumferential actin belt.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:13-19(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641 AND THR-645, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-634; SER-641 AND
RP SER-652, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264; SER-268; SER-295;
RP SER-297; THR-634; SER-641 AND SER-851, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 377-632, PARTIAL PROTEIN
RP SEQUENCE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11447106; DOI=10.1093/emboj/20.14.3645;
RA Yang J., Dokurno P., Tonks N.K., Barford D.;
RT "Crystal structure of the M-fragment of alpha-catenin: implications
RT for modulation of cell adhesion.";
RL EMBO J. 20:3645-3656(2001).
RN [35]
RP POSSIBLE INVOLVEMENT IN HDGC.
RX PubMed=23208944; DOI=10.1002/path.4152;
RA Majewski I.J., Kluijt I., Cats A., Scerri T.S., de Jong D.,
RA Kluin R.J., Hansford S., Hogervorst F.B., Bosma A.J., Hofland I.,
RA Winter M., Huntsman D., Jonkers J., Bahlo M., Bernards R.;
RT "An alpha-E-catenin (CTNNA1) mutation in hereditary diffuse gastric
RT cancer.";
RL J. Pathol. 229:621-629(2013).
CC -!- FUNCTION: Associates with the cytoplasmic domain of a variety of
CC cadherins. The association of catenins to cadherins produces a
CC complex which is linked to the actin filament network, and which
CC seems to be of primary importance for cadherins cell-adhesion
CC properties. Can associate with both E- and N-cadherins. Originally
CC believed to be a stable component of E-cadherin/catenin adhesion
CC complexes and to mediate the linkage of cadherins to the actin
CC cytoskeleton at adherens junctions. In contrast, cortical actin
CC was found to be much more dynamic than E-cadherin/catenin
CC complexes and CTNNA1 was shown not to bind to F-actin when
CC assembled in the complex suggesting a different linkage between
CC actin and adherens junctions components. The homodimeric form may
CC regulate actin filament assembly and inhibit actin branching by
CC competing with the Arp2/3 complex for binding to actin filaments.
CC May play a crucial role in cell differentiation.
CC -!- SUBUNIT: Monomer and homodimer; the monomer preferentially binds
CC to CTNNB1 and the homodimer to actin. Binds MLLT4 and F-actin.
CC Possible component of an E-cadherin/ catenin adhesion complex
CC together with E-cadherin/CDH1 and beta-catenin/CTNNB1 or gamma-
CC catenin/JUP; the complex is located to adherens junctions. The
CC stable association of CTNNA1 is controversial as CTNNA1 was shown
CC not to bind to F-actin when assembled in the complex.
CC Alternatively, the CTNNA1-containing complex may be linked to F-
CC actin by other proteins such as LIMA1. Interacts with ARHGAP21 and
CC with AJUBA. Interacts with LIMA1 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P25054:APC; NbExp=2; IntAct=EBI-701918, EBI-727707;
CC P32121:ARRB2; NbExp=3; IntAct=EBI-701918, EBI-714559;
CC P00533:EGFR; NbExp=4; IntAct=EBI-701918, EBI-297353;
CC P14923:JUP; NbExp=2; IntAct=EBI-701918, EBI-702484;
CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm, cytoskeleton. Cell
CC junction, adherens junction. Cell membrane; Peripheral membrane
CC protein; Cytoplasmic side. Cell junction. Note=Found at cell-cell
CC boundaries and probably at cell-matrix boundaries.
CC -!- SUBCELLULAR LOCATION: Isoform 3: Cell membrane
CC {ECO:0000269|PubMed:21708131}; Peripheral membrane protein
CC {ECO:0000269|PubMed:21708131}; Cytoplasmic side
CC {ECO:0000269|PubMed:21708131}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=CTNNA1a;
CC IsoId=P35221-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35221-2; Sequence=VSP_017494;
CC Name=3; Synonyms=CTNNA1b;
CC IsoId=P35221-3; Sequence=VSP_047810;
CC Note=Expressed at high levels in the nervous system. Lacks the
CC beta-catenin interaction domain.;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously in normal tissues.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:15561718}.
CC -!- DISEASE: Hereditary diffuse gastric cancer (HDGC) [MIM:137215]: A
CC cancer predisposition syndrome with increased susceptibility to
CC diffuse gastric cancer. Diffuse gastric cancer is a malignant
CC disease characterized by poorly differentiated infiltrating
CC lesions resulting in thickening of the stomach. Malignant tumors
CC start in the stomach, can spread to the esophagus or the small
CC intestine, and can extend through the stomach wall to nearby lymph
CC nodes and organs. It also can metastasize to other parts of the
CC body. {ECO:0000269|PubMed:23208944}. Note=The gene represented in
CC this entry may be involved in disease pathogenesis.
CC -!- SIMILARITY: Belongs to the vinculin/alpha-catenin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ctnna1/";
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DR EMBL; D14705; BAA03530.1; -; mRNA.
DR EMBL; D13866; BAA02979.1; -; mRNA.
DR EMBL; L23805; AAA86430.1; -; mRNA.
DR EMBL; U03100; AAA18949.1; -; mRNA.
DR EMBL; HQ589335; AEF32483.1; -; mRNA.
DR EMBL; AF102803; AAC99459.1; -; Genomic_DNA.
DR EMBL; AF102787; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102788; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102789; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102790; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102791; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102792; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102793; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102794; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102795; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102796; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102797; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102798; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102799; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102800; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102801; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AF102802; AAC99459.1; JOINED; Genomic_DNA.
DR EMBL; AY884207; AAW56940.1; -; Genomic_DNA.
DR EMBL; AC010453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011405; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034243; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC113340; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62124.1; -; Genomic_DNA.
DR EMBL; BC000385; AAH00385.1; -; mRNA.
DR EMBL; BC031262; AAH31262.1; -; mRNA.
DR EMBL; L22080; AAA35502.1; -; mRNA.
DR CCDS; CCDS34243.1; -. [P35221-1]
DR CCDS; CCDS75315.1; -. [P35221-3]
DR PIR; JC2542; JC2542.
DR PIR; JN0607; JN0607.
DR RefSeq; NP_001277236.1; NM_001290307.1.
DR RefSeq; NP_001277238.1; NM_001290309.1.
DR RefSeq; NP_001277239.1; NM_001290310.1.
DR RefSeq; NP_001277241.1; NM_001290312.1. [P35221-3]
DR RefSeq; NP_001894.2; NM_001903.3. [P35221-1]
DR RefSeq; XP_005271956.1; XM_005271899.2. [P35221-3]
DR RefSeq; XP_006714599.1; XM_006714536.2. [P35221-1]
DR RefSeq; XP_011541474.1; XM_011543172.1. [P35221-1]
DR UniGene; Hs.445981; -.
DR PDB; 1H6G; X-ray; 2.20 A; A/B=377-632.
DR PDB; 4EHP; X-ray; 2.66 A; B=277-382.
DR PDB; 4IGG; X-ray; 3.66 A; A/B=82-906.
DR PDBsum; 1H6G; -.
DR PDBsum; 4EHP; -.
DR PDBsum; 4IGG; -.
DR ProteinModelPortal; P35221; -.
DR SMR; P35221; 19-878.
DR BioGrid; 107876; 57.
DR DIP; DIP-515N; -.
DR IntAct; P35221; 40.
DR MINT; MINT-4998962; -.
DR STRING; 9606.ENSP00000304669; -.
DR PhosphoSite; P35221; -.
DR BioMuta; CTNNA1; -.
DR DMDM; 461853; -.
DR MaxQB; P35221; -.
DR PaxDb; P35221; -.
DR PeptideAtlas; P35221; -.
DR PRIDE; P35221; -.
DR DNASU; 1495; -.
DR Ensembl; ENST00000302763; ENSP00000304669; ENSG00000044115. [P35221-1]
DR Ensembl; ENST00000540387; ENSP00000438476; ENSG00000044115. [P35221-3]
DR GeneID; 1495; -.
DR KEGG; hsa:1495; -.
DR UCSC; uc003ldh.3; human. [P35221-1]
DR CTD; 1495; -.
DR GeneCards; CTNNA1; -.
DR HGNC; HGNC:2509; CTNNA1.
DR HPA; CAB021089; -.
DR HPA; HPA046119; -.
DR MIM; 116805; gene.
DR MIM; 137215; phenotype.
DR neXtProt; NX_P35221; -.
DR PharmGKB; PA27008; -.
DR eggNOG; KOG3681; Eukaryota.
DR eggNOG; ENOG410XSRU; LUCA.
DR GeneTree; ENSGT00550000074411; -.
DR HOGENOM; HOG000280724; -.
DR HOVERGEN; HBG000069; -.
DR InParanoid; P35221; -.
DR KO; K05691; -.
DR OMA; WERQVRV; -.
DR OrthoDB; EOG7HQN7B; -.
DR PhylomeDB; P35221; -.
DR TreeFam; TF313686; -.
DR Reactome; R-HSA-375170; CDO in myogenesis.
DR Reactome; R-HSA-418990; Adherens junctions interactions.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-5626467; RHO GTPases activate IQGAPs.
DR ChiTaRS; CTNNA1; human.
DR EvolutionaryTrace; P35221; -.
DR GeneWiki; Catenin_(cadherin-associated_protein),_alpha_1; -.
DR GenomeRNAi; 1495; -.
DR NextBio; 6145; -.
DR PRO; PR:P35221; -.
DR Proteomes; UP000005640; Chromosome 5.
DR Bgee; P35221; -.
DR CleanEx; HS_CTNNA1; -.
DR ExpressionAtlas; P35221; baseline and differential.
DR Genevisible; P35221; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:InterPro.
DR GO; GO:0016342; C:catenin complex; IDA:BHF-UCL.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016600; C:flotillin complex; IEA:Ensembl.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005915; C:zonula adherens; IEA:Ensembl.
DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; IPI:UniProtKB.
DR GO; GO:0045295; F:gamma-catenin binding; IPI:BHF-UCL.
DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0017166; F:vinculin binding; IPI:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IEA:InterPro.
DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0043297; P:apical junction assembly; NAS:UniProtKB.
DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl.
DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0045216; P:cell-cell junction organization; TAS:Reactome.
DR GO; GO:0034613; P:cellular protein localization; IEA:Ensembl.
DR GO; GO:0071681; P:cellular response to indole-3-methanol; IDA:UniProtKB.
DR GO; GO:0090136; P:epithelial cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IEA:Ensembl.
DR GO; GO:0016264; P:gap junction assembly; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0042692; P:muscle cell differentiation; TAS:Reactome.
DR GO; GO:2000146; P:negative regulation of cell motility; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:2001045; P:negative regulation of integrin-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome.
DR InterPro; IPR001033; Alpha_catenin.
DR InterPro; IPR030047; CTNNA1.
DR InterPro; IPR006077; Vinculin/catenin.
DR InterPro; IPR000633; Vinculin_CS.
DR PANTHER; PTHR18914; PTHR18914; 1.
DR PANTHER; PTHR18914:SF24; PTHR18914:SF24; 1.
DR Pfam; PF01044; Vinculin; 2.
DR PRINTS; PR00805; ALPHACATENIN.
DR SUPFAM; SSF47220; SSF47220; 4.
DR PROSITE; PS00663; VINCULIN_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell adhesion;
KW Cell junction; Cell membrane; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Membrane; Phosphoprotein;
KW Polymorphism; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed. {ECO:0000269|Ref.10}.
FT CHAIN 2 906 Catenin alpha-1.
FT /FTId=PRO_0000064261.
FT REGION 2 228 Involved in homodimerization.
FT REGION 97 148 Interaction with JUP and CTNNB1.
FT REGION 325 394 Interaction with alpha-actinin.
FT MOD_RES 2 2 N-acetylthreonine. {ECO:0000269|Ref.10}.
FT MOD_RES 264 264 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 268 268 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 295 295 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 297 297 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 634 634 Phosphothreonine.
FT {ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:24275569}.
FT MOD_RES 641 641 Phosphoserine.
FT {ECO:0000244|PubMed:16807684,
FT ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:18220336,
FT ECO:0000244|PubMed:18318008,
FT ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:19369195,
FT ECO:0000244|PubMed:19690332,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:24275569}.
FT MOD_RES 645 645 Phosphothreonine.
FT {ECO:0000244|PubMed:18318008}.
FT MOD_RES 652 652 Phosphoserine.
FT {ECO:0000244|PubMed:17487921,
FT ECO:0000244|PubMed:18669648,
FT ECO:0000244|PubMed:21406692}.
FT MOD_RES 655 655 Phosphoserine.
FT {ECO:0000250|UniProtKB:P26231}.
FT MOD_RES 658 658 Phosphothreonine.
FT {ECO:0000250|UniProtKB:P26231}.
FT MOD_RES 851 851 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT VAR_SEQ 1 370 Missing (in isoform 3).
FT {ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:21708131}.
FT /FTId=VSP_047810.
FT VAR_SEQ 811 811 G -> GNCDTCGALQGLKGWPPPLCLATHW (in
FT isoform 2). {ECO:0000303|PubMed:7945318}.
FT /FTId=VSP_017494.
FT VARIANT 179 179 A -> V (in dbSNP:rs28363394).
FT {ECO:0000269|Ref.6}.
FT /FTId=VAR_022303.
FT VARIANT 219 219 P -> S (in dbSNP:rs28363406).
FT {ECO:0000269|Ref.6}.
FT /FTId=VAR_022304.
FT CONFLICT 92 92 A -> V (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 129 129 R -> P (in Ref. 3; AAA18949).
FT {ECO:0000305}.
FT CONFLICT 175 175 I -> N (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 216 216 K -> S (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 342 342 Q -> K (in Ref. 1; BAA03530).
FT {ECO:0000305}.
FT CONFLICT 344 348 LQDLL -> CRTCV (in Ref. 3; AAA86430).
FT {ECO:0000305}.
FT CONFLICT 460 460 L -> G (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 469 469 L -> TW (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 473 473 A -> P (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 653 653 R -> E (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 685 685 A -> R (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 764 764 A -> R (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT CONFLICT 789 789 Q -> H (in Ref. 1; BAA03530).
FT {ECO:0000305}.
FT CONFLICT 859 859 W -> M (in Ref. 3; AAA86430/AAA18949).
FT {ECO:0000305}.
FT HELIX 293 299 {ECO:0000244|PDB:4EHP}.
FT STRAND 300 302 {ECO:0000244|PDB:4EHP}.
FT HELIX 305 316 {ECO:0000244|PDB:4EHP}.
FT HELIX 325 327 {ECO:0000244|PDB:4EHP}.
FT HELIX 328 352 {ECO:0000244|PDB:4EHP}.
FT HELIX 353 355 {ECO:0000244|PDB:4EHP}.
FT HELIX 378 386 {ECO:0000244|PDB:1H6G}.
FT HELIX 387 389 {ECO:0000244|PDB:1H6G}.
FT TURN 393 395 {ECO:0000244|PDB:1H6G}.
FT HELIX 398 409 {ECO:0000244|PDB:1H6G}.
FT HELIX 413 438 {ECO:0000244|PDB:1H6G}.
FT HELIX 444 473 {ECO:0000244|PDB:1H6G}.
FT HELIX 478 506 {ECO:0000244|PDB:1H6G}.
FT HELIX 509 531 {ECO:0000244|PDB:1H6G}.
FT HELIX 535 559 {ECO:0000244|PDB:1H6G}.
FT TURN 560 562 {ECO:0000244|PDB:1H6G}.
FT HELIX 567 581 {ECO:0000244|PDB:1H6G}.
FT HELIX 583 598 {ECO:0000244|PDB:1H6G}.
FT STRAND 600 602 {ECO:0000244|PDB:1H6G}.
FT HELIX 608 630 {ECO:0000244|PDB:1H6G}.
SQ SEQUENCE 906 AA; 100071 MW; 7AAE6F5DDBAF5099 CRC64;
MTAVHAGNIN FKWDPKSLEI RTLAVERLLE PLVTQVTTLV NTNSKGPSNK KRGRSKKAHV
LAASVEQATE NFLEKGDKIA KESQFLKEEL VAAVEDVRKQ GDLMKAAAGE FADDPCSSVK
RGNMVRAARA LLSAVTRLLI LADMADVYKL LVQLKVVEDG ILKLRNAGNE QDLGIQYKAL
KPEVDKLNIM AAKRQQELKD VGHRDQMAAA RGILQKNVPI LYTASQACLQ HPDVAAYKAN
RDLIYKQLQQ AVTGISNAAQ ATASDDASQH QGGGGGELAY ALNNFDKQII VDPLSFSEER
FRPSLEERLE SIISGAALMA DSSCTRDDRR ERIVAECNAV RQALQDLLSE YMGNAGRKER
SDALNSAIDK MTKKTRDLRR QLRKAVMDHV SDSFLETNVP LLVLIEAAKN GNEKEVKEYA
QVFREHANKL IEVANLACSI SNNEEGVKLV RMSASQLEAL CPQVINAALA LAAKPQSKLA
QENMDLFKEQ WEKQVRVLTD AVDDITSIDD FLAVSENHIL EDVNKCVIAL QEKDVDGLDR
TAGAIRGRAA RVIHVVTSEM DNYEPGVYTE KVLEATKLLS NTVMPRFTEQ VEAAVEALSS
DPAQPMDENE FIDASRLVYD GIRDIRKAVL MIRTPEELDD SDFETEDFDV RSRTSVQTED
DQLIAGQSAR AIMAQLPQEQ KAKIAEQVAS FQEEKSKLDA EVSKWDDSGN DIIVLAKQMC
MIMMEMTDFT RGKGPLKNTS DVISAAKKIA EAGSRMDKLG RTIADHCPDS ACKQDLLAYL
QRIALYCHQL NICSKVKAEV QNLGGELVVS GVDSAMSLIQ AAKNLMNAVV QTVKASYVAS
TKYQKSQGMA SLNLPAVSWK MKAPEKKPLV KREKQDETQT KIKRASQKKH VNPVQALSEF
KAMDSI
//
ID HDAC2_HUMAN Reviewed; 488 AA.
AC Q92769; B3KRS5; B4DL58; E1P561; Q5SRI8; Q5SZ86; Q8NEH4;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 11-NOV-2015, entry version 177.
DE RecName: Full=Histone deacetylase 2;
DE Short=HD2;
DE EC=3.5.1.98;
GN Name=HDAC2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT CYS-230.
RC TISSUE=Mammary gland;
RX PubMed=8917507; DOI=10.1073/pnas.93.23.12845;
RA Yang W.-M., Inouye C.J., Zeng Y., Bearss D., Seto E.;
RT "Transcriptional repression by YY1 is mediated by interaction with a
RT mammalian homolog of the yeast global regulator RPD3.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12845-12850(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP HIS-315.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH ATR, AND IDENTIFICATION IN A COMPLEX CONTAINING ATR
RP AND CHD4.
RX PubMed=10545197; DOI=10.1021/bi991614n;
RA Schmidt D.R., Schreiber S.L.;
RT "Molecular association between ATR and two components of the
RT nucleosome remodeling and deacetylating complex, HDAC2 and CHD4.";
RL Biochemistry 38:14711-14717(1999).
RN [7]
RP INTERACTION WITH SNW1.
RX PubMed=10644367; DOI=10.1128/JVI.74.4.1939-1947.2000;
RA Zhou S., Fujimuro M., Hsieh J.J., Chen L., Hayward S.D.;
RT "A role for SKIP in EBNA2 activation of CBF1-repressed promoters.";
RL J. Virol. 74:1939-1947(2000).
RN [8]
RP INTERACTION WITH DNMT1 AND DMAP1.
RX PubMed=10888872; DOI=10.1038/77023;
RA Rountree M.R., Bachman K.E., Baylin S.B.;
RT "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at
RT replication foci.";
RL Nat. Genet. 25:269-277(2000).
RN [9]
RP REVIEW ON DEACETYLASE COMPLEXES.
RX PubMed=10904264; DOI=10.1016/S0168-9525(00)02066-7;
RA Ahringer J.;
RT "NuRD and SIN3 histone deacetylase complexes in development.";
RL Trends Genet. 16:351-356(2000).
RN [10]
RP INTERACTION WITH MINT.
RX PubMed=11331609; DOI=10.1101/gad.871201;
RA Shi Y., Downes M., Xie W., Kao H.-Y., Ordentlich P., Tsai C.-C.,
RA Hon M., Evans R.M.;
RT "Sharp, an inducible cofactor that integrates nuclear receptor
RT repression and activation.";
RL Genes Dev. 15:1140-1151(2001).
RN [11]
RP INTERACTION WITH CBFA2T3.
RX PubMed=11533236; DOI=10.1128/MCB.21.19.6470-6483.2001;
RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N.,
RA Downing J.R., Meyers S., Hiebert S.W.;
RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts
RT with multiple histone deacetylases and binds mSin3A through its
RT oligomerization domain.";
RL Mol. Cell. Biol. 21:6470-6483(2001).
RN [12]
RP INTERACTION WITH HDAC10.
RX PubMed=11739383; DOI=10.1074/jbc.M108055200;
RA Fischer D.D., Cai R., Bhatia U., Asselbergs F.A.M., Song C., Terry R.,
RA Trogani N., Widmer R., Atadja P., Cohen D.;
RT "Isolation and characterization of a novel class II histone
RT deacetylase, HDAC10.";
RL J. Biol. Chem. 277:6656-6666(2002).
RN [13]
RP INTERACTION WITH SP3.
RX PubMed=12176973; DOI=10.1074/jbc.C200378200;
RA Sun J.M., Chen H.Y., Moniwa M., Litchfield D.W., Seto E., Davie J.R.;
RT "The transcriptional repressor Sp3 is associated with CK2-
RT phosphorylated histone deacetylase 2.";
RL J. Biol. Chem. 277:35783-35786(2002).
RN [14]
RP INTERACTION WITH DAXX AND DEK.
RX PubMed=12140263;
RA Hollenbach A.D., McPherson C.J., Mientjes E.J., Iyengar R.,
RA Grosveld G.;
RT "Daxx and histone deacetylase II associate with chromatin through an
RT interaction with core histones and the chromatin-associated protein
RT Dek.";
RL J. Cell Sci. 115:3319-3330(2002).
RN [15]
RP INTERACTION WITH BCL6.
RX PubMed=12402037; DOI=10.1038/ng1018;
RA Bereshchenko O.R., Gu W., Dalla-Favera R.;
RT "Acetylation inactivates the transcriptional repressor BCL6.";
RL Nat. Genet. 32:606-613(2002).
RN [16]
RP INTERACTION WITH APEX1.
RX PubMed=14633989; DOI=10.1093/emboj/cdg595;
RA Bhakat K.K., Izumi T., Yang S.H., Hazra T.K., Mitra S.;
RT "Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation
RT of the parathyroid hormone gene.";
RL EMBO J. 22:6299-6309(2003).
RN [17]
RP INTERACTION WITH HCFC1.
RX PubMed=12670868; DOI=10.1101/gad.252103;
RA Wysocka J., Myers M.P., Laherty C.D., Eisenman R.N., Herr W.;
RT "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4
RT methyltransferase are tethered together selectively by the cell-
RT proliferation factor HCF-1.";
RL Genes Dev. 17:896-911(2003).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE BHC
RP COMPLEX WITH PHF21A; HDAC1; HMG20B; KDM1A; RCOR1; ZMYM2; ZNF217;
RP ZMYM3; KIAA0182 AND GTF2I.
RX PubMed=12493763; DOI=10.1074/jbc.M208992200;
RA Hakimi M.-A., Dong Y., Lane W.S., Speicher D.W., Shiekhattar R.;
RT "A candidate X-linked mental retardation gene is a component of a new
RT family of histone deacetylase-containing complexes.";
RL J. Biol. Chem. 278:7234-7239(2003).
RN [19]
RP IDENTIFICATION IN A MSIN3A COREPRESSOR COMPLEX WITH SIN3A; SAP130;
RP SUDS3; ARID4B; HDAC1 AND HDAC2.
RX PubMed=12724404; DOI=10.1128/MCB.23.10.3456-3467.2003;
RA Fleischer T.C., Yun U.J., Ayer D.E.;
RT "Identification and characterization of three new components of the
RT mSin3A corepressor complex.";
RL Mol. Cell. Biol. 23:3456-3467(2003).
RN [20]
RP INTERACTION WITH PELP1.
RX PubMed=15456770; DOI=10.1074/jbc.M406831200;
RA Choi Y.B., Ko J.K., Shin J.;
RT "The transcriptional corepressor, PELP1, recruits HDAC2 and masks
RT histones using two separate domains.";
RL J. Biol. Chem. 279:50930-50941(2004).
RN [21]
RP INTERACTION WITH NRIP1.
RX PubMed=15060175; DOI=10.1093/nar/gkh524;
RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P.,
RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.;
RT "Multiple domains of the receptor-interacting protein 140 contribute
RT to transcription inhibition.";
RL Nucleic Acids Res. 32:1957-1966(2004).
RN [22]
RP INTERACTION WITH JMJD2A.
RX PubMed=15927959; DOI=10.1074/jbc.M413687200;
RA Gray S.G., Iglesias A.H., Lizcano F., Villanueva R., Camelo S.,
RA Jingu H., Teh B.T., Koibuchi N., Chin W.W., Kokkotou E., Dangond F.;
RT "Functional characterization of JMJD2A, a histone deacetylase- and
RT retinoblastoma-binding protein.";
RL J. Biol. Chem. 280:28507-28518(2005).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND
RP SER-424, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [24]
RP INTERACTION WITH SAP30L.
RX PubMed=16820529; DOI=10.1093/nar/gkl401;
RA Viiri K.M., Korkeamaeki H., Kukkonen M.K., Nieminen L.K., Lindfors K.,
RA Peterson P., Maeki M., Kainulainen H., Lohi O.;
RT "SAP30L interacts with members of the Sin3A corepressor complex and
RT targets Sin3A to the nucleolus.";
RL Nucleic Acids Res. 34:3288-3298(2006).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [26]
RP IDENTIFICATION IN A COMPLEX WITH CDYL; MIER1; MIER2 AND HDAC1.
RX PubMed=19061646; DOI=10.1016/j.molcel.2008.10.025;
RA Mulligan P., Westbrook T.F., Ottinger M., Pavlova N., Chang B.,
RA Macia E., Shi Y.J., Barretina J., Liu J., Howley P.M., Elledge S.J.,
RA Shi Y.;
RT "CDYL bridges REST and histone methyltransferases for gene repression
RT and suppression of cellular transformation.";
RL Mol. Cell 32:718-726(2008).
RN [27]
RP INTERACTION WITH BCL6.
RX PubMed=18212045; DOI=10.1128/MCB.01400-07;
RA Mendez L.M., Polo J.M., Yu J.J., Krupski M., Ding B.B., Melnick A.,
RA Ye B.H.;
RT "CtBP is an essential corepressor for BCL6 autoregulation.";
RL Mol. Cell. Biol. 28:2175-2186(2008).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [29]
RP INTERACTION WITH FAM64A.
RX PubMed=18757745; DOI=10.1073/pnas.0709227105;
RA Zhao W.M., Coppinger J.A., Seki A., Cheng X.L., Yates J.R. III,
RA Fang G.;
RT "RCS1, a substrate of APC/C, controls the metaphase to anaphase
RT transition.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:13415-13420(2008).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [31]
RP FUNCTION, AND INTERACTION WITH TSHZ3.
RX PubMed=19343227; DOI=10.1371/journal.pone.0005071;
RA Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J.,
RA Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D.;
RT "FE65 binds Teashirt, inhibiting expression of the primate-specific
RT caspase-4.";
RL PLoS ONE 4:E5071-E5071(2009).
RN [32]
RP INTERACTION WITH CHFR.
RX PubMed=19182791; DOI=10.1038/ncb1837;
RA Oh Y.M., Kwon Y.E., Kim J.M., Bae S.J., Lee B.K., Yoo S.J.,
RA Chung C.H., Deshaies R.J., Seol J.H.;
RT "Chfr is linked to tumour metastasis through the downregulation of
RT HDAC1.";
RL Nat. Cell Biol. 11:295-302(2009).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394 AND SER-422, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND
RP SER-424, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [35]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [36]
RP FUNCTION, AND INTERACTION WITH MTA1.
RX PubMed=21965678; DOI=10.1074/jbc.M111.267237;
RA Cong L., Pakala S.B., Ohshiro K., Li D.Q., Kumar R.;
RT "SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor
RT antigen 1 (MTA1) synergistically regulate its transcriptional
RT repressor function.";
RL J. Biol. Chem. 286:43793-43808(2011).
RN [37]
RP INTERACTION WITH BEND3.
RX PubMed=21914818; DOI=10.1242/jcs.086603;
RA Sathyan K.M., Shen Z., Tripathi V., Prasanth K.V., Prasanth S.G.;
RT "A BEN-domain-containing protein associates with heterochromatin and
RT represses transcription.";
RL J. Cell Sci. 124:3149-3163(2011).
RN [38]
RP INTERACTION WITH SMARCAD1.
RX PubMed=21549307; DOI=10.1016/j.molcel.2011.02.036;
RA Rowbotham S.P., Barki L., Neves-Costa A., Santos F., Dean W.,
RA Hawkes N., Choudhary P., Will W.R., Webster J., Oxley D., Green C.M.,
RA Varga-Weisz P., Mermoud J.E.;
RT "Maintenance of silent chromatin through replication requires SWI/SNF-
RT like chromatin remodeler SMARCAD1.";
RL Mol. Cell 42:285-296(2011).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND
RP SER-424, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [40]
RP INTERACTION WITH NACC2.
RX PubMed=22926524; DOI=10.1038/onc.2012.386;
RA Xuan C., Wang Q., Han X., Duan Y., Li L., Shi L., Wang Y., Shan L.,
RA Yao Z., Shang Y.;
RT "RBB, a novel transcription repressor, represses the transcription of
RT HDM2 oncogene.";
RL Oncogene 32:3711-3721(2013).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND
RP SER-424, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [42]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-462, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [43]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MTA1.
RX PubMed=24970816;
RA Liu J., Xu D., Wang H., Zhang Y., Chang Y., Zhang J., Wang J., Li C.,
RA Liu H., Zhao M., Lin C., Zhan Q., Huang C., Qian H.;
RT "The subcellular distribution and function of MTA1 in cancer
RT differentiation.";
RL Oncotarget 5:5153-5164(2014).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 9-374 IN COMPLEX WITH
RP SUBSTITUTED N-(2-AMINOPHENYL)BENZAMIDE INHIBITORS.
RX PubMed=20392638; DOI=10.1016/j.bmcl.2010.03.091;
RA Bressi J.C., Jennings A.J., Skene R., Wu Y., Melkus R., De Jong R.,
RA O'Connell S., Grimshaw C.E., Navre M., Gangloff A.R.;
RT "Exploration of the HDAC2 foot pocket: Synthesis and SAR of
RT substituted N-(2-aminophenyl)benzamides.";
RL Bioorg. Med. Chem. Lett. 20:3142-3145(2010).
CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on
CC the N-terminal part of the core histones (H2A, H2B, H3 and H4).
CC Histone deacetylation gives a tag for epigenetic repression and
CC plays an important role in transcriptional regulation, cell cycle
CC progression and developmental events. Histone deacetylases act via
CC the formation of large multiprotein complexes. Forms
CC transcriptional repressor complexes by associating with MAD, SIN3,
CC YY1 and N-COR. Interacts in the late S-phase of DNA-replication
CC with DNMT1 in the other transcriptional repressor complex composed
CC of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its
CC transcriptional repressor activity. Component of a
CC RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone
CC deacetylase (HDAC) recruitment, a number of genes implicated in
CC multilineage blood cell development. May be involved in the
CC transcriptional repression of circadian target genes, such as
CC PER1, mediated by CRY1 through histone deacetylation. Involved in
CC MTA1-mediated transcriptional corepression of TFF1 and CDKN1A.
CC {ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:21965678}.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of
CC a histone to yield a deacetylated histone.
CC -!- SUBUNIT: Part of the core histone deacetylase (HDAC) complex
CC composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core complex
CC associates with MTA2, MBD3, MTA1L1, CHD3 and CHD4 to form the
CC nucleosome remodeling and histone deacetylation (NuRD) complex, or
CC with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex.
CC Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly
CC with GFI1 and GFI1B. Interacts with SNW1, HDAC7, PRDM6, SAP30,
CC SETDB1 and SUV39H1. Interacts with the H2AFY (via the non-histone
CC region). Component of a BHC histone deacetylase complex that
CC contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC
CC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I.
CC Part of a complex containing the core histones H2A, H2B, H3 and
CC H4, DEK and unphosphorylated DAXX. Part of a complex containing
CC ATR and CHD4. Forms a heterologous complex at least with YY1.
CC Interacts with ATR, CBFA2T3, DNMT1, MINT, HDAC10, HCFC1, NRIP1,
CC KDM4A and PELP1. Component of a mSin3A corepressor complex that
CC contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2. Interacts
CC with CHFR and SAP30L. Interacts (CK2 phosphorylated form) with
CC SP3. Interacts with TSHZ3 (via its N-terminus). Interacts with
CC APEX1; the interaction is not dependent on the acetylated status
CC of APEX1. Part of a complex composed of TRIM28, HDAC1, HDAC2 and
CC EHMT2. Interacts with FAM64A. Interacts with BCL6 (non-acetylated
CC form). Part of a complex containing at least CDYL, MIER1, MIER2,
CC HDAC1 and HDAC2. Interacts with CRY1, INSM1 and ZNF431. Interacts
CC with NACC2. Interacts with MTA1, with a preference for sumoylated
CC MTA1. Interacts with SIX3 (By similarity). Interacts with BEND3.
CC {ECO:0000250|UniProtKB:P70288, ECO:0000269|PubMed:10545197,
CC ECO:0000269|PubMed:10644367, ECO:0000269|PubMed:10888872,
CC ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:11533236,
CC ECO:0000269|PubMed:11739383, ECO:0000269|PubMed:12140263,
CC ECO:0000269|PubMed:12176973, ECO:0000269|PubMed:12402037,
CC ECO:0000269|PubMed:12493763, ECO:0000269|PubMed:12670868,
CC ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:14633989,
CC ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:15456770,
CC ECO:0000269|PubMed:15927959, ECO:0000269|PubMed:16820529,
CC ECO:0000269|PubMed:18212045, ECO:0000269|PubMed:18757745,
CC ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:19182791,
CC ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:20392638,
CC ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:21914818,
CC ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:22926524,
CC ECO:0000269|PubMed:24970816}.
CC -!- INTERACTION:
CC Q9C0K0:BCL11B; NbExp=3; IntAct=EBI-301821, EBI-6597578;
CC Q9HCU9:BRMS1; NbExp=4; IntAct=EBI-301821, EBI-714781;
CC Q9UER7:DAXX; NbExp=2; IntAct=EBI-301821, EBI-77321;
CC P51610:HCFC1; NbExp=2; IntAct=EBI-301821, EBI-396176;
CC Q13547:HDAC1; NbExp=10; IntAct=EBI-301821, EBI-301834;
CC Q2HR82:K8 (xeno); NbExp=7; IntAct=EBI-301821, EBI-9006943;
CC Q9UIS9:MBD1; NbExp=2; IntAct=EBI-301821, EBI-867196;
CC Q13330:MTA1; NbExp=4; IntAct=EBI-301821, EBI-714236;
CC P01106:MYC; NbExp=2; IntAct=EBI-301821, EBI-447544;
CC P06748:NPM1; NbExp=2; IntAct=EBI-301821, EBI-78579;
CC P48382:RFX5; NbExp=4; IntAct=EBI-301821, EBI-923266;
CC Q96ST3:SIN3A; NbExp=5; IntAct=EBI-301821, EBI-347218;
CC O95863:SNAI1; NbExp=2; IntAct=EBI-301821, EBI-1045459;
CC Q9HD15:SRA1; NbExp=2; IntAct=EBI-301821, EBI-727136;
CC O43463:SUV39H1; NbExp=3; IntAct=EBI-301821, EBI-349968;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24970816}.
CC Cytoplasm {ECO:0000269|PubMed:24970816}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92769-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92769-3; Sequence=VSP_056175;
CC Note=No experimental confirmation available.;
CC -!- TISSUE SPECIFICITY: Widely expressed; lower levels in brain and
CC lung.
CC -!- PTM: S-nitrosylated by GAPDH. In neurons, S-Nitrosylation at Cys-
CC 262 and Cys-274 does not affect the enzyme activity but abolishes
CC chromatin-binding, leading to increases acetylation of histones
CC and activate genes that are associated with neuronal development.
CC In embryonic cortical neurons, S-Nitrosylation regulates dendritic
CC growth and branching. S-Nitrosylation interferes with its
CC interaction with MTA1 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH31055.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC Sequence=BAG59420.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HDAC2ID40803ch6q22.html";
CC -----------------------------------------------------------------------
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DR EMBL; U31814; AAC50814.1; -; mRNA.
DR EMBL; AK092156; BAG52487.1; -; mRNA.
DR EMBL; AK296856; BAG59420.1; ALT_INIT; mRNA.
DR EMBL; AL590398; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL671967; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FO393415; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48252.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48253.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48254.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW48255.1; -; Genomic_DNA.
DR EMBL; BC031055; AAH31055.2; ALT_INIT; mRNA.
DR CCDS; CCDS43493.2; -. [Q92769-1]
DR RefSeq; NP_001518.3; NM_001527.3. [Q92769-1]
DR RefSeq; XP_011534090.1; XM_011535788.1. [Q92769-3]
DR UniGene; Hs.3352; -.
DR PDB; 3MAX; X-ray; 2.05 A; A/B/C=9-374.
DR PDB; 4LXZ; X-ray; 1.85 A; A/B/C=8-376.
DR PDB; 4LY1; X-ray; 1.57 A; A/B/C=8-376.
DR PDBsum; 3MAX; -.
DR PDBsum; 4LXZ; -.
DR PDBsum; 4LY1; -.
DR ProteinModelPortal; Q92769; -.
DR SMR; Q92769; 9-376.
DR BioGrid; 109316; 293.
DR DIP; DIP-24220N; -.
DR IntAct; Q92769; 112.
DR MINT; MINT-90593; -.
DR STRING; 9606.ENSP00000430432; -.
DR BindingDB; Q92769; -.
DR ChEMBL; CHEMBL2093865; -.
DR DrugBank; DB01223; Aminophylline.
DR DrugBank; DB00227; Lovastatin.
DR DrugBank; DB01303; Oxtriphylline.
DR DrugBank; DB00277; Theophylline.
DR DrugBank; DB00313; Valproic Acid.
DR DrugBank; DB02546; Vorinostat.
DR GuidetoPHARMACOLOGY; 2616; -.
DR PhosphoSite; Q92769; -.
DR BioMuta; HDAC2; -.
DR DMDM; 68068066; -.
DR MaxQB; Q92769; -.
DR PaxDb; Q92769; -.
DR PRIDE; Q92769; -.
DR DNASU; 3066; -.
DR Ensembl; ENST00000368632; ENSP00000357621; ENSG00000196591. [Q92769-3]
DR Ensembl; ENST00000519065; ENSP00000430432; ENSG00000196591. [Q92769-1]
DR Ensembl; ENST00000519108; ENSP00000430008; ENSG00000196591. [Q92769-3]
DR GeneID; 3066; -.
DR KEGG; hsa:3066; -.
DR UCSC; uc003pwc.2; human. [Q92769-1]
DR CTD; 3066; -.
DR GeneCards; HDAC2; -.
DR HGNC; HGNC:4853; HDAC2.
DR HPA; CAB005054; -.
DR HPA; HPA011727; -.
DR MIM; 605164; gene.
DR neXtProt; NX_Q92769; -.
DR PharmGKB; PA29227; -.
DR eggNOG; KOG1342; Eukaryota.
DR eggNOG; COG0123; LUCA.
DR GeneTree; ENSGT00530000062889; -.
DR HOGENOM; HOG000225180; -.
DR HOVERGEN; HBG057112; -.
DR InParanoid; Q92769; -.
DR KO; K06067; -.
DR OMA; ACPSPRD; -.
DR PhylomeDB; Q92769; -.
DR TreeFam; TF106171; -.
DR BRENDA; 3.5.1.98; 2681.
DR Reactome; R-HSA-193670; p75NTR negatively regulates cell cycle via SC1.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SABIO-RK; Q92769; -.
DR ChiTaRS; HDAC2; human.
DR EvolutionaryTrace; Q92769; -.
DR GeneWiki; Histone_deacetylase_2; -.
DR GenomeRNAi; 3066; -.
DR NextBio; 12129; -.
DR PRO; PR:Q92769; -.
DR Proteomes; UP000005640; Chromosome 6.
DR Bgee; Q92769; -.
DR CleanEx; HS_HDAC2; -.
DR ExpressionAtlas; Q92769; baseline and differential.
DR Genevisible; Q92769; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0035098; C:ESC/E(Z) complex; IDA:UniProtKB.
DR GO; GO:0000790; C:nuclear chromatin; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016581; C:NuRD complex; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0016580; C:Sin3 complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0001047; F:core promoter binding; IEA:Ensembl.
DR GO; GO:0019213; F:deacetylase activity; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL.
DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB.
DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB.
DR GO; GO:0033558; F:protein deacetylase activity; IMP:BHF-UCL.
DR GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0043044; P:ATP-dependent chromatin remodeling; IDA:UniProtKB.
DR GO; GO:0048149; P:behavioral response to ethanol; IEA:Ensembl.
DR GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR GO; GO:0003300; P:cardiac muscle hypertrophy; IEA:Ensembl.
DR GO; GO:1903351; P:cellular response to dopamine; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; TAS:Reactome.
DR GO; GO:0006338; P:chromatin remodeling; IC:BHF-UCL.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0016358; P:dendrite development; ISS:UniProtKB.
DR GO; GO:0042733; P:embryonic digit morphogenesis; ISS:BHF-UCL.
DR GO; GO:0009913; P:epidermal cell differentiation; ISS:BHF-UCL.
DR GO; GO:0061029; P:eyelid development in camera-type eye; ISS:BHF-UCL.
DR GO; GO:0061198; P:fungiform papilla formation; ISS:BHF-UCL.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0060789; P:hair follicle placode formation; ISS:BHF-UCL.
DR GO; GO:0016575; P:histone deacetylation; IMP:BHF-UCL.
DR GO; GO:0070932; P:histone H3 deacetylation; ISS:UniProtKB.
DR GO; GO:0070933; P:histone H4 deacetylation; ISS:UniProtKB.
DR GO; GO:0006344; P:maintenance of chromatin silencing; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL.
DR GO; GO:0045786; P:negative regulation of cell cycle; TAS:Reactome.
DR GO; GO:0061000; P:negative regulation of dendritic spine development; IEA:Ensembl.
DR GO; GO:0043392; P:negative regulation of DNA binding; IEA:Ensembl.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; TAS:Reactome.
DR GO; GO:0045347; P:negative regulation of MHC class II biosynthetic process; IC:BHF-UCL.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:BHF-UCL.
DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IC:BHF-UCL.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0045862; P:positive regulation of proteolysis; IMP:BHF-UCL.
DR GO; GO:0010870; P:positive regulation of receptor biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IC:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IEA:Ensembl.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; TAS:Reactome.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0031000; P:response to caffeine; IEA:Ensembl.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR003084; His_deacetylse_1.
DR InterPro; IPR023801; His_deacetylse_dom.
DR PANTHER; PTHR10625; PTHR10625; 1.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PIRSF; PIRSF037913; His_deacetylse_1; 1.
DR PRINTS; PR01270; HDASUPER.
DR PRINTS; PR01271; HISDACETLASE.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Chromatin regulator; Complete proteome; Cytoplasm; Hydrolase;
KW Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repressor; S-nitrosylation; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 488 Histone deacetylase 2.
FT /FTId=PRO_0000114693.
FT REGION 9 322 Histone deacetylase.
FT COMPBIAS 300 303 Poly-Gly.
FT ACT_SITE 142 142 {ECO:0000250}.
FT MOD_RES 262 262 S-nitrosocysteine.
FT {ECO:0000250|UniProtKB:P70288}.
FT MOD_RES 274 274 S-nitrosocysteine.
FT {ECO:0000250|UniProtKB:P70288}.
FT MOD_RES 394 394 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:18691976,
FT ECO:0000244|PubMed:19690332,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:24275569}.
FT MOD_RES 422 422 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:19690332,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:24275569}.
FT MOD_RES 424 424 Phosphoserine.
FT {ECO:0000244|PubMed:17081983,
FT ECO:0000244|PubMed:20068231,
FT ECO:0000244|PubMed:21406692,
FT ECO:0000244|PubMed:24275569}.
FT CROSSLNK 462 462 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT VAR_SEQ 1 30 Missing (in isoform 2).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_056175.
FT VARIANT 230 230 R -> C (in dbSNP:rs1042903).
FT {ECO:0000269|PubMed:8917507}.
FT /FTId=VAR_025311.
FT VARIANT 315 315 Y -> H (in dbSNP:rs17852888).
FT {ECO:0000269|PubMed:15489334}.
FT /FTId=VAR_025312.
FT CONFLICT 93 94 QR -> HI (in Ref. 1; AAC50814).
FT {ECO:0000305}.
FT CONFLICT 103 103 V -> A (in Ref. 1; AAC50814).
FT {ECO:0000305}.
FT CONFLICT 146 146 S -> Y (in Ref. 1; AAC50814).
FT {ECO:0000305}.
FT CONFLICT 248 248 K -> M (in Ref. 2; BAG59420).
FT {ECO:0000305}.
FT CONFLICT 281 281 G -> D (in Ref. 2; BAG59420).
FT {ECO:0000305}.
FT STRAND 12 15 {ECO:0000244|PDB:4LY1}.
FT HELIX 20 22 {ECO:0000244|PDB:4LY1}.
FT HELIX 34 45 {ECO:0000244|PDB:4LY1}.
FT HELIX 48 51 {ECO:0000244|PDB:4LY1}.
FT STRAND 52 55 {ECO:0000244|PDB:4LY1}.
FT HELIX 62 65 {ECO:0000244|PDB:4LY1}.
FT TURN 66 68 {ECO:0000244|PDB:4LY1}.
FT HELIX 71 79 {ECO:0000244|PDB:4LY1}.
FT TURN 82 84 {ECO:0000244|PDB:4LY1}.
FT HELIX 85 88 {ECO:0000244|PDB:4LY1}.
FT HELIX 89 95 {ECO:0000244|PDB:4LY1}.
FT STRAND 98 101 {ECO:0000244|PDB:4LY1}.
FT HELIX 107 126 {ECO:0000244|PDB:4LY1}.
FT STRAND 131 135 {ECO:0000244|PDB:4LY1}.
FT HELIX 156 164 {ECO:0000244|PDB:4LY1}.
FT TURN 165 167 {ECO:0000244|PDB:4LY1}.
FT STRAND 171 175 {ECO:0000244|PDB:4LY1}.
FT STRAND 177 179 {ECO:0000244|PDB:4LY1}.
FT HELIX 182 187 {ECO:0000244|PDB:4LY1}.
FT TURN 188 190 {ECO:0000244|PDB:4LY1}.
FT STRAND 192 201 {ECO:0000244|PDB:4LY1}.
FT HELIX 218 220 {ECO:0000244|PDB:4LY1}.
FT STRAND 224 229 {ECO:0000244|PDB:4LY1}.
FT HELIX 235 253 {ECO:0000244|PDB:4LY1}.
FT STRAND 256 261 {ECO:0000244|PDB:4LY1}.
FT HELIX 264 266 {ECO:0000244|PDB:4LY1}.
FT HELIX 279 291 {ECO:0000244|PDB:4LY1}.
FT STRAND 296 299 {ECO:0000244|PDB:4LY1}.
FT HELIX 306 320 {ECO:0000244|PDB:4LY1}.
FT HELIX 335 338 {ECO:0000244|PDB:4LY1}.
FT TURN 339 341 {ECO:0000244|PDB:4LY1}.
FT STRAND 343 345 {ECO:0000244|PDB:4LY1}.
FT HELIX 357 371 {ECO:0000244|PDB:4LY1}.
SQ SEQUENCE 488 AA; 55364 MW; 775419CCCDAE07FA CRC64;
MAYSQGGGKK KVCYYYDGDI GNYYYGQGHP MKPHRIRMTH NLLLNYGLYR KMEIYRPHKA
TAEEMTKYHS DEYIKFLRSI RPDNMSEYSK QMQRFNVGED CPVFDGLFEF CQLSTGGSVA
GAVKLNRQQT DMAVNWAGGL HHAKKSEASG FCYVNDIVLA ILELLKYHQR VLYIDIDIHH
GDGVEEAFYT TDRVMTVSFH KYGEYFPGTG DLRDIGAGKG KYYAVNFPMR DGIDDESYGQ
IFKPIISKVM EMYQPSAVVL QCGADSLSGD RLGCFNLTVK GHAKCVEVVK TFNLPLLMLG
GGGYTIRNVA RCWTYETAVA LDCEIPNELP YNDYFEYFGP DFKLHISPSN MTNQNTPEYM
EKIKQRLFEN LRMLPHAPGV QMQAIPEDAV HEDSGDEDGE DPDKRISIRA SDKRIACDEE
FSDSEDEGEG GRRNVADHKK GAKKARIEED KKETEDKKTD VKEEDKSKDN SGEKTDTKGT
KSEQLSNP
//
ID HIC1_HUMAN Reviewed; 733 AA.
AC Q14526; D3DTI4;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 5.
DT 11-NOV-2015, entry version 147.
DE RecName: Full=Hypermethylated in cancer 1 protein;
DE Short=Hic-1;
DE AltName: Full=Zinc finger and BTB domain-containing protein 29;
GN Name=HIC1; Synonyms=ZBTB29;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), AND VARIANT GLY-725.
RX PubMed=7585125; DOI=10.1038/nm0695-570;
RA Wales M.M., Biel M.A., el Deiry W., Nelkin B.D., Issa J.-P.,
RA Cavenee W.K., Kuerbitz S.J., Baylin S.B.;
RT "p53 activates expression of HIC-1, a new candidate tumour suppressor
RT gene on 17p13.3.";
RL Nat. Med. 1:570-577(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SELF-ASSOCIATION.
RX PubMed=10611298; DOI=10.1073/pnas.96.26.14831;
RA Deltour S., Guerardel C., Leprince D.;
RT "Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a
RT general mechanism for BTB/POZ transcriptional repressors: the case of
RT HIC-1 and gammaFBP-B.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:14831-14836(1999).
RN [5]
RP ALTERNATIVE SPLICING, INTERACTION WITH HIC2, AND SUBCELLULAR LOCATION.
RX PubMed=11554746; DOI=10.1006/bbrc.2001.5624;
RA Deltour S., Pinte S., Guerardel C., Leprince D.;
RT "Characterization of HRG22, a human homologue of the putative tumor
RT suppressor gene HIC1.";
RL Biochem. Biophys. Res. Commun. 287:427-434(2001).
RN [6]
RP FUNCTION, SELF-ASSOCIATION, AND INTERACTION WITH CTBP1.
RX PubMed=12052894; DOI=10.1128/MCB.22.13.4890-4901.2002;
RA Deltour S., Pinte S., Guerardel C., Wasylyk B., Leprince D.;
RT "The human candidate tumor suppressor gene HIC1 recruits CtBP through
RT a degenerate GLDLSKK motif.";
RL Mol. Cell. Biol. 22:4890-4901(2002).
RN [7]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF CYS-540.
RX PubMed=15231840; DOI=10.1074/jbc.M401610200;
RA Pinte S., Stankovic-Valentin N., Deltour S., Rood B.R., Guerardel C.,
RA Leprince D.;
RT "The tumor suppressor gene HIC1 (hypermethylated in cancer 1) is a
RT sequence-specific transcriptional repressor: definition of its
RT consensus binding sequence and analysis of its DNA binding and
RT repressive properties.";
RL J. Biol. Chem. 279:38313-38324(2004).
RN [8]
RP FUNCTION.
RX PubMed=16269335; DOI=10.1016/j.cell.2005.08.011;
RA Chen W.Y., Wang D.H., Yen R.C., Luo J., Gu W., Baylin S.B.;
RT "Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-
RT dependent DNA-damage responses.";
RL Cell 123:437-448(2005).
RN [9]
RP FUNCTION.
RX PubMed=16690027; DOI=10.1016/j.bbrc.2006.04.052;
RA Briones V.R., Chen S., Riegel A.T., Lechleider R.J.;
RT "Mechanism of fibroblast growth factor-binding protein 1 repression by
RT TGF-beta.";
RL Biochem. Biophys. Res. Commun. 345:595-601(2006).
RN [10]
RP FUNCTION IN WNT SIGNALING, AND INTERACTION WITH TCF7L2.
RX PubMed=16724116; DOI=10.1038/sj.emboj.7601147;
RA Valenta T., Lukas J., Doubravska L., Fafilek B., Korinek V.;
RT "HIC1 attenuates Wnt signaling by recruitment of TCF-4 and beta-
RT catenin to the nuclear bodies.";
RL EMBO J. 25:2326-2337(2006).
RN [11]
RP INTERACTION WITH CTBP1 AND CTBP2, AND MUTAGENESIS OF LEU-244.
RX PubMed=16762039; DOI=10.1111/j.1742-4658.2006.05301.x;
RA Stankovic-Valentin N., Verger A., Deltour-Balerdi S., Quinlan K.G.,
RA Crossley M., Leprince D.;
RT "A L225A substitution in the human tumour suppressor HIC1 abolishes
RT its interaction with the corepressor CtBP.";
RL FEBS J. 273:2879-2890(2006).
RN [12]
RP SUMOYLATION AT LYS-333, ACETYLATION AT LYS-333, AND MUTAGENESIS OF
RP LYS-333; GLU-335 AND PRO-336.
RX PubMed=17283066; DOI=10.1128/MCB.01098-06;
RA Stankovic-Valentin N., Deltour S., Seeler J., Pinte S., Vergoten G.,
RA Guerardel C., Dejean A., Leprince D.;
RT "An acetylation/deacetylation-SUMOylation switch through a
RT phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1
RT regulates transcriptional repression activity.";
RL Mol. Cell. Biol. 27:2661-2675(2007).
RN [13]
RP FUNCTION, AND INTERACTION WITH CTBP1.
RX PubMed=17213307; DOI=10.1073/pnas.0610590104;
RA Zhang Q., Wang S.Y., Fleuriel C., Leprince D., Rocheleau J.V.,
RA Piston D.W., Goodman R.H.;
RT "Metabolic regulation of SIRT1 transcription via a HIC1:CtBP
RT corepressor complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:829-833(2007).
RN [14]
RP FUNCTION.
RX PubMed=18347096; DOI=10.1101/gad.1640908;
RA Briggs K.J., Corcoran-Schwartz I.M., Zhang W., Harcke T.,
RA Devereux W.L., Baylin S.B., Eberhart C.G., Watkins D.N.;
RT "Cooperation between the Hic1 and Ptch1 tumor suppressors in
RT medulloblastoma.";
RL Genes Dev. 22:770-785(2008).
RN [15]
RP ERRATUM.
RA Briggs K.J., Corcoran-Schwartz I.M., Zhang W., Harcke T.,
RA Devereux W.L., Baylin S.B., Eberhart C.G., Watkins D.N.;
RL Genes Dev. 22:1410-1410(2008).
RN [16]
RP FUNCTION, AND INTERACTION WITH ARID1A.
RX PubMed=19486893; DOI=10.1016/j.bbrc.2009.05.115;
RA Van Rechem C., Boulay G., Leprince D.;
RT "HIC1 interacts with a specific subunit of SWI/SNF complexes,
RT ARID1A/BAF250A.";
RL Biochem. Biophys. Res. Commun. 385:586-590(2009).
RN [17]
RP FUNCTION.
RX PubMed=19525223; DOI=10.1074/jbc.M109.022350;
RA Van Rechem C., Rood B.R., Touka M., Pinte S., Jenal M., Guerardel C.,
RA Ramsey K., Monte D., Begue A., Tschan M.P., Stephan D.A., Leprince D.;
RT "Scavenger chemokine (CXC motif) receptor 7 (CXCR7) is a direct target
RT gene of HIC1 (hypermethylated in cancer 1).";
RL J. Biol. Chem. 284:20927-20935(2009).
RN [18]
RP FUNCTION, INTERACTION WITH MTA1 AND MBD3, AND MUTAGENESIS OF LYS-333;
RP GLU-335 AND PRO-336.
RX PubMed=20547755; DOI=10.1128/MCB.00582-09;
RA Van Rechem C., Boulay G., Pinte S., Stankovic-Valentin N.,
RA Guerardel C., Leprince D.;
RT "Differential regulation of HIC1 target genes by CtBP and NuRD, via an
RT acetylation/SUMOylation switch, in quiescent versus proliferating
RT cells.";
RL Mol. Cell. Biol. 30:4045-4059(2010).
RN [19]
RP FUNCTION.
RX PubMed=20154726; DOI=10.1038/onc.2010.12;
RA Zhang W., Zeng X., Briggs K.J., Beaty R., Simons B., Chiu Yen R.W.,
RA Tyler M.A., Tsai H.C., Ye Y., Gesell G.S., Herman J.G., Baylin S.B.,
RA Watkins D.N.;
RT "A potential tumor suppressor role for Hic1 in breast cancer through
RT transcriptional repression of ephrin-A1.";
RL Oncogene 29:2467-2476(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237; SER-248 AND
RP SER-366, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Transcriptional repressor. Recognizes and binds to the
CC consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3'. May act as a tumor
CC suppressor. May be involved in development of head, face, limbs
CC and ventral body wall. Involved in down-regulation of SIRT1 and
CC thereby is involved in regulation of p53/TP53-dependent apoptotic
CC DNA-damage responses. The specific target gene promoter
CC association seems to be depend on corepressors, such as CTBP1 or
CC CTBP2 and MTA1. The regulation of SIRT1 transcription in response
CC to nutrient deprivation seems to involve CTBP1. In cooperation
CC with MTA1 (indicative for an association with the NuRD complex)
CC represses transcription from CCND1/cyclin-D1 and CDKN1C/p57Kip2
CC specifically in quiescent cells. Involved in regulation of the Wnt
CC signaling pathway probably by association with TCF7L2 and
CC preventing TCF7L2 and CTNNB1 association with promoters of TCF-
CC responsive genes. Seems to repress transcription from E2F1 and
CC ATOH1 which involves ARID1A, indicative for the participation of a
CC distinct SWI/SNF-type chromatin-remodeling complex. Probably
CC represses transcription from ACKR3, FGFBP1 and EFNA1.
CC {ECO:0000269|PubMed:12052894, ECO:0000269|PubMed:15231840,
CC ECO:0000269|PubMed:16269335, ECO:0000269|PubMed:16690027,
CC ECO:0000269|PubMed:16724116, ECO:0000269|PubMed:17213307,
CC ECO:0000269|PubMed:18347096, ECO:0000269|PubMed:19486893,
CC ECO:0000269|PubMed:19525223, ECO:0000269|PubMed:20154726,
CC ECO:0000269|PubMed:20547755}.
CC -!- SUBUNIT: Self-associates. Interacts with HIC2. Interacts with
CC CTBP1 and CTBP2. Interacts with TCF7L2 and ARID1A. Interacts with
CC MTA1 and MBD3; indicative for an association with the NuRD
CC complex. {ECO:0000269|PubMed:11554746,
CC ECO:0000269|PubMed:12052894, ECO:0000269|PubMed:16724116,
CC ECO:0000269|PubMed:16762039, ECO:0000269|PubMed:17213307,
CC ECO:0000269|PubMed:19486893, ECO:0000269|PubMed:20547755}.
CC -!- INTERACTION:
CC O14497:ARID1A; NbExp=2; IntAct=EBI-2507362, EBI-637887;
CC Q13363:CTBP1; NbExp=4; IntAct=EBI-2507362, EBI-908846;
CC O88712:Ctbp1 (xeno); NbExp=10; IntAct=EBI-2507362, EBI-604547;
CC P56545:CTBP2; NbExp=2; IntAct=EBI-2507362, EBI-741533;
CC P56546:Ctbp2 (xeno); NbExp=2; IntAct=EBI-2507362, EBI-1384883;
CC Q9NQB0:TCF7L2; NbExp=6; IntAct=EBI-2507362, EBI-924724;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11554746}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q14526-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14526-2; Sequence=VSP_006826;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels
CC found in lung, colon, prostate, thymus, testis and ovary.
CC Expression is absent or decreased in many tumor cells.
CC -!- DOMAIN: The BTB domain inhibits the binding to a single consensus
CC binding site, but mediates cooperative binding to multiple binding
CC sites.
CC -!- PTM: Acetylated on several residues, including Lys-333. Lys-333 is
CC deacetylated by SIRT1. {ECO:0000269|PubMed:17283066}.
CC -!- PTM: Sumoylated on Lys-333 by a PIAS family member, which enhances
CC interaction with MTA1, positively regulates transcriptional
CC repression activity and is enhanced by HDAC4.
CC {ECO:0000269|PubMed:17283066}.
CC -!- MISCELLANEOUS: The HIC1 gene is frequently found epigenetically
CC silenced or deleted in different types of solid tumors.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. Hic subfamily. {ECO:0000305}.
CC -!- SIMILARITY: Contains 1 BTB (POZ) domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00037}.
CC -!- SIMILARITY: Contains 5 C2H2-type zinc fingers.
CC {ECO:0000255|PROSITE-ProRule:PRU00042}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HIC1ID40819ch17p13.html";
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DR EMBL; L41919; AAD09201.1; -; Genomic_DNA.
DR EMBL; AC090617; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90562.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90563.1; -; Genomic_DNA.
DR CCDS; CCDS42229.1; -. [Q14526-1]
DR CCDS; CCDS42230.1; -. [Q14526-2]
DR RefSeq; NP_001091672.1; NM_001098202.1. [Q14526-1]
DR RefSeq; NP_006488.2; NM_006497.3. [Q14526-2]
DR UniGene; Hs.695682; -.
DR UniGene; Hs.72956; -.
DR ProteinModelPortal; Q14526; -.
DR SMR; Q14526; 25-145, 429-613.
DR BioGrid; 109337; 26.
DR IntAct; Q14526; 11.
DR MINT; MINT-2730619; -.
DR STRING; 9606.ENSP00000314080; -.
DR PhosphoSite; Q14526; -.
DR BioMuta; HIC1; -.
DR DMDM; 296439502; -.
DR PaxDb; Q14526; -.
DR PRIDE; Q14526; -.
DR DNASU; 3090; -.
DR Ensembl; ENST00000322941; ENSP00000314080; ENSG00000177374. [Q14526-1]
DR Ensembl; ENST00000399849; ENSP00000382742; ENSG00000177374. [Q14526-2]
DR Ensembl; ENST00000619757; ENSP00000477858; ENSG00000177374. [Q14526-2]
DR GeneID; 3090; -.
DR KEGG; hsa:3090; -.
DR UCSC; uc002fty.4; human. [Q14526-1]
DR CTD; 3090; -.
DR GeneCards; HIC1; -.
DR H-InvDB; HIX0039113; -.
DR HGNC; HGNC:4909; HIC1.
DR HPA; HPA043372; -.
DR MIM; 603825; gene.
DR neXtProt; NX_Q14526; -.
DR Orphanet; 531; Miller-Dieker syndrome.
DR PharmGKB; PA29282; -.
DR eggNOG; KOG1721; Eukaryota.
DR eggNOG; COG5048; LUCA.
DR GeneTree; ENSGT00800000124025; -.
DR HOGENOM; HOG000026793; -.
DR HOVERGEN; HBG031606; -.
DR InParanoid; Q14526; -.
DR OMA; PPDPFRG; -.
DR OrthoDB; EOG74J97F; -.
DR PhylomeDB; Q14526; -.
DR TreeFam; TF333488; -.
DR SignaLink; Q14526; -.
DR GeneWiki; HIC1; -.
DR GenomeRNAi; 3090; -.
DR NextBio; 12259; -.
DR PRO; PR:Q14526; -.
DR Proteomes; UP000005640; Chromosome 17.
DR Bgee; Q14526; -.
DR CleanEx; HS_HIC1; -.
DR ExpressionAtlas; Q14526; baseline and differential.
DR Genevisible; Q14526; HS.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 3.30.160.60; -; 4.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR028424; HIC1.
DR InterPro; IPR011333; POZ_dom.
DR InterPro; IPR007087; Znf_C2H2.
DR InterPro; IPR015880; Znf_C2H2-like.
DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR PANTHER; PTHR24409:SF69; PTHR24409:SF69; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF00096; zf-C2H2; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00355; ZnF_C2H2; 5.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome;
KW Developmental protein; DNA-binding; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Tumor suppressor;
KW Ubl conjugation; Wnt signaling pathway; Zinc; Zinc-finger.
FT CHAIN 1 733 Hypermethylated in cancer 1 protein.
FT /FTId=PRO_0000046942.
FT DOMAIN 47 110 BTB. {ECO:0000255|PROSITE-
FT ProRule:PRU00037}.
FT ZN_FING 439 459 C2H2-type 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 509 529 C2H2-type 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 537 557 C2H2-type 3. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 565 585 C2H2-type 4. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 593 613 C2H2-type 5. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT REGION 154 315 Mediates HDAC-dependent transcriptional
FT repression.
FT REGION 241 247 Interaction with CTBP1.
FT COMPBIAS 110 119 Poly-Ala.
FT COMPBIAS 160 167 Poly-Gly.
FT COMPBIAS 195 199 Poly-Pro.
FT MOD_RES 237 237 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 248 248 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 333 333 N6-acetyllysine; alternate.
FT {ECO:0000269|PubMed:17283066}.
FT MOD_RES 366 366 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 704 704 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q9R1Y5}.
FT CROSSLNK 333 333 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO);
FT alternate.
FT VAR_SEQ 1 19 Missing (in isoform 2). {ECO:0000305}.
FT /FTId=VSP_006826.
FT VARIANT 725 725 R -> G (in dbSNP:rs1063317).
FT {ECO:0000269|PubMed:7585125}.
FT /FTId=VAR_063109.
FT MUTAGEN 244 244 L->A: Abolishes interaction with CTBP1
FT and CTBP2. Impairs transcriptional
FT repression.
FT {ECO:0000269|PubMed:16762039}.
FT MUTAGEN 333 333 K->Q: Mimicks acetylation. Impairs
FT interaction with RBBP4 and MTA1 and no
FT effect on interaction with CTBP2. Reduces
FT transcriptional repression.
FT {ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755}.
FT MUTAGEN 333 333 K->R: Abolishes sumoylation; impairs
FT transcriptional repression activity.
FT {ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755}.
FT MUTAGEN 335 335 E->A: Impairs transcriptional repression
FT activity. Decreases interaction with
FT MTA1. {ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755}.
FT MUTAGEN 336 336 P->A: Impairs K-333 acetylation; no
FT effect on sumoylation. Decreases
FT interaction with MTA1.
FT {ECO:0000269|PubMed:17283066,
FT ECO:0000269|PubMed:20547755}.
FT MUTAGEN 540 540 C->S: Abolishes repression activity.
FT {ECO:0000269|PubMed:15231840}.
FT CONFLICT 190 190 P -> R (in Ref. 1; AAD09201).
FT {ECO:0000305}.
SQ SEQUENCE 733 AA; 76508 MW; 6DDD0F49C4E490D3 CRC64;
MTFPEADILL KSGECAGQTM LDTMEAPGHS RQLLLQLNNQ RTKGFLCDVI IVVQNALFRA
HKNVLAASSA YLKSLVVHDN LLNLDHDMVS PAVFRLVLDF IYTGRLADGA EAAAAAAVAP
GAEPSLGAVL AAASYLQIPD LVALCKKRLK RHGKYCHLRG GGGGGGGYAP YGRPGRGLRA
ATPVIQACYP SPVGPPPPPA AEPPSGPEAA VNTHCAELYA SGPGPAAALC ASERRCSPLC
GLDLSKKSPP GSAAPERPLA ERELPPRPDS PPSAGPAAYK EPPLALPSLP PLPFQKLEEA
APPSDPFRGG SGSPGPEPPG RPDGPSLLYR WMKHEPGLGS YGDELGRERG SPSERCEERG
GDAAVSPGGP PLGLAPPPRY PGSLDGPGAG GDGDDYKSSS EETGSSEDPS PPGGHLEGYP
CPHLAYGEPE SFGDNLYVCI PCGKGFPSSE QLNAHVEAHV EEEEALYGRA EAAEVAAGAA
GLGPPFGGGG DKVAGAPGGL GELLRPYRCA SCDKSYKDPA TLRQHEKTHW LTRPYPCTIC
GKKFTQRGTM TRHMRSHLGL KPFACDACGM RFTRQYRLTE HMRIHSGEKP YECQVCGGKF
AQQRNLISHM KMHAVGGAAG AAGALAGLGG LPGVPGPDGK GKLDFPEGVF AVARLTAEQL
SLKQQDKAAA AELLAQTTHF LHDPKVALES LYPLAKFTAE LGLSPDKAAE VLSQGAHLAA
GPDGRTIDRF SPT
//
ID IKZF1_HUMAN Reviewed; 519 AA.
AC Q13422; A4D260; B4E0Z1; D3DVM5; O00598; Q53XL2; Q69BM4; Q8WVA3;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 11-NOV-2015, entry version 150.
DE RecName: Full=DNA-binding protein Ikaros;
DE AltName: Full=Ikaros family zinc finger protein 1;
DE AltName: Full=Lymphoid transcription factor LyF-1;
GN Name=IKZF1; Synonyms=IK1, IKAROS, LYF1, ZNFN1A1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Bone marrow;
RX PubMed=8964602; DOI=10.1016/0165-2478(95)02479-4;
RA Nietfeld W., Meyerhans A.;
RT "Cloning and sequencing of hIk-1, a cDNA encoding a human homologue of
RT mouse Ikaros/LyF-1.";
RL Immunol. Lett. 49:139-141(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RX PubMed=8543809;
RA Molnar A., Wu P., Largespada D.A., Vortkamp A., Scherer S.,
RA Copeland N.G., Jenkins N.A., Bruns G., Georgopoulos K.;
RT "The Ikaros gene encodes a family of lymphocyte-restricted zinc finger
RT DNA binding proteins, highly conserved in human and mouse.";
RL J. Immunol. 156:585-592(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IKX).
RA Sanchez-Tapia E.M., Rodriguez R.E., Gonzalez-Sarmiento R.;
RT "Molecular misreading is involved in generation of Ikaros diversity.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK7).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK7).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP IDENTIFICATION IN THE NURD COMPLEX, IDENTIFICATION IN THE BAF COMPLEX,
RP INTERACTION WITH SMARCA4 AND CHD4, AND FUNCTION.
RX PubMed=10204490; DOI=10.1016/S1074-7613(00)80034-5;
RA Kim J., Sif S., Jones B., Jackson A., Koipally J., Heller E.,
RA Winandy S., Viel A., Sawyer A., Ikeda T., Kingston R.,
RA Georgopoulos K.;
RT "Ikaros DNA-binding proteins direct formation of chromatin remodeling
RT complexes in lymphocytes.";
RL Immunity 10:345-355(1999).
RN [11]
RP INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, AND CHROMOSOMAL
RP TRANSLOCATION WITH BCL6.
RX PubMed=10753856;
RA Hosokawa Y., Maeda Y., Ichinohasama R., Miura I., Taniwaki M.,
RA Seto M.;
RT "The Ikaros gene, a central regulator of lymphoid differentiation,
RT fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in
RT a patient with diffuse large B-cell lymphoma.";
RL Blood 95:2719-2721(2000).
RN [12]
RP INTERACTION WITH IKZF4 AND IKZF5.
RX PubMed=10978333; DOI=10.1074/jbc.M005457200;
RA Perdomo J., Holmes M., Chong B., Crossley M.;
RT "Eos and pegasus, two members of the Ikaros family of proteins with
RT distinct DNA binding activities.";
RL J. Biol. Chem. 275:38347-38354(2000).
RN [13]
RP FUNCTION, ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=17135265; DOI=10.1074/jbc.M605627200;
RA Ronni T., Payne K.J., Ho S., Bradley M.N., Dorsam G., Dovat S.;
RT "Human Ikaros function in activated T cells is regulated by
RT coordinated expression of its largest isoforms.";
RL J. Biol. Chem. 282:2538-2547(2007).
RN [14]
RP FUNCTION, AND ALTERNATIVE SPLICING.
RX PubMed=17934067; DOI=10.1182/blood-2007-07-098202;
RA Dijon M., Bardin F., Murati A., Batoz M., Chabannon C., Tonnelle C.;
RT "The role of Ikaros in human erythroid differentiation.";
RL Blood 111:1138-1146(2008).
RN [15]
RP FUNCTION IN GAMMA SATELLITE DNA BINDING.
RX PubMed=19141594; DOI=10.1101/gr.086496.108;
RA Kim J.-H., Ebersole T., Kouprina N., Noskov V.N., Ohzeki J.-I.,
RA Masumoto H., Mravinac B., Sullivan B.A., Pavlicek A., Dovat S.,
RA Pack S.D., Kwon Y.-W., Flanagan P.T., Loukinov D., Lobanenkov V.,
RA Larionov V.;
RT "Human gamma-satellite DNA maintains open chromatin structure and
RT protects a transgene from epigenetic silencing.";
RL Genome Res. 19:533-544(2009).
RN [16]
RP INVOLVEMENT IN ACUTE LYMPHOBLASIC LEUKEMIA.
RX PubMed=19129520; DOI=10.1056/NEJMoa0808253;
RA Mullighan C.G., Su X., Zhang J., Radtke I., Phillips L.A.,
RA Miller C.B., Ma J., Liu W., Cheng C., Schulman B.A., Harvey R.C.,
RA Chen I.-M., Clifford R.J., Carroll W.L., Reaman G., Bowman W.P.,
RA Devidas M., Gerhard D.S., Yang W., Relling M.V., Shurtleff S.A.,
RA Campana D., Borowitz M.J., Pui C.H., Smith M., Hunger S.P.,
RA Willman C.L., Downing J.R.;
RT "Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.";
RL N. Engl. J. Med. 360:470-480(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63; SER-258; SER-361 AND
RP SER-364, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP FUNCTION IN DNA BINDING, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND
RP ALTERNATIVE SPLICING.
RX PubMed=22106042; DOI=10.1002/pbc.23406;
RA Li Z., Song C., Ouyang H., Lai L., Payne K.J., Dovat S.;
RT "Cell cycle-specific function of Ikaros in human leukemia.";
RL Pediatr. Blood Cancer 59:69-76(2012).
RN [20]
RP PHOSPHORYLATION AT SER-361 AND SER-364 BY SYK, AND SUBCELLULAR
RP LOCATION.
RX PubMed=23071339; DOI=10.1073/pnas.1209828109;
RA Uckun F.M., Ma H., Zhang J., Ozer Z., Dovat S., Mao C., Ishkhanian R.,
RA Goodman P., Qazi S.;
RT "Serine phosphorylation by SYK is critical for nuclear localization
RT and transcription factor function of Ikaros.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:18072-18077(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Transcription regulator of hematopoietic cell
CC differentiation (PubMed:17934067). Binds gamma-satellite DNA
CC (PubMed:17135265, PubMed:19141594). Plays a role in the
CC development of lymphocytes, B- and T-cells. Binds and activates
CC the enhancer (delta-A element) of the CD3-delta gene. Repressor of
CC the TDT (fikzfterminal deoxynucleotidyltransferase) gene during
CC thymocyte differentiation. Regulates transcription through
CC association with both HDAC-dependent and HDAC-independent
CC complexes. Targets the 2 chromatin-remodeling complexes, NuRD and
CC BAF (SWI/SNF), in a single complex (PYR complex), to the beta-
CC globin locus in adult erythrocytes. Increases normal apoptosis in
CC adult erythroid cells. Confers early temporal competence to
CC retinal progenitor cells (RPCs) (By similarity). Function is
CC isoform-specific and is modulated by dominant-negative inactive
CC isoforms (PubMed:17135265, PubMed:17934067).
CC {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490,
CC ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067,
CC ECO:0000269|PubMed:19141594}.
CC -!- SUBUNIT: Heterodimer formed by the various isoforms; this
CC modulates transcription regulator activity (PubMed:17135265,
CC PubMed:17934067). Heterodimer with other IKAROS family members.
CC Interacts with IKZF4 AND IKZF5 (PubMed:10978333). Component of the
CC chromatin-remodeling NuRD repressor complex which includes at
CC least HDAC1, HDAC2, RBBP4, RBBP7, IKZF1, MTA2, MBD2, MBD3, MTA1L1,
CC CHD3 and CHD4. Interacts directly with the CHD4 component of the
CC NuRD complex. Component of the BAF (SWI/SNF) gene activator
CC complex which includes ACTB, ARID1A, ARID1B, IKZF1, ARID1A,
CC ARID1B, SMARCA2, SMARCA4 and at least one BAF subunit. Interacts
CC directly with the SMARCA4 component of the BAF complex (By
CC similarity). Interacts with SUMO1; the interaction sumoylates
CC IKAROS, promoted by PIAS2 and PIAS3. Interacts with PIAS2 (isoform
CC alpha); the interaction promotes sumoylation and reduces
CC transcription repression. Interacts, to a lesser extent, with
CC PIAS3. Interacts with PPP1CC; the interaction targets PPP1CC to
CC pericentromeric heterochromatin, dephosphorylates IKAROS,
CC stabilizes it and prevents it from degradation. Interacts with
CC IKZF3 (By similarity). {ECO:0000250, ECO:0000269|PubMed:10204490,
CC ECO:0000269|PubMed:10978333, ECO:0000305|PubMed:17135265,
CC ECO:0000305|PubMed:17934067}.
CC -!- INTERACTION:
CC A8K932:-; NbExp=3; IntAct=EBI-745305, EBI-10174671;
CC Q8WTP8:AEN; NbExp=3; IntAct=EBI-745305, EBI-8637627;
CC Q96Q83:ALKBH3; NbExp=3; IntAct=EBI-745305, EBI-6658697;
CC Q9BXS5:AP1M1; NbExp=3; IntAct=EBI-745305, EBI-541426;
CC Q9H6L4:ARMC7; NbExp=3; IntAct=EBI-745305, EBI-742909;
CC Q13895:BYSL; NbExp=5; IntAct=EBI-745305, EBI-358049;
CC Q9NUL5:C19orf66; NbExp=3; IntAct=EBI-745305, EBI-10313866;
CC Q9NX04:C1orf109; NbExp=3; IntAct=EBI-745305, EBI-8643161;
CC Q8IYL3:C1orf174; NbExp=3; IntAct=EBI-745305, EBI-715898;
CC Q9H7E9:C8orf33; NbExp=3; IntAct=EBI-745305, EBI-715389;
CC Q9HC52:CBX8; NbExp=3; IntAct=EBI-745305, EBI-712912;
CC Q8IYX8-2:CEP57L1; NbExp=3; IntAct=EBI-745305, EBI-10181988;
CC P61024:CKS1B; NbExp=3; IntAct=EBI-745305, EBI-456371;
CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-745305, EBI-10171858;
CC P56545:CTBP2; NbExp=5; IntAct=EBI-745305, EBI-741533;
CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-745305, EBI-10171902;
CC O43602:DCX; NbExp=4; IntAct=EBI-745305, EBI-8646694;
CC P26196:DDX6; NbExp=3; IntAct=EBI-745305, EBI-351257;
CC Q92630:DYRK2; NbExp=3; IntAct=EBI-745305, EBI-749432;
CC Q3B820:FAM161A; NbExp=3; IntAct=EBI-745305, EBI-719941;
CC Q7L5A3:FAM214B; NbExp=4; IntAct=EBI-745305, EBI-745689;
CC Q9Y247:FAM50B; NbExp=4; IntAct=EBI-745305, EBI-742802;
CC Q5TZK3:FAM74A6; NbExp=3; IntAct=EBI-745305, EBI-10247271;
CC P61328:FGF12; NbExp=3; IntAct=EBI-745305, EBI-6657662;
CC Q96NE9:FRMD6; NbExp=3; IntAct=EBI-745305, EBI-741729;
CC O76003:GLRX3; NbExp=3; IntAct=EBI-745305, EBI-374781;
CC Q8NEA9:GMCL1P1; NbExp=3; IntAct=EBI-745305, EBI-745707;
CC Q9H1K1:ISCU; NbExp=3; IntAct=EBI-745305, EBI-1047335;
CC Q8TAP4:LMO3; NbExp=3; IntAct=EBI-745305, EBI-742259;
CC Q9Y4Z0:LSM4; NbExp=3; IntAct=EBI-745305, EBI-372521;
CC Q9UI95:MAD2L2; NbExp=3; IntAct=EBI-745305, EBI-77889;
CC Q96EZ8:MCRS1; NbExp=3; IntAct=EBI-745305, EBI-348259;
CC Q9UBU8:MORF4L1; NbExp=3; IntAct=EBI-745305, EBI-399246;
CC Q15014:MORF4L2; NbExp=3; IntAct=EBI-745305, EBI-399257;
CC Q13330:MTA1; NbExp=3; IntAct=EBI-745305, EBI-714236;
CC Q9HC98:NEK6; NbExp=3; IntAct=EBI-745305, EBI-740364;
CC Q9BVI4:NOC4L; NbExp=3; IntAct=EBI-745305, EBI-395927;
CC Q13526:PIN1; NbExp=3; IntAct=EBI-745305, EBI-714158;
CC Q96T60:PNKP; NbExp=3; IntAct=EBI-745305, EBI-1045072;
CC O43741:PRKAB2; NbExp=3; IntAct=EBI-745305, EBI-1053424;
CC P25786:PSMA1; NbExp=3; IntAct=EBI-745305, EBI-359352;
CC P25789:PSMA4; NbExp=3; IntAct=EBI-745305, EBI-359310;
CC Q7Z474:PSMA4; NbExp=3; IntAct=EBI-745305, EBI-10257551;
CC O75771:RAD51D; NbExp=4; IntAct=EBI-745305, EBI-1055693;
CC P57060:RWDD2B; NbExp=4; IntAct=EBI-745305, EBI-724442;
CC Q9BWG6:SCNM1; NbExp=3; IntAct=EBI-745305, EBI-748391;
CC O00560:SDCBP; NbExp=3; IntAct=EBI-745305, EBI-727004;
CC Q9H788:SH2D4A; NbExp=3; IntAct=EBI-745305, EBI-747035;
CC P62306:SNRPF; NbExp=3; IntAct=EBI-745305, EBI-356900;
CC Q13573:SNW1; NbExp=3; IntAct=EBI-745305, EBI-632715;
CC Q9H0A9:SPATC1L; NbExp=3; IntAct=EBI-745305, EBI-372911;
CC Q9BSW7:SYT17; NbExp=3; IntAct=EBI-745305, EBI-745392;
CC Q7KZS0:UBE2I; NbExp=3; IntAct=EBI-745305, EBI-10180829;
CC Q15007:WTAP; NbExp=3; IntAct=EBI-745305, EBI-751647;
CC Q96NC0:ZMAT2; NbExp=3; IntAct=EBI-745305, EBI-2682299;
CC Q8TAU3:ZNF417; NbExp=3; IntAct=EBI-745305, EBI-740727;
CC Q9P0T4:ZNF581; NbExp=3; IntAct=EBI-745305, EBI-745520;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17135265,
CC ECO:0000269|PubMed:22106042, ECO:0000269|PubMed:23071339}. Note=In
CC resting lymphocytes, distributed diffusely throughout the nucleus.
CC Localizes to pericentromeric heterochromatin in proliferating
CC cells. This localization requires DNA binding which is regulated
CC by phosphorylation / dephosphorylation events.
CC {ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:22106042}.
CC -!- SUBCELLULAR LOCATION: Isoform Ik2: Nucleus. Note=In resting
CC lymphocytes, distributed diffusely throughout the nucleus.
CC Localizes to pericentromeric heterochromatin in proliferating
CC cells. This localization requires DNA binding which is regulated
CC by phosphorylation / dephosphorylation events (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Isoform Ik6: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=Ik1;
CC IsoId=Q13422-1; Sequence=Displayed;
CC Name=Ik2;
CC IsoId=Q13422-2; Sequence=VSP_006848;
CC Name=Ik3;
CC IsoId=Q13422-3; Sequence=VSP_006850;
CC Name=Ik4;
CC IsoId=Q13422-4; Sequence=VSP_006847, VSP_006850;
CC Name=Ik5;
CC IsoId=Q13422-5; Sequence=VSP_006852;
CC Name=Ik6;
CC IsoId=Q13422-6; Sequence=VSP_006849;
CC Name=Ik7;
CC IsoId=Q13422-7; Sequence=VSP_006851;
CC Name=Ikx;
CC IsoId=Q13422-8; Sequence=VSP_006851, VSP_053404, VSP_053405;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in thymus, spleen and
CC peripheral blood Leukocytes and lymph nodes. Lower expression in
CC bone marrow and small intestine. {ECO:0000269|PubMed:8543809,
CC ECO:0000269|PubMed:8964602}.
CC -!- DOMAIN: The N-terminal zinc-fingers 2 and 3 are required for DNA
CC binding as well as for targeting IKFZ1 to pericentromeric
CC heterochromatin. {ECO:0000250}.
CC -!- DOMAIN: The C-terminal zinc-finger domain is required for
CC dimerization. {ECO:0000250}.
CC -!- PTM: Phosphorylation controls cell-cycle progression from late
CC G(1) stage to S stage. Hyperphosphorylated during G2/M phase.
CC Dephosphorylated state during late G(1) phase. Phosphorylation on
CC Thr-140 is required for DNA and pericentromeric location during
CC mitosis. CK2 is the main kinase, in vitro. GSK3 and CDK may also
CC contribute to phosphorylation of the C-terminal serine and
CC threonine residues. Phosphorylation on these C-terminal residues
CC reduces the DNA-binding ability. Phosphorylation/dephosphorylation
CC events on Ser-13 and Ser-295 regulate TDT expression during
CC thymocyte differentiation. Dephosphorylation by protein
CC phosphatase 1 regulates stability and pericentromeric
CC heterochromatin location. Phosphorylated in both lymphoid and non-
CC lymphoid tissues (By similarity). Phosphorylation at Ser-361 and
CC Ser-364 downstream of SYK induces nuclear translocation.
CC {ECO:0000250, ECO:0000269|PubMed:22106042,
CC ECO:0000269|PubMed:23071339}.
CC -!- PTM: Sumoylated. Simulataneous sumoylation on the 2 sites results
CC in a loss of both HDAC-dependent and HDAC-independent repression.
CC Has no effect on pericentromeric heterochromatin location.
CC Desumoylated by SENP1 (By similarity). {ECO:0000250}.
CC -!- PTM: Polyubiquitinated. {ECO:0000250}.
CC -!- DISEASE: Note=Defects in IKZF1 are frequent occurrences (28.6%) in
CC acute lymphoblasic leukemia (ALL). Such alterations or deletions
CC lead to poor prognosis for ALL.
CC -!- DISEASE: Note=Chromosomal aberrations involving IKZF1 are a cause
CC of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation
CC t(3;7)(q27;p12), with BCL6.
CC -!- SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SIMILARITY: Contains 6 C2H2-type zinc fingers.
CC {ECO:0000255|PROSITE-ProRule:PRU00042}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/IkarosID258.html";
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DR EMBL; U40462; AAC50459.1; -; mRNA.
DR EMBL; S80876; AAB50683.1; -; mRNA.
DR EMBL; AY377974; AAR84585.1; -; mRNA.
DR EMBL; AK303586; BAG64603.1; -; mRNA.
DR EMBL; BT009836; AAP88838.1; -; mRNA.
DR EMBL; AC124014; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC233268; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471128; EAW60977.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW60978.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW60981.1; -; Genomic_DNA.
DR EMBL; CH236955; EAL23900.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW60979.1; -; Genomic_DNA.
DR EMBL; BC018349; AAH18349.1; -; mRNA.
DR CCDS; CCDS59055.1; -. [Q13422-7]
DR CCDS; CCDS69299.1; -. [Q13422-5]
DR CCDS; CCDS75596.1; -. [Q13422-1]
DR CCDS; CCDS75597.1; -. [Q13422-3]
DR CCDS; CCDS78233.1; -. [Q13422-2]
DR RefSeq; NP_001207694.1; NM_001220765.2. [Q13422-7]
DR RefSeq; NP_001207696.1; NM_001220767.2.
DR RefSeq; NP_001207697.1; NM_001220768.2. [Q13422-3]
DR RefSeq; NP_001207699.1; NM_001220770.2.
DR RefSeq; NP_001207700.1; NM_001220771.2. [Q13422-5]
DR RefSeq; NP_001278766.1; NM_001291837.1. [Q13422-7]
DR RefSeq; NP_001278767.1; NM_001291838.1. [Q13422-2]
DR RefSeq; NP_001278768.1; NM_001291839.1.
DR RefSeq; NP_001278769.1; NM_001291840.1. [Q13422-6]
DR RefSeq; NP_001278770.1; NM_001291841.1.
DR RefSeq; NP_001278771.1; NM_001291842.1.
DR RefSeq; NP_001278772.1; NM_001291843.1.
DR RefSeq; NP_001278773.1; NM_001291844.1.
DR RefSeq; NP_006051.1; NM_006060.5. [Q13422-1]
DR RefSeq; XP_011513370.1; XM_011515068.1. [Q13422-1]
DR RefSeq; XP_011513371.1; XM_011515069.1. [Q13422-1]
DR RefSeq; XP_011513377.1; XM_011515075.1. [Q13422-2]
DR RefSeq; XP_011513378.1; XM_011515076.1. [Q13422-2]
DR UniGene; Hs.435949; -.
DR UniGene; Hs.488251; -.
DR UniGene; Hs.646004; -.
DR UniGene; Hs.731495; -.
DR ProteinModelPortal; Q13422; -.
DR SMR; Q13422; 112-220, 460-509.
DR BioGrid; 115604; 118.
DR DIP; DIP-41110N; -.
DR IntAct; Q13422; 68.
DR MINT; MINT-129252; -.
DR STRING; 9606.ENSP00000331614; -.
DR PhosphoSite; Q13422; -.
DR BioMuta; IKZF1; -.
DR DMDM; 3913926; -.
DR MaxQB; Q13422; -.
DR PaxDb; Q13422; -.
DR PRIDE; Q13422; -.
DR DNASU; 10320; -.
DR Ensembl; ENST00000331340; ENSP00000331614; ENSG00000185811. [Q13422-1]
DR Ensembl; ENST00000343574; ENSP00000342750; ENSG00000185811. [Q13422-2]
DR Ensembl; ENST00000349824; ENSP00000342485; ENSG00000185811. [Q13422-5]
DR Ensembl; ENST00000357364; ENSP00000349928; ENSG00000185811. [Q13422-3]
DR Ensembl; ENST00000359197; ENSP00000352123; ENSG00000185811. [Q13422-7]
DR Ensembl; ENST00000438033; ENSP00000396554; ENSG00000185811. [Q13422-2]
DR Ensembl; ENST00000439701; ENSP00000413025; ENSG00000185811. [Q13422-7]
DR GeneID; 10320; -.
DR KEGG; hsa:10320; -.
DR UCSC; uc003tow.4; human. [Q13422-1]
DR UCSC; uc003tox.4; human. [Q13422-7]
DR UCSC; uc003tpa.4; human. [Q13422-6]
DR UCSC; uc011kck.2; human. [Q13422-2]
DR UCSC; uc022acq.1; human. [Q13422-5]
DR UCSC; uc022acs.1; human. [Q13422-4]
DR UCSC; uc022acx.1; human. [Q13422-3]
DR CTD; 10320; -.
DR GeneCards; IKZF1; -.
DR HGNC; HGNC:13176; IKZF1.
DR HPA; CAB009247; -.
DR HPA; HPA035221; -.
DR HPA; HPA035222; -.
DR MIM; 603023; gene.
DR neXtProt; NX_Q13422; -.
DR Orphanet; 317473; Pancytopenia due to IKZF1 mutations.
DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia.
DR PharmGKB; PA37748; -.
DR eggNOG; KOG1721; Eukaryota.
DR eggNOG; COG5048; LUCA.
DR GeneTree; ENSGT00550000074392; -.
DR HOVERGEN; HBG004752; -.
DR InParanoid; Q13422; -.
DR KO; K09220; -.
DR OMA; GDKCLSD; -.
DR PhylomeDB; Q13422; -.
DR TreeFam; TF331189; -.
DR SignaLink; Q13422; -.
DR ChiTaRS; IKZF1; human.
DR GeneWiki; IKZF1; -.
DR GenomeRNAi; 10320; -.
DR NextBio; 39123; -.
DR PRO; PR:Q13422; -.
DR Proteomes; UP000005640; Chromosome 7.
DR Bgee; Q13422; -.
DR CleanEx; HS_IKZF1; -.
DR ExpressionAtlas; Q13422; baseline and differential.
DR Genevisible; Q13422; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005721; C:pericentric heterochromatin; IEA:Ensembl.
DR GO; GO:0043234; C:protein complex; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IBA:GO_Central.
DR GO; GO:0035881; P:amacrine cell differentiation; IEA:Ensembl.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0048535; P:lymph node development; IEA:Ensembl.
DR GO; GO:0030098; P:lymphocyte differentiation; IMP:UniProtKB.
DR GO; GO:0007498; P:mesoderm development; TAS:ProtInc.
DR GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0048541; P:Peyer's patch development; IEA:Ensembl.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0045660; P:positive regulation of neutrophil differentiation; IEA:Ensembl.
DR GO; GO:0051138; P:positive regulation of NK T cell differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GO_Central.
DR GO; GO:0060040; P:retinal bipolar neuron differentiation; IEA:Ensembl.
DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR Gene3D; 3.30.160.60; -; 4.
DR InterPro; IPR007087; Znf_C2H2.
DR InterPro; IPR015880; Znf_C2H2-like.
DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR Pfam; PF00096; zf-C2H2; 1.
DR SMART; SM00355; ZnF_C2H2; 6.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cell cycle; Chromatin regulator;
KW Chromosomal rearrangement; Complete proteome; Cytoplasm;
KW Developmental protein; DNA-binding; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1 519 DNA-binding protein Ikaros.
FT /FTId=PRO_0000047094.
FT ZN_FING 117 139 C2H2-type 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 145 167 C2H2-type 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 173 195 C2H2-type 3. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 201 224 C2H2-type 4. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 462 484 C2H2-type 5. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 490 514 C2H2-type 6. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT REGION 154 163 Required for both high-affinity DNA
FT binding and pericentromeric
FT heterochromatin localization.
FT {ECO:0000250}.
FT REGION 180 195 Required for both high-affinity DNA
FT binding and pericentromeric
FT heterochromatin localization.
FT {ECO:0000250}.
FT REGION 468 471 Required for binding PP1CC.
FT {ECO:0000250}.
FT COMPBIAS 373 376 Poly-Leu.
FT SITE 159 159 Required for both pericentromeric
FT heterochromatin localization and complete
FT DNA binding. {ECO:0000250}.
FT SITE 162 162 Required for both pericentromeric
FT heterochromatin localization and complete
FT DNA binding. {ECO:0000250}.
FT SITE 188 188 Required for both pericentromeric
FT heterochromatin localization and DNA
FT binding. {ECO:0000250}.
FT MOD_RES 13 13 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 23 23 Phosphothreonine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 63 63 Phosphoserine.
FT {ECO:0000244|PubMed:19690332}.
FT MOD_RES 101 101 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 140 140 Phosphothreonine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 168 168 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 196 196 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 258 258 Phosphoserine.
FT {ECO:0000244|PubMed:19690332}.
FT MOD_RES 295 295 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 361 361 Phosphoserine.
FT {ECO:0000244|PubMed:19690332,
FT ECO:0000269|PubMed:23071339}.
FT MOD_RES 364 364 Phosphoserine.
FT {ECO:0000244|PubMed:19690332,
FT ECO:0000269|PubMed:23071339}.
FT MOD_RES 389 389 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 391 391 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 393 393 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 397 397 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 398 398 Phosphothreonine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 402 402 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q03267}.
FT MOD_RES 445 445 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT CROSSLNK 58 58 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT {ECO:0000250}.
FT CROSSLNK 241 241 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT {ECO:0000250}.
FT VAR_SEQ 10 53 Missing (in isoform Ik4). {ECO:0000305}.
FT /FTId=VSP_006847.
FT VAR_SEQ 54 283 Missing (in isoform Ik6). {ECO:0000305}.
FT /FTId=VSP_006849.
FT VAR_SEQ 54 140 Missing (in isoform Ik2).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_006848.
FT VAR_SEQ 141 283 Missing (in isoform Ik5). {ECO:0000305}.
FT /FTId=VSP_006852.
FT VAR_SEQ 197 283 Missing (in isoform Ik3 and isoform Ik4).
FT {ECO:0000305}.
FT /FTId=VSP_006850.
FT VAR_SEQ 197 238 Missing (in isoform Ik7 and isoform Ikx).
FT {ECO:0000303|PubMed:15489334,
FT ECO:0000303|Ref.3, ECO:0000303|Ref.5}.
FT /FTId=VSP_006851.
FT VAR_SEQ 260 268 RSLVLDRLA -> ISRAGQTSK (in isoform Ikx).
FT {ECO:0000303|Ref.3}.
FT /FTId=VSP_053404.
FT VAR_SEQ 269 519 Missing (in isoform Ikx).
FT {ECO:0000303|Ref.3}.
FT /FTId=VSP_053405.
FT CONFLICT 11 12 QV -> FS (in Ref. 2; AAB50683).
FT {ECO:0000305}.
FT CONFLICT 214 214 S -> T (in Ref. 2; AAB50683).
FT {ECO:0000305}.
FT CONFLICT 245 245 N -> K (in Ref. 2; AAB50683).
FT {ECO:0000305}.
FT CONFLICT 296 296 Missing (in Ref. 2; AAB50683).
FT {ECO:0000305}.
FT CONFLICT 298 298 S -> T (in Ref. 2; AAB50683).
FT {ECO:0000305}.
FT CONFLICT 352 355 KPLA -> RRS (in Ref. 2; AAB50683).
FT {ECO:0000305}.
FT CONFLICT 372 372 N -> Y (in Ref. 2; AAB50683).
FT {ECO:0000305}.
FT CONFLICT 420 426 PHARNGL -> RRAQRV (in Ref. 2; AAB50683).
FT {ECO:0000305}.
SQ SEQUENCE 519 AA; 57528 MW; 7B0129C4E3FE41A8 CRC64;
MDADEGQDMS QVSGKESPPV SDTPDEGDEP MPIPEDLSTT SGGQQSSKSD RVVASNVKVE
TQSDEENGRA CEMNGEECAE DLRMLDASGE KMNGSHRDQG SSALSGVGGI RLPNGKLKCD
ICGIICIGPN VLMVHKRSHT GERPFQCNQC GASFTQKGNL LRHIKLHSGE KPFKCHLCNY
ACRRRDALTG HLRTHSVGKP HKCGYCGRSY KQRSSLEEHK ERCHNYLESM GLPGTLYPVI
KEETNHSEMA EDLCKIGSER SLVLDRLASN VAKRKSSMPQ KFLGDKGLSD TPYDSSASYE
KENEMMKSHV MDQAINNAIN YLGAESLRPL VQTPPGGSEV VPVISPMYQL HKPLAEGTPR
SNHSAQDSAV ENLLLLSKAK LVPSEREASP SNSCQDSTDT ESNNEEQRSG LIYLTNHIAP
HARNGLSLKE EHRAYDLLRA ASENSQDALR VVSTSGEQMK VYKCEHCRVL FLDHVMYTIH
MGCHGFRDPF ECNMCGYHSQ DRYEFSSHIT RGEHRFHMS
//
ID ITF2_HUMAN Reviewed; 667 AA.
AC P15884; B3KT62; B3KUC0; B4DT37; B4DUG3; B7Z5M6; B7Z6Y1; G0LNT9;
AC G0LNU0; G0LNU1; G0LNU2; G0LNU4; G0LNU5; G0LNU8; G0LNU9; G0LNV0;
AC G0LNV1; G0LNV2; H3BPQ1; Q08AP2; Q08AP3; Q15439; Q15440; Q15441;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 3.
DT 11-NOV-2015, entry version 171.
DE RecName: Full=Transcription factor 4;
DE Short=TCF-4;
DE AltName: Full=Class B basic helix-loop-helix protein 19;
DE Short=bHLHb19;
DE AltName: Full=Immunoglobulin transcription factor 2;
DE Short=ITF-2;
DE AltName: Full=SL3-3 enhancer factor 2;
DE Short=SEF-2;
GN Name=TCF4; Synonyms=BHLHB19, ITF2, SEF2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SEF2-1A; SEF2-1B AND SEF2-1D),
RP AND ALTERNATIVE SPLICING (ISOFORM SEF2-1C).
RC TISSUE=Thymocyte, and Thymus;
RX PubMed=1681116;
RA Corneliussen B., Thornell A., Hallberg B., Grundstroem T.;
RT "Helix-loop-helix transcriptional activators bind to a sequence in
RT glucocorticoid response elements of retrovirus enhancers.";
RL J. Virol. 65:6084-6093(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A-; B-DELTA; B+DELTA; C-;
RP C-DELTA; D-; E-; F-; G-; H-; I-; SEF2-1A; SEF2-1B AND SEF2-1D), AND
RP ALTERNATIVE SPLICING.
RX PubMed=21789225; DOI=10.1371/journal.pone.0022138;
RA Sepp M., Kannike K., Eesmaa A., Urb M., Timmusk T.;
RT "Functional diversity of human basic helix-loop-helix transcription
RT factor TCF4 isoforms generated by alternative 5' exon usage and
RT splicing.";
RL PLoS ONE 6:E22138-E22138(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SEF2-1A; C-; D-; F-;
RP 11 AND 13).
RC TISSUE=Brain, Hippocampus, Spleen, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D.,
RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S.,
RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R.,
RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T.,
RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E.,
RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H.,
RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SEF2-1B AND SEF2-1D).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-278 (ISOFORM SEF2-1A).
RA Gu J., Zhao M., Huang Q., Xu X., Li Y., Peng Y., Song H., Xiao H.,
RA Gu Y., Li N., Qian B., Liu F., Qu J., Gao X., Cheng Z., Xu Z.,
RA Zeng L., Xu S., Gu W., Tu Y., Jia J., Fu G., Ren S., Zhong M., Lu G.,
RA Yang Y., Gao G., Zhang Q., Chen S., Han Z., Chen Z.;
RT "MDSDCE06_MDS Homo sapiens cDNA clone MDSDCE06 5',mRNA sequence.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-48.
RC TISSUE=Skin fibroblast;
RX PubMed=9302263; DOI=10.1093/hmg/6.11.1855;
RA Breschel T.S., McInnis M.G., Margolis R.L., Sirugo G.,
RA Corneliussen B., Simpson S.G., McMahon F.J., Mackinnon D.F., Xu J.F.,
RA Pleasant N., Huo Y., Ashworth R.G., Grundstrom C., Grundstrom T.,
RA Kidd K.K., Depaulo J.R., Ross C.A.;
RT "A novel, heritable, expanding CTG repeat in an intron of the SEF2-1
RT gene on chromosome 18q21.1.";
RL Hum. Mol. Genet. 6:1855-1863(1997).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 46-667 (ISOFORM SEF2-1B).
RX PubMed=2308860; DOI=10.1093/nar/18.3.678;
RA Henthorn P., McCarrick-Walmsley R., Kadesch T.;
RT "Sequence of the cDNA encoding ITF-2, a positive-acting transcription
RT factor.";
RL Nucleic Acids Res. 18:678-678(1990).
RN [10]
RP DISCUSSION OF SEQUENCE.
RX PubMed=2105528; DOI=10.1126/science.2105528;
RA Henthorn P., Kiledjian M., Kadesch T.;
RT "Two distinct transcription factors that bind the immunoglobulin
RT enhancer microE5/kappa 2 motif.";
RL Science 247:467-470(1990).
RN [11]
RP DOMAIN.
RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003;
RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P.,
RA Piskacek M.;
RT "Nine-amino-acid transactivation domain: establishment and prediction
RT utilities.";
RL Genomics 89:756-768(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-515, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [13]
RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS PTHS VAL-358;
RP GLY-535; PRO-574; TRP-576 AND VAL-610.
RX PubMed=22777675; DOI=10.1002/humu.22160;
RA Forrest M., Chapman R.M., Doyle A.M., Tinsley C.L., Waite A.,
RA Blake D.J.;
RT "Functional analysis of TCF4 missense mutations that cause Pitt-
RT Hopkins syndrome.";
RL Hum. Mutat. 33:1676-1686(2012).
RN [14]
RP INTERACTION WITH AGBL1.
RX PubMed=24094747; DOI=10.1016/j.ajhg.2013.08.010;
RA Riazuddin S.A., Vasanth S., Katsanis N., Gottsch J.D.;
RT "Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy
RT and alter protein-protein interaction with TCF4.";
RL Am. J. Hum. Genet. 93:758-764(2013).
RN [15]
RP INTERACTION WITH BHLHA9.
RX PubMed=25466284; DOI=10.1016/j.ajhg.2014.10.012;
RA Malik S., Percin F.E., Bornholdt D., Albrecht B., Percesepe A.,
RA Koch M.C., Landi A., Fritz B., Khan R., Mumtaz S., Akarsu N.A.,
RA Grzeschik K.H.;
RT "Mutations affecting the BHLHA9 DNA-binding domain cause MSSD,
RT mesoaxial synostotic syndactyly with phalangeal reduction, Malik-
RT Percin type.";
RL Am. J. Hum. Genet. 95:649-659(2014).
RN [16]
RP VARIANTS PTHS TRP-576 AND GLN-576.
RX PubMed=17436254; DOI=10.1086/515582;
RA Amiel J., Rio M., de Pontual L., Redon R., Malan V., Boddaert N.,
RA Plouin P., Carter N.P., Lyonnet S., Munnich A., Colleaux L.;
RT "Mutations in TCF4, encoding a class I basic helix-loop-helix
RT transcription factor, are responsible for Pitt-Hopkins syndrome, a
RT severe epileptic encephalopathy associated with autonomic
RT dysfunction.";
RL Am. J. Hum. Genet. 80:988-993(2007).
RN [17]
RP VARIANT PTHS TRP-576.
RX PubMed=17436255; DOI=10.1086/515583;
RA Zweier C., Peippo M.M., Hoyer J., Sousa S., Bottani A.,
RA Clayton-Smith J., Reardon W., Saraiva J., Cabral A., Goehring I.,
RA Devriendt K., de Ravel T., Bijlsma E.K., Hennekam R.C.M., Orrico A.,
RA Cohen M., Dreweke A., Reis A., Nuernberg P., Rauch A.;
RT "Haploinsufficiency of TCF4 causes syndromal mental retardation with
RT intermittent hyperventilation (Pitt-Hopkins syndrome).";
RL Am. J. Hum. Genet. 80:994-1001(2007).
RN [18]
RP VARIANTS PTHS VAL-358; PRO-574 AND HIS-578.
RX PubMed=18728071; DOI=10.1136/jmg.2008.060129;
RA Zweier C., Sticht H., Bijlsma E.K., Clayton-Smith J., Boonen S.E.,
RA Fryer A., Greally M.T., Hoffmann L., den Hollander N.S., Jongmans M.,
RA Kant S.G., King M.D., Lynch S.A., McKee S., Midro A.T., Park S.M.,
RA Ricotti V., Tarantino E., Wessels M., Peippo M., Rauch A.;
RT "Further delineation of Pitt-Hopkins syndrome: phenotypic and
RT genotypic description of 16 novel patients.";
RL J. Med. Genet. 45:738-744(2008).
RN [19]
RP VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND VAL-610, AND
RP CHARACTERIZATION OF VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND
RP VAL-610.
RX PubMed=19235238; DOI=10.1002/humu.20935;
RA de Pontual L., Mathieu Y., Golzio C., Rio M., Malan V., Boddaert N.,
RA Soufflet C., Picard C., Durandy A., Dobbie A., Heron D., Isidor B.,
RA Motte J., Newburry-Ecob R., Pasquier L., Tardieu M., Viot G.,
RA Jaubert F., Munnich A., Colleaux L., Vekemans M., Etchevers H.,
RA Lyonnet S., Amiel J.;
RT "Mutational, functional, and expression studies of the TCF4 gene in
RT Pitt-Hopkins syndrome.";
RL Hum. Mutat. 30:669-676(2009).
RN [20]
RP VARIANT PTHS PRO-578.
RX PubMed=20184619; DOI=10.1111/j.1399-0004.2010.01380.x;
RA Takano K., Lyons M., Moyes C., Jones J., Schwartz C.E.;
RT "Two percent of patients suspected of having Angelman syndrome have
RT TCF4 mutations.";
RL Clin. Genet. 78:282-288(2010).
RN [21]
RP VARIANTS PTHS TRP-565; GLY-572; GLN-572; HIS-574; PRO-574; TRP-576;
RP GLN-576; PRO-578; PRO-583 AND VAL-610.
RX PubMed=22045651; DOI=10.1002/humu.21639;
RA Whalen S., Heron D., Gaillon T., Moldovan O., Rossi M., Devillard F.,
RA Giuliano F., Soares G., Mathieu-Dramard M., Afenjar A., Charles P.,
RA Mignot C., Burglen L., Van Maldergem L., Piard J., Aftimos S.,
RA Mancini G., Dias P., Philip N., Goldenberg A., Le Merrer M., Rio M.,
RA Josifova D., Van Hagen J.M., Lacombe D., Edery P., Dupuis-Girod S.,
RA Putoux A., Sanlaville D., Fischer R., Drevillon L., Briand-Suleau A.,
RA Metay C., Goossens M., Amiel J., Jacquette A., Giurgea I.;
RT "Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome:
RT clinical score and further delineation of the TCF4 mutational
RT spectrum.";
RL Hum. Mutat. 33:64-72(2012).
CC -!- FUNCTION: Transcription factor that binds to the immunoglobulin
CC enchancer Mu-E5/KE5-motif. Involved in the initiation of neuronal
CC differentiation. Activates transcription by binding to the E box
CC (5'-CANNTG-3'). Binds to the E-box present in the somatostatin
CC receptor 2 initiator element (SSTR2-INR) to activate transcription
CC (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or
CC 5'-CCANNTGG-3'. {ECO:0000250}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another
CC bHLH protein. Forms homo- or heterooligomers with myogenin.
CC Interacts with HIVEP2. Interacts with NEUROD2 (By similarity).
CC Interacts with AGBL1. Interacts with BHLHA9. {ECO:0000250,
CC ECO:0000269|PubMed:24094747, ECO:0000269|PubMed:25466284}.
CC -!- INTERACTION:
CC Q53FW8:-; NbExp=3; IntAct=EBI-533224, EBI-10242473;
CC Q08117:AES; NbExp=3; IntAct=EBI-533224, EBI-717810;
CC P29972:AQP1; NbExp=3; IntAct=EBI-533224, EBI-745213;
CC Q92888:ARHGEF1; NbExp=3; IntAct=EBI-533224, EBI-465400;
CC Q9H6L4:ARMC7; NbExp=3; IntAct=EBI-533224, EBI-742909;
CC P50553:ASCL1; NbExp=7; IntAct=EBI-533224, EBI-957042;
CC Q6XD76:ASCL4; NbExp=3; IntAct=EBI-533224, EBI-10254793;
CC Q9BZE9:ASPSCR1; NbExp=3; IntAct=EBI-533224, EBI-1993677;
CC P21281:ATP6V1B2; NbExp=3; IntAct=EBI-533224, EBI-4290814;
CC O75934:BCAS2; NbExp=3; IntAct=EBI-533224, EBI-1050106;
CC Q92843:BCL2L2; NbExp=3; IntAct=EBI-533224, EBI-707714;
CC Q9NUL5:C19orf66; NbExp=3; IntAct=EBI-533224, EBI-10313866;
CC Q9NX04:C1orf109; NbExp=3; IntAct=EBI-533224, EBI-8643161;
CC Q6ZQR2:C9orf171; NbExp=3; IntAct=EBI-533224, EBI-10255140;
CC Q9NP86:CABP5; NbExp=3; IntAct=EBI-533224, EBI-10311131;
CC Q96ES7:CCDC101; NbExp=3; IntAct=EBI-533224, EBI-743117;
CC P38936:CDKN1A; NbExp=3; IntAct=EBI-533224, EBI-375077;
CC P42773:CDKN2C; NbExp=3; IntAct=EBI-533224, EBI-711290;
CC Q13111:CHAF1A; NbExp=3; IntAct=EBI-533224, EBI-1020839;
CC Q9Y6H1:CHCHD2; NbExp=3; IntAct=EBI-533224, EBI-2321769;
CC Q9UKJ5:CHIC2; NbExp=3; IntAct=EBI-533224, EBI-741528;
CC P61024:CKS1B; NbExp=3; IntAct=EBI-533224, EBI-456371;
CC P35222:CTNNB1; NbExp=19; IntAct=EBI-533224, EBI-491549;
CC P26233:ctnnb1 (xeno); NbExp=2; IntAct=EBI-533224, EBI-7373758;
CC P26196:DDX6; NbExp=3; IntAct=EBI-533224, EBI-351257;
CC Q9H4E7:DEF6; NbExp=3; IntAct=EBI-533224, EBI-745369;
CC Q9NQL9:DMRT3; NbExp=3; IntAct=EBI-533224, EBI-9679045;
CC Q5JVL4:EFHC1; NbExp=6; IntAct=EBI-533224, EBI-743105;
CC O60573:EIF4E2; NbExp=3; IntAct=EBI-533224, EBI-398610;
CC Q13541:EIF4EBP1; NbExp=3; IntAct=EBI-533224, EBI-74090;
CC Q9Y2J2-3:EPB41L3; NbExp=3; IntAct=EBI-533224, EBI-10326138;
CC O15197-2:EPHB6; NbExp=3; IntAct=EBI-533224, EBI-10182490;
CC Q9Y3B2:EXOSC1; NbExp=3; IntAct=EBI-533224, EBI-371892;
CC P16930:FAH; NbExp=3; IntAct=EBI-533224, EBI-4397076;
CC Q9H5Z6:FAM124B; NbExp=3; IntAct=EBI-533224, EBI-741626;
CC Q5TZK3:FAM74A6; NbExp=3; IntAct=EBI-533224, EBI-10247271;
CC Q96RJ6:FERD3L; NbExp=3; IntAct=EBI-533224, EBI-10183007;
CC Q96AC1:FERMT2; NbExp=6; IntAct=EBI-533224, EBI-4399465;
CC Q8NFF5:FLAD1; NbExp=3; IntAct=EBI-533224, EBI-742815;
CC P21333-2:FLNA; NbExp=3; IntAct=EBI-533224, EBI-9641086;
CC O43559:FRS3; NbExp=3; IntAct=EBI-533224, EBI-725515;
CC P55040:GEM; NbExp=3; IntAct=EBI-533224, EBI-744104;
CC O76003:GLRX3; NbExp=3; IntAct=EBI-533224, EBI-374781;
CC P50151:GNG10; NbExp=3; IntAct=EBI-533224, EBI-10211741;
CC Q0D2H9:GOLGA8DP; NbExp=3; IntAct=EBI-533224, EBI-10181276;
CC Q08AF8:GOLGA8G; NbExp=3; IntAct=EBI-533224, EBI-10181260;
CC Q9H8Y8:GORASP2; NbExp=3; IntAct=EBI-533224, EBI-739467;
CC Q96NT3:GUCD1; NbExp=3; IntAct=EBI-533224, EBI-8293751;
CC P61296:HAND2; NbExp=3; IntAct=EBI-533224, EBI-10218584;
CC O14929:HAT1; NbExp=3; IntAct=EBI-533224, EBI-2339359;
CC V9HWF5:HEL-S-69p; NbExp=3; IntAct=EBI-533224, EBI-10330249;
CC Q9UBY9:HSPB7; NbExp=3; IntAct=EBI-533224, EBI-739361;
CC Q02535:ID3; NbExp=3; IntAct=EBI-533224, EBI-1387094;
CC I3WAC9:INS; NbExp=3; IntAct=EBI-533224, EBI-10178524;
CC Q9BQ13:KCTD14; NbExp=3; IntAct=EBI-533224, EBI-10189448;
CC Q6P597:KLC3; NbExp=3; IntAct=EBI-533224, EBI-1643885;
CC Q5THT1:KLHL32; NbExp=3; IntAct=EBI-533224, EBI-10247181;
CC Q14847:LASP1; NbExp=3; IntAct=EBI-533224, EBI-742828;
CC Q96BZ8:LENG1; NbExp=3; IntAct=EBI-533224, EBI-726510;
CC Q8TCE9:LGALS14; NbExp=3; IntAct=EBI-533224, EBI-10274069;
CC P25800:LMO1; NbExp=3; IntAct=EBI-533224, EBI-8639312;
CC P61968:LMO4; NbExp=3; IntAct=EBI-533224, EBI-2798728;
CC Q9UIQ6:LNPEP; NbExp=3; IntAct=EBI-533224, EBI-2805360;
CC Q9UI95:MAD2L2; NbExp=3; IntAct=EBI-533224, EBI-77889;
CC Q96A72:MAGOHB; NbExp=3; IntAct=EBI-533224, EBI-746778;
CC O60336:MAPKBP1; NbExp=3; IntAct=EBI-533224, EBI-947402;
CC O15232:MATN3; NbExp=3; IntAct=EBI-533224, EBI-6262458;
CC Q9Y316:MEMO1; NbExp=3; IntAct=EBI-533224, EBI-1104564;
CC Q6P2C6:MLLT6; NbExp=3; IntAct=EBI-533224, EBI-5773143;
CC Q8NDC4:MORN4; NbExp=3; IntAct=EBI-533224, EBI-10269566;
CC Q96HT8:MRFAP1L1; NbExp=3; IntAct=EBI-533224, EBI-748896;
CC Q7Z7H8:MRPL10; NbExp=3; IntAct=EBI-533224, EBI-723524;
CC Q8IXL7:MSRB3; NbExp=3; IntAct=EBI-533224, EBI-8634060;
CC Q9ULV0:MYO5B; NbExp=3; IntAct=EBI-533224, EBI-311356;
CC O43639:NCK2; NbExp=3; IntAct=EBI-533224, EBI-713635;
CC Q9UHB4:NDOR1; NbExp=3; IntAct=EBI-533224, EBI-10249760;
CC Q9HC98:NEK6; NbExp=3; IntAct=EBI-533224, EBI-740364;
CC Q86SG6:NEK8; NbExp=3; IntAct=EBI-533224, EBI-1752987;
CC Q8WWR8-2:NEU4; NbExp=3; IntAct=EBI-533224, EBI-10277551;
CC Q92886:NEUROG1; NbExp=3; IntAct=EBI-533224, EBI-10279647;
CC Q9Y5B8:NME7; NbExp=3; IntAct=EBI-533224, EBI-744782;
CC Q9GZQ4:NMUR2; NbExp=3; IntAct=EBI-533224, EBI-10303844;
CC Q5SY16:NOL9; NbExp=3; IntAct=EBI-533224, EBI-1055462;
CC Q86WQ0:NR2C2AP; NbExp=3; IntAct=EBI-533224, EBI-10260040;
CC Q8NFP7:NUDT10; NbExp=3; IntAct=EBI-533224, EBI-726826;
CC O43929:ORC4; NbExp=3; IntAct=EBI-533224, EBI-374889;
CC Q9UJX0:OSGIN1; NbExp=3; IntAct=EBI-533224, EBI-9057006;
CC Q01804:OTUD4; NbExp=3; IntAct=EBI-533224, EBI-1054396;
CC Q8WXA2:PATE1; NbExp=3; IntAct=EBI-533224, EBI-10277790;
CC P30039:PBLD; NbExp=3; IntAct=EBI-533224, EBI-750589;
CC Q13526:PIN1; NbExp=3; IntAct=EBI-533224, EBI-714158;
CC Q494U1:PLEKHN1; NbExp=3; IntAct=EBI-533224, EBI-10241513;
CC O95602:POLR1A; NbExp=3; IntAct=EBI-533224, EBI-359472;
CC O15160:POLR1C; NbExp=3; IntAct=EBI-533224, EBI-1055079;
CC Q9Y3C6:PPIL1; NbExp=3; IntAct=EBI-533224, EBI-2557649;
CC Q6NYC8:PPP1R18; NbExp=3; IntAct=EBI-533224, EBI-2557469;
CC P54646:PRKAA2; NbExp=3; IntAct=EBI-533224, EBI-1383852;
CC P25786:PSMA1; NbExp=3; IntAct=EBI-533224, EBI-359352;
CC Q969U7:PSMG2; NbExp=3; IntAct=EBI-533224, EBI-723276;
CC Q147X8:PTGER3; NbExp=3; IntAct=EBI-533224, EBI-10234038;
CC Q5JT25:RAB41; NbExp=3; IntAct=EBI-533224, EBI-10244509;
CC P47224:RABIF; NbExp=3; IntAct=EBI-533224, EBI-713992;
CC Q6P9E2:RECK; NbExp=3; IntAct=EBI-533224, EBI-10253121;
CC Q04206-3:RELA; NbExp=3; IntAct=EBI-533224, EBI-10223388;
CC Q8IX06:REXO1L1P; NbExp=3; IntAct=EBI-533224, EBI-10262361;
CC Q9UHP6:RSPH14; NbExp=3; IntAct=EBI-533224, EBI-748350;
CC Q9UIL1:SCOC; NbExp=3; IntAct=EBI-533224, EBI-2686537;
CC Q9UDX3:SEC14L4; NbExp=3; IntAct=EBI-533224, EBI-10320311;
CC Q6NXQ0:SFRS2; NbExp=3; IntAct=EBI-533224, EBI-10251550;
CC O43699:SIGLEC6; NbExp=3; IntAct=EBI-533224, EBI-2814604;
CC Q96H72:SLC39A13; NbExp=3; IntAct=EBI-533224, EBI-10287091;
CC Q9BWU0:SLC4A1AP; NbExp=3; IntAct=EBI-533224, EBI-1999704;
CC P49901:SMCP; NbExp=3; IntAct=EBI-533224, EBI-750494;
CC Q9H4F8:SMOC1; NbExp=3; IntAct=EBI-533224, EBI-2801103;
CC Q61473:Sox17 (xeno); NbExp=5; IntAct=EBI-533224, EBI-9106822;
CC Q06831:Sox4 (xeno); NbExp=2; IntAct=EBI-533224, EBI-6262177;
CC Q9H0A9:SPATC1L; NbExp=3; IntAct=EBI-533224, EBI-372911;
CC Q9NZD8:SPG21; NbExp=3; IntAct=EBI-533224, EBI-742688;
CC Q96FJ0:STAMBPL1; NbExp=3; IntAct=EBI-533224, EBI-745021;
CC O75716:STK16; NbExp=3; IntAct=EBI-533224, EBI-749295;
CC O75558:STX11; NbExp=3; IntAct=EBI-533224, EBI-714135;
CC Q5T011-5:SZT2; NbExp=3; IntAct=EBI-533224, EBI-10245139;
CC Q16559:TAL2; NbExp=3; IntAct=EBI-533224, EBI-10237959;
CC Q15560:TCEA2; NbExp=3; IntAct=EBI-533224, EBI-710310;
CC P56279:TCL1A; NbExp=3; IntAct=EBI-533224, EBI-749995;
CC Q9UL33:TRAPPC2L; NbExp=3; IntAct=EBI-533224, EBI-747601;
CC Q96PN8:TSSK3; NbExp=3; IntAct=EBI-533224, EBI-3918381;
CC Q8WVJ9:TWIST2; NbExp=3; IntAct=EBI-533224, EBI-1797313;
CC Q9NX01:TXNL4B; NbExp=3; IntAct=EBI-533224, EBI-10309345;
CC Q9BRU9:UTP23; NbExp=3; IntAct=EBI-533224, EBI-5457544;
CC Q548N1:VPS28; NbExp=3; IntAct=EBI-533224, EBI-10243107;
CC Q6UX98:ZDHHC24; NbExp=3; IntAct=EBI-533224, EBI-10254561;
CC Q15973:ZNF124; NbExp=3; IntAct=EBI-533224, EBI-2555767;
CC Q8TAU3:ZNF417; NbExp=3; IntAct=EBI-533224, EBI-740727;
CC Q96SQ5:ZNF587; NbExp=3; IntAct=EBI-533224, EBI-6427977;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
CC ProRule:PRU00981, ECO:0000269|PubMed:22777675}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=16;
CC Comment=Additional isoforms seem to exist.;
CC Name=SEF2-1B; Synonyms=B-;
CC IsoId=P15884-1; Sequence=Displayed;
CC Name=SEF2-1A; Synonyms=A+;
CC IsoId=P15884-2; Sequence=VSP_030819, VSP_002111, VSP_002112;
CC Name=SEF2-1D; Synonyms=B+;
CC IsoId=P15884-3; Sequence=VSP_002112;
CC Name=B+delta;
CC IsoId=P15884-4; Sequence=VSP_044340, VSP_002112;
CC Name=B-delta;
CC IsoId=P15884-5; Sequence=VSP_044340;
CC Name=A-;
CC IsoId=P15884-6; Sequence=VSP_044336, VSP_044337, VSP_044340;
CC Name=G-;
CC IsoId=P15884-7; Sequence=VSP_044334, VSP_044338, VSP_044339;
CC Name=H-;
CC IsoId=P15884-8; Sequence=VSP_044335, VSP_057364;
CC Name=D-;
CC IsoId=P15884-9; Sequence=VSP_045149;
CC Name=F-;
CC IsoId=P15884-10; Sequence=VSP_045151;
CC Name=11;
CC IsoId=P15884-11; Sequence=VSP_045150, VSP_044339, VSP_002112;
CC Name=E-;
CC IsoId=P15884-12; Sequence=VSP_047082, VSP_047083;
CC Name=13;
CC IsoId=P15884-13; Sequence=VSP_047081, VSP_002112;
CC Name=C-;
CC IsoId=P15884-14; Sequence=VSP_047081;
CC Name=C-delta;
CC IsoId=P15884-15; Sequence=VSP_047081, VSP_044340;
CC Name=I-;
CC IsoId=P15884-16; Sequence=VSP_054279;
CC -!- TISSUE SPECIFICITY: Expressed in adult heart, brain, placenta,
CC skeletal muscle and to a lesser extent in the lung. In developing
CC embryonic tissues, expression mostly occurs in the brain.
CC -!- DOMAIN: the 9aaTAD motif is a transactivation domain present in a
CC large number of yeast and animal transcription factors.
CC {ECO:0000269|PubMed:17467953}.
CC -!- DISEASE: Pitt-Hopkins syndrome (PTHS) [MIM:610954]: A syndrome
CC characterized by mental retardation, wide mouth and distinctive
CC facial features, and intermittent hyperventilation followed by
CC apnea. Features include intellectual disability with severe speech
CC impairment, normal growth parameters at birth, postnatal
CC microcephaly, breathing anomalies, severe motor developmental
CC delay, motor incoordination, ocular anomalies, constipation,
CC seizures, typical behavior and subtle brain abnormalities.
CC {ECO:0000269|PubMed:17436254, ECO:0000269|PubMed:17436255,
CC ECO:0000269|PubMed:18728071, ECO:0000269|PubMed:19235238,
CC ECO:0000269|PubMed:20184619, ECO:0000269|PubMed:22045651}.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60310.1; Type=Miscellaneous discrepancy; Note=Incomplete and probable erroneous sequence.; Evidence={ECO:0000305};
CC Sequence=AAA60312.1; Type=Miscellaneous discrepancy; Note=Incomplete and probable erroneous sequence.; Evidence={ECO:0000305};
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DR EMBL; M74718; AAA60310.1; ALT_SEQ; mRNA.
DR EMBL; M74719; AAA60311.1; -; mRNA.
DR EMBL; M74720; AAA60312.1; ALT_SEQ; mRNA.
DR EMBL; FR748210; CBY80189.1; -; mRNA.
DR EMBL; FR748211; CBY80190.1; -; mRNA.
DR EMBL; FR748212; CBY80191.1; -; mRNA.
DR EMBL; FR748213; CBY80192.1; -; mRNA.
DR EMBL; FR748214; CBY80193.1; -; mRNA.
DR EMBL; FR748215; CBY80194.1; -; mRNA.
DR EMBL; FR748216; CBY80195.1; -; mRNA.
DR EMBL; FR748217; CBY80196.1; -; mRNA.
DR EMBL; FR748218; CBY80197.1; -; mRNA.
DR EMBL; FR748219; CBY80198.1; -; mRNA.
DR EMBL; FR748220; CBY80199.1; -; mRNA.
DR EMBL; FR748221; CBY80200.1; -; mRNA.
DR EMBL; FR748222; CBY80201.1; -; mRNA.
DR EMBL; FR748223; CBY80202.1; -; mRNA.
DR EMBL; AK095041; BAG52974.1; -; mRNA.
DR EMBL; AK096862; BAG53382.1; -; mRNA.
DR EMBL; AK299169; BAH12962.1; -; mRNA.
DR EMBL; AK300636; BAG62325.1; -; mRNA.
DR EMBL; AK300038; BAG61849.1; -; mRNA.
DR EMBL; AK301144; BAH13417.1; -; mRNA.
DR EMBL; AK300612; BAH13314.1; -; mRNA.
DR EMBL; AK316165; BAH14536.1; -; mRNA.
DR EMBL; AC013587; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC018994; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090684; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091103; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471096; EAW63017.1; -; Genomic_DNA.
DR EMBL; CH471096; EAW63018.1; -; Genomic_DNA.
DR EMBL; BC125084; AAI25085.1; -; mRNA.
DR EMBL; BC125085; AAI25086.1; -; mRNA.
DR EMBL; AV761952; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; U75701; AAC51824.1; -; Genomic_DNA.
DR EMBL; X52079; CAA36298.1; -; mRNA.
DR CCDS; CCDS11960.1; -. [P15884-1]
DR CCDS; CCDS42438.1; -. [P15884-3]
DR CCDS; CCDS58623.1; -. [P15884-8]
DR CCDS; CCDS58624.1; -. [P15884-2]
DR CCDS; CCDS58625.1; -. [P15884-6]
DR CCDS; CCDS58626.1; -. [P15884-9]
DR CCDS; CCDS58627.1; -. [P15884-11]
DR CCDS; CCDS58628.1; -. [P15884-10]
DR CCDS; CCDS58629.1; -. [P15884-13]
DR CCDS; CCDS59321.1; -. [P15884-12]
DR CCDS; CCDS77191.1; -. [P15884-7]
DR CCDS; CCDS77192.1; -. [P15884-14]
DR PIR; A41311; A41311.
DR RefSeq; NP_001077431.1; NM_001083962.1. [P15884-3]
DR RefSeq; NP_001230155.2; NM_001243226.2.
DR RefSeq; NP_001230156.1; NM_001243227.1. [P15884-13]
DR RefSeq; NP_001230157.1; NM_001243228.1.
DR RefSeq; NP_001230159.1; NM_001243230.1. [P15884-12]
DR RefSeq; NP_001230160.1; NM_001243231.1. [P15884-10]
DR RefSeq; NP_001230161.1; NM_001243232.1. [P15884-11]
DR RefSeq; NP_001230162.1; NM_001243233.1. [P15884-9]
DR RefSeq; NP_001230163.1; NM_001243234.1. [P15884-2]
DR RefSeq; NP_001230164.1; NM_001243235.1. [P15884-6]
DR RefSeq; NP_001230165.1; NM_001243236.1. [P15884-8]
DR RefSeq; NP_001293136.1; NM_001306207.1. [P15884-14]
DR RefSeq; NP_001293137.1; NM_001306208.1. [P15884-7]
DR RefSeq; NP_003190.1; NM_003199.2. [P15884-1]
DR RefSeq; XP_005266796.2; XM_005266739.3. [P15884-13]
DR RefSeq; XP_005266800.1; XM_005266743.3. [P15884-13]
DR RefSeq; XP_005266801.1; XM_005266744.3. [P15884-13]
DR RefSeq; XP_006722599.1; XM_006722536.2. [P15884-3]
DR RefSeq; XP_006722600.1; XM_006722537.2. [P15884-3]
DR RefSeq; XP_006722603.1; XM_006722540.2. [P15884-9]
DR RefSeq; XP_011524466.1; XM_011526164.1. [P15884-9]
DR UniGene; Hs.605153; -.
DR UniGene; Hs.742885; -.
DR PDB; 2KWF; NMR; -; B=11-27.
DR PDBsum; 2KWF; -.
DR DisProt; DP00224; -.
DR ProteinModelPortal; P15884; -.
DR SMR; P15884; 565-624.
DR BioGrid; 112787; 193.
DR DIP; DIP-163N; -.
DR IntAct; P15884; 151.
DR MINT; MINT-4508073; -.
DR STRING; 9606.ENSP00000346440; -.
DR PhosphoSite; P15884; -.
DR BioMuta; TCF4; -.
DR MaxQB; P15884; -.
DR PaxDb; P15884; -.
DR PRIDE; P15884; -.
DR Ensembl; ENST00000354452; ENSP00000346440; ENSG00000196628. [P15884-3]
DR Ensembl; ENST00000356073; ENSP00000348374; ENSG00000196628. [P15884-1]
DR Ensembl; ENST00000457482; ENSP00000409447; ENSG00000196628. [P15884-2]
DR Ensembl; ENST00000537578; ENSP00000440731; ENSG00000196628. [P15884-13]
DR Ensembl; ENST00000537856; ENSP00000439827; ENSG00000196628. [P15884-9]
DR Ensembl; ENST00000540999; ENSP00000445202; ENSG00000196628. [P15884-14]
DR Ensembl; ENST00000543082; ENSP00000439656; ENSG00000196628. [P15884-10]
DR Ensembl; ENST00000544241; ENSP00000441562; ENSG00000196628. [P15884-11]
DR Ensembl; ENST00000561831; ENSP00000457765; ENSG00000196628. [P15884-8]
DR Ensembl; ENST00000561992; ENSP00000455179; ENSG00000196628. [P15884-9]
DR Ensembl; ENST00000564228; ENSP00000455261; ENSG00000196628. [P15884-7]
DR Ensembl; ENST00000564999; ENSP00000457649; ENSG00000196628. [P15884-1]
DR Ensembl; ENST00000565018; ENSP00000455984; ENSG00000196628. [P15884-15]
DR Ensembl; ENST00000566279; ENSP00000456125; ENSG00000196628. [P15884-4]
DR Ensembl; ENST00000566286; ENSP00000455418; ENSG00000196628. [P15884-12]
DR Ensembl; ENST00000567880; ENSP00000454366; ENSG00000196628. [P15884-5]
DR Ensembl; ENST00000568673; ENSP00000455135; ENSG00000196628. [P15884-13]
DR Ensembl; ENST00000570177; ENSP00000454647; ENSG00000196628. [P15884-9]
DR Ensembl; ENST00000570287; ENSP00000455763; ENSG00000196628. [P15884-6]
DR Ensembl; ENST00000616053; ENSP00000478549; ENSG00000196628. [P15884-15]
DR Ensembl; ENST00000626584; ENSP00000486072; ENSG00000196628. [P15884-16]
DR Ensembl; ENST00000629387; ENSP00000486670; ENSG00000196628. [P15884-3]
DR GeneID; 6925; -.
DR KEGG; hsa:6925; -.
DR UCSC; uc002lfw.4; human. [P15884-2]
DR UCSC; uc002lfx.2; human.
DR UCSC; uc002lfy.2; human.
DR UCSC; uc002lfz.2; human. [P15884-1]
DR UCSC; uc010dph.1; human. [P15884-3]
DR UCSC; uc010xdy.1; human.
DR UCSC; uc021ukh.1; human. [P15884-6]
DR UCSC; uc021uki.1; human. [P15884-7]
DR UCSC; uc021ukj.1; human. [P15884-5]
DR UCSC; uc021ukk.1; human. [P15884-4]
DR CTD; 6925; -.
DR GeneCards; TCF4; -.
DR GeneReviews; TCF4; -.
DR HGNC; HGNC:11634; TCF4.
DR HPA; CAB020722; -.
DR HPA; HPA025958; -.
DR MIM; 602272; gene.
DR MIM; 610954; phenotype.
DR neXtProt; NX_P15884; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 98974; Fuchs endothelial corneal dystrophy.
DR Orphanet; 2896; Pitt-Hopkins syndrome.
DR Orphanet; 171; Primary sclerosing cholangitis.
DR Orphanet; 3140; Schizophrenia.
DR PharmGKB; PA164742621; -.
DR eggNOG; KOG3910; Eukaryota.
DR eggNOG; ENOG410XYUA; LUCA.
DR GeneTree; ENSGT00510000046438; -.
DR HOGENOM; HOG000234180; -.
DR HOVERGEN; HBG003854; -.
DR InParanoid; P15884; -.
DR KO; K15603; -.
DR OrthoDB; EOG72G16Q; -.
DR PhylomeDB; P15884; -.
DR TreeFam; TF321672; -.
DR Reactome; R-HSA-375170; CDO in myogenesis.
DR SignaLink; P15884; -.
DR ChiTaRS; TCF4; human.
DR EvolutionaryTrace; P15884; -.
DR GeneWiki; TCF4; -.
DR GenomeRNAi; 6925; -.
DR NextBio; 27093; -.
DR PRO; PR:P15884; -.
DR Proteomes; UP000005640; Chromosome 18.
DR Bgee; P15884; -.
DR CleanEx; HS_TCF4; -.
DR ExpressionAtlas; P15884; baseline and differential.
DR Genevisible; P15884; HS.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription factor complex; ISS:BHF-UCL.
DR GO; GO:0043425; F:bHLH transcription factor binding; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; ISS:BHF-UCL.
DR GO; GO:0001093; F:TFIIB-class transcription factor binding; ISS:BHF-UCL.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001011; F:transcription factor activity, sequence-specific DNA binding, RNA polymerase recruiting; ISS:BHF-UCL.
DR GO; GO:0001087; F:transcription factor activity, TFIIB-class binding; ISS:BHF-UCL.
DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISS:BHF-UCL.
DR GO; GO:0006352; P:DNA-templated transcription, initiation; ISS:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0065004; P:protein-DNA complex assembly; ISS:BHF-UCL.
DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; ISS:BHF-UCL.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Complete proteome;
KW Differentiation; Disease mutation; DNA-binding; Epilepsy;
KW Mental retardation; Neurogenesis; Nucleus; Phosphoprotein;
KW Polymorphism; Primary microcephaly; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1 667 Transcription factor 4.
FT /FTId=PRO_0000127256.
FT DOMAIN 564 617 bHLH. {ECO:0000255|PROSITE-
FT ProRule:PRU00981}.
FT REGION 1 83 Essential for MYOD1 inhibition.
FT {ECO:0000250}.
FT REGION 379 400 Leucine-zipper.
FT REGION 619 642 Class A specific domain.
FT MOTIF 18 26 9aaTAD.
FT COMPBIAS 228 231 Poly-Ser.
FT MOD_RES 372 372 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q62655}.
FT MOD_RES 515 515 Phosphoserine.
FT {ECO:0000244|PubMed:21406692}.
FT VAR_SEQ 1 216 Missing (in isoform I-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_054279.
FT VAR_SEQ 1 160 Missing (in isoform SEF2-1A).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:1681116,
FT ECO:0000303|PubMed:21789225,
FT ECO:0000303|Ref.7}.
FT /FTId=VSP_030819.
FT VAR_SEQ 1 130 Missing (in isoform D-).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_045149.
FT VAR_SEQ 1 102 MHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLA
FT SGHFTGSNVEDRSSSGSWGNGGHPSPSRNYGDGTPYDHMTS
FT RDLGSHDNLSPPFVNSRIQS -> MKDIFFQFIIARVRKCY
FT SLSCLHTLPVVPTLR (in isoform 11).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_045150.
FT VAR_SEQ 1 49 MHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLA
FT SGHFTGSN -> MEEDSRD (in isoform F-).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_045151.
FT VAR_SEQ 1 32 MHHQQRMAALGTDKELSDLLDFSAMFSPPVSS -> MKDIF
FT FQFIIARVRKCYSLSCLHTLPVVPTLR (in isoform
FT G-). {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_044334.
FT VAR_SEQ 1 24 Missing (in isoform 13, isoform C- and
FT isoform C-delta).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_047081.
FT VAR_SEQ 1 24 MHHQQRMAALGTDKELSDLLDFSA -> MQRAKTELFRLQI
FT VTDDLRKNE (in isoform E-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_047082.
FT VAR_SEQ 1 23 MHHQQRMAALGTDKELSDLLDFS -> MYCAYTIPGMGGNS
FT LMYYYNGKA (in isoform A-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_044336.
FT VAR_SEQ 1 23 MHHQQRMAALGTDKELSDLLDFS -> MKFKQCRCSDTGLC
FT CLDHEGKAE (in isoform H-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_044335.
FT VAR_SEQ 24 183 Missing (in isoform H-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_057364.
FT VAR_SEQ 24 123 Missing (in isoform A-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_044337.
FT VAR_SEQ 33 102 Missing (in isoform G-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_044338.
FT VAR_SEQ 123 123 Missing (in isoform G- and isoform 11).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_044339.
FT VAR_SEQ 124 183 Missing (in isoform A-, isoform B-delta,
FT isoform B+delta and isoform C-delta).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_044340.
FT VAR_SEQ 161 183 LHSSAMEVQTKKVRKVPPGLPSS -> MYCAYTIPGMGGNS
FT LMYYYNGKA (in isoform SEF2-1A).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:1681116,
FT ECO:0000303|PubMed:21789225,
FT ECO:0000303|Ref.7}.
FT /FTId=VSP_002111.
FT VAR_SEQ 357 357 Missing (in isoform E-).
FT {ECO:0000303|PubMed:21789225}.
FT /FTId=VSP_047083.
FT VAR_SEQ 545 545 T -> TRSRS (in isoform B+delta, isoform
FT SEF2-1A, isoform SEF2-1D, isoform 11 and
FT isoform 13).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1681116,
FT ECO:0000303|PubMed:21789225,
FT ECO:0000303|Ref.7}.
FT /FTId=VSP_002112.
FT VARIANT 358 358 G -> V (in PTHS; also expressed in the
FT nucleus with a pattern indistinguishable
FT from the wild-type; does not have a major
FT impact on homodimer formation; affects
FT transcriptional activity in a context-
FT dependent manner).
FT {ECO:0000269|PubMed:18728071,
FT ECO:0000269|PubMed:22777675}.
FT /FTId=VAR_066839.
FT VARIANT 450 450 M -> I (in dbSNP:rs11660217).
FT /FTId=VAR_049545.
FT VARIANT 535 535 D -> G (in PTHS; loss of function; also
FT expressed in the nucleus with a pattern
FT indistinguishable from the wild-type;
FT does not have a major impact on homodimer
FT formation; affects transcriptional
FT activity in a context-dependent manner).
FT {ECO:0000269|PubMed:19235238,
FT ECO:0000269|PubMed:22777675}.
FT /FTId=VAR_058632.
FT VARIANT 565 565 R -> W (in PTHS).
FT {ECO:0000269|PubMed:22045651}.
FT /FTId=VAR_066970.
FT VARIANT 572 572 R -> G (in PTHS; loss of function).
FT {ECO:0000269|PubMed:19235238,
FT ECO:0000269|PubMed:22045651}.
FT /FTId=VAR_058633.
FT VARIANT 572 572 R -> Q (in PTHS).
FT {ECO:0000269|PubMed:22045651}.
FT /FTId=VAR_066971.
FT VARIANT 574 574 R -> H (in PTHS).
FT {ECO:0000269|PubMed:22045651}.
FT /FTId=VAR_066972.
FT VARIANT 574 574 R -> P (in PTHS; mislocalized to small
FT spherical punctae that are dispersed
FT throughout the nucleus; can attenuate
FT homo- and heterodimer formation; affects
FT transcriptional activity in a context-
FT dependent manner).
FT {ECO:0000269|PubMed:18728071,
FT ECO:0000269|PubMed:22045651,
FT ECO:0000269|PubMed:22777675}.
FT /FTId=VAR_066840.
FT VARIANT 576 576 R -> Q (in PTHS; loss of function).
FT {ECO:0000269|PubMed:17436254,
FT ECO:0000269|PubMed:19235238,
FT ECO:0000269|PubMed:22045651}.
FT /FTId=VAR_034704.
FT VARIANT 576 576 R -> W (in PTHS; mislocalized to small
FT spherical punctae that are dispersed
FT throughout the nucleus; can attenuate
FT homo- and heterodimer formation; affects
FT transcriptional activity in a context-
FT dependent manner).
FT {ECO:0000269|PubMed:17436254,
FT ECO:0000269|PubMed:17436255,
FT ECO:0000269|PubMed:22045651,
FT ECO:0000269|PubMed:22777675}.
FT /FTId=VAR_034705.
FT VARIANT 578 578 R -> H (in PTHS).
FT {ECO:0000269|PubMed:18728071}.
FT /FTId=VAR_066841.
FT VARIANT 578 578 R -> P (in PTHS).
FT {ECO:0000269|PubMed:20184619,
FT ECO:0000269|PubMed:22045651}.
FT /FTId=VAR_066973.
FT VARIANT 583 583 A -> P (in PTHS).
FT {ECO:0000269|PubMed:22045651}.
FT /FTId=VAR_066974.
FT VARIANT 610 610 A -> V (in PTHS; loss of function;
FT mislocalized to small spherical punctae
FT that are dispersed throughout the
FT nucleus; can attenuate homo- and
FT heterodimer formation; affects
FT transcriptional activity in a context-
FT dependent manner).
FT {ECO:0000269|PubMed:19235238,
FT ECO:0000269|PubMed:22045651,
FT ECO:0000269|PubMed:22777675}.
FT /FTId=VAR_058634.
FT CONFLICT 46 49 TGSN -> EFGG (in Ref. 9; CAA36298).
FT {ECO:0000305}.
FT CONFLICT 205 205 Missing (in Ref. 7; AV761952).
FT {ECO:0000305}.
FT CONFLICT 334 334 P -> S (in Ref. 9; CAA36298).
FT {ECO:0000305}.
FT HELIX 15 25 {ECO:0000244|PDB:2KWF}.
SQ SEQUENCE 667 AA; 71308 MW; 53459FC7989D9487 CRC64;
MHHQQRMAAL GTDKELSDLL DFSAMFSPPV SSGKNGPTSL ASGHFTGSNV EDRSSSGSWG
NGGHPSPSRN YGDGTPYDHM TSRDLGSHDN LSPPFVNSRI QSKTERGSYS SYGRESNLQG
CHQQSLLGGD MDMGNPGTLS PTKPGSQYYQ YSSNNPRRRP LHSSAMEVQT KKVRKVPPGL
PSSVYAPSAS TADYNRDSPG YPSSKPATST FPSSFFMQDG HHSSDPWSSS SGMNQPGYAG
MLGNSSHIPQ SSSYCSLHPH ERLSYPSHSS ADINSSLPPM STFHRSGTNH YSTSSCTPPA
NGTDSIMANR GSGAAGSSQT GDALGKALAS IYSPDHTNNS FSSNPSTPVG SPPSLSAGTA
VWSRNGGQAS SSPNYEGPLH SLQSRIEDRL ERLDDAIHVL RNHAVGPSTA MPGGHGDMHG
IIGPSHNGAM GGLGSGYGTG LLSANRHSLM VGTHREDGVA LRGSHSLLPN QVPVPQLPVQ
SATSPDLNPP QDPYRGMPPG LQGQSVSSGS SEIKSDDEGD ENLQDTKSSE DKKLDDDKKD
IKSITSNNDD EDLTPEQKAE REKERRMANN ARERLRVRDI NEAFKELGRM VQLHLKSDKP
QTKLLILHQA VAVILSLEQQ VRERNLNPKA ACLKRREEEK VSSEPPPLSL AGPHPGMGDA
SNHMGQM
//
ID KAT2B_HUMAN Reviewed; 832 AA.
AC Q92831; Q6NSK1;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 3.
DT 11-NOV-2015, entry version 171.
DE RecName: Full=Histone acetyltransferase KAT2B;
DE EC=2.3.1.48;
DE AltName: Full=Histone acetyltransferase PCAF;
DE Short=Histone acetylase PCAF;
DE AltName: Full=Lysine acetyltransferase 2B;
DE AltName: Full=P300/CBP-associated factor;
DE Short=P/CAF;
GN Name=KAT2B; Synonyms=PCAF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAC50890.2};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, TISSUE SPECIFICITY, AND
RP INTERACTION WITH EP300 AND CREBBP.
RC TISSUE=Liver;
RX PubMed=8684459; DOI=10.1038/382319a0;
RA Yang X.-J., Ogryzko V.V., Nishikawa J., Howard B.H., Nakatani Y.;
RT "A p300/CBP-associated factor that competes with the adenoviral
RT oncoprotein E1A.";
RL Nature 382:319-324(1996).
RN [2] {ECO:0000305}
RP SEQUENCE REVISION.
RC TISSUE=Liver;
RA Nakatani Y.;
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP ENZYME ACTIVITY.
RX PubMed=8945521; DOI=10.1016/S0092-8674(00)82001-2;
RA Ogryzko V.V., Schiltz R.L., Russanova V., Howard B.H., Nakatani Y.;
RT "The transcriptional coactivators p300 and CBP are histone
RT acetyltransferases.";
RL Cell 87:953-959(1996).
RN [5]
RP INTERACTION WITH NCOA3.
RX PubMed=9346901; DOI=10.1074/jbc.272.44.27629;
RA Takeshita A., Cardona G.R., Koibuchi N., Suen C.-S., Chin W.W.;
RT "TRAM-1, a novel 160-kDa thyroid hormone receptor activator molecule,
RT exhibits distinct properties from steroid receptor coactivator-1.";
RL J. Biol. Chem. 272:27629-27634(1997).
RN [6]
RP INTERACTION WITH NCOA1.
RX PubMed=9296499; DOI=10.1038/38304;
RA Spencer T.E., Jenster G., Burcin M.M., Allis C.D., Zhou J.,
RA Mizzen C.A., McKenna N.J., Onate S.A., Tsai S.Y., Tsai M.-J.,
RA O'Malley B.W.;
RT "Steroid receptor coactivator-1 is a histone acetyltransferase.";
RL Nature 389:194-198(1997).
RN [7]
RP INTERACTION WITH KLF1, AND FUNCTION.
RX PubMed=9707565; DOI=10.1073/pnas.95.17.9855;
RA Zhang W., Bieker J.J.;
RT "Acetylation and modulation of erythroid Krueppel-like factor (EKLF)
RT activity by interaction with histone acetyltransferases.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9855-9860(1998).
RN [8]
RP INTERACTION WITH E2F1, AND FUNCTION.
RX PubMed=10675335; DOI=10.1093/emboj/19.4.662;
RA Martinez-Balbas M.A., Bauer U.M., Nielsen S.J., Brehm A.,
RA Kouzarides T.;
RT "Regulation of E2F1 activity by acetylation.";
RL EMBO J. 19:662-671(2000).
RN [9]
RP INTERACTION WITH HTLV-1 TAX.
RX PubMed=10766811; DOI=10.1074/jbc.275.16.11852;
RA Harrod R., Kuo Y.-L., Tang Y., Yao Y., Vassilev A., Nakatani Y.,
RA Giam C.-Z.;
RT "p300 and p300/cAMP-responsive element-binding protein associated
RT factor interact with human T-cell lymphotropic virus type-1 Tax in a
RT multi-histone acetyltransferase/activator-enhancer complex.";
RL J. Biol. Chem. 275:11852-11857(2000).
RN [10]
RP INTERACTION WITH MECOM.
RX PubMed=11568182; DOI=10.1074/jbc.M106733200;
RA Chakraborty S., Senyuk V., Sitailo S., Chi Y., Nucifora G.;
RT "Interaction of EVI1 with cAMP-responsive element-binding protein-
RT binding protein (CBP) and p300/CBP-associated factor (P/CAF) results
RT in reversible acetylation of EVI1 and in co-localization in nuclear
RT speckles.";
RL J. Biol. Chem. 276:44936-44943(2001).
RN [11]
RP INTERACTION WITH HIV-1 TAT.
RX PubMed=12486002; DOI=10.1093/emboj/cdf669;
RA Bres V., Tagami H., Peloponese J.-M., Loret E., Jeang K.-T.,
RA Nakatani Y., Emiliani S., Benkirane M., Kiernan R.E.;
RT "Differential acetylation of Tat coordinates its interaction with the
RT co-activators cyclin T1 and PCAF.";
RL EMBO J. 21:6811-6819(2002).
RN [12]
RP FUNCTION, AND INTERACTION WITH NPAS2; ARNTL/BMAL1 AND CLOCK.
RX PubMed=14645221; DOI=10.1074/jbc.M311973200;
RA Curtis A.M., Seo S.B., Westgate E.J., Rudic R.D., Smyth E.M.,
RA Chakravarti D., FitzGerald G.A., McNamara P.;
RT "Histone acetyltransferase-dependent chromatin remodeling and the
RT vascular clock.";
RL J. Biol. Chem. 279:7091-7097(2004).
RN [13]
RP INTERACTION WITH NFE4.
RX PubMed=15273251; DOI=10.1074/jbc.M405129200;
RA Zhao Q., Cumming H., Cerruti L., Cunningham J.M., Jane S.M.;
RT "Site-specific acetylation of the fetal globin activator NF-E4
RT prevents its ubiquitination and regulates its interaction with the
RT histone deacetylase, HDAC1.";
RL J. Biol. Chem. 279:41477-41486(2004).
RN [14]
RP INTERACTION WITH TACC1; TACC2 AND TACC3.
RX PubMed=14767476; DOI=10.1038/sj.onc.1207424;
RA Gangisetty O., Lauffart B., Sondarva G.V., Chelsea D.M., Still I.H.;
RT "The transforming acidic coiled coil proteins interact with nuclear
RT histone acetyltransferases.";
RL Oncogene 23:2559-2563(2004).
RN [15]
RP INTERACTION WITH NR2C2.
RX PubMed=16887930; DOI=10.1074/mcp.M600180-MCP200;
RA Huq M.D., Gupta P., Tsai N.P., Wei L.N.;
RT "Modulation of testicular receptor 4 activity by mitogen-activated
RT protein kinase-mediated phosphorylation.";
RL Mol. Cell. Proteomics 5:2072-2082(2006).
RN [16]
RP INTERACTION WITH DDX17.
RX PubMed=17226766; DOI=10.1002/jcb.21250;
RA Shin S., Janknecht R.;
RT "Concerted activation of the Mdm2 promoter by p72 RNA helicase and the
RT coactivators p300 and P/CAF.";
RL J. Cell. Biochem. 101:1252-1265(2007).
RN [17]
RP INTERACTION WITH CEBPB.
RX PubMed=17301242; DOI=10.1073/pnas.0607378104;
RA Wiper-Bergeron N., Salem H.A., Tomlinson J.J., Wu D., Hache R.J.;
RT "Glucocorticoid-stimulated preadipocyte differentiation is mediated
RT through acetylation of C/EBPbeta by GCN5.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2703-2708(2007).
RN [18]
RP IDENTIFICATION IN A LARGE CHROMATIN REMODELING COMPLEX.
RX PubMed=17707232; DOI=10.1016/j.molcel.2007.07.024;
RA Zhu P., Zhou W., Wang J., Puc J., Ohgi K.A., Erdjument-Bromage H.,
RA Tempst P., Glass C.K., Rosenfeld M.G.;
RT "A histone H2A deubiquitinase complex coordinating histone acetylation
RT and H1 dissociation in transcriptional regulation.";
RL Mol. Cell 27:609-621(2007).
RN [19]
RP INTERACTION WITH BCAS3.
RX PubMed=17505058; DOI=10.1210/me.2006-0514;
RA Gururaj A.E., Peng S., Vadlamudi R.K., Kumar R.;
RT "Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha
RT coactivator, through proline-, glutamic acid-, and leucine-rich
RT protein-1 (PELP1).";
RL Mol. Endocrinol. 21:1847-1860(2007).
RN [20]
RP FUNCTION.
RX PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002;
RA Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.;
RT "Acetylation stabilizes ATP-citrate lyase to promote lipid
RT biosynthesis and tumor growth.";
RL Mol. Cell 51:506-518(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 493-658 IN COMPLEX WITH
RP COENZYME A, AND ACTIVE SITE.
RX PubMed=10393169; DOI=10.1093/emboj/18.13.3521;
RA Clements A., Rojas J.R., Trievel R.C., Wang L., Berger S.L.,
RA Marmorstein R.;
RT "Crystal structure of the histone acetyltransferase domain of the
RT human PCAF transcriptional regulator bound to coenzyme A.";
RL EMBO J. 18:3521-3532(1999).
RN [22]
RP STRUCTURE BY NMR OF 715-832, AND MUTAGENESIS OF VAL-752; TYR-760;
RP TYR-802 AND TYR-809.
RC TISSUE=Liver;
RX PubMed=10365964; DOI=10.1038/20974;
RA Dhalluin C., Carlson J.E., Zeng L., He C., Aggarwal A.K., Zhou M.-M.;
RT "Structure and ligand of a histone acetyltransferase bromodomain.";
RL Nature 399:491-496(1999).
RN [23]
RP STRUCTURE BY NMR OF 719-832 IN COMPLEX WITH HIV-1 TAT.
RX PubMed=11931765; DOI=10.1016/S1097-2765(02)00483-5;
RA Mujtaba S., He Y., Zeng L., Farooq A., Carlson J.E., Ott M.,
RA Verdin E., Zhou M.-M.;
RT "Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF
RT bromodomain.";
RL Mol. Cell 9:575-586(2002).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 715-831.
RX PubMed=22464331; DOI=10.1016/j.cell.2012.02.013;
RA Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P.,
RA Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T.,
RA Gingras A.C., Arrowsmith C.H., Knapp S.;
RT "Histone recognition and large-scale structural analysis of the human
RT bromodomain family.";
RL Cell 149:214-231(2012).
CC -!- FUNCTION: Functions as a histone acetyltransferase (HAT) to
CC promote transcriptional activation. Has significant histone
CC acetyltransferase activity with core histones (H3 and H4), and
CC also with nucleosome core particles. Also acetylates non-histone
CC proteins, such as ACLY. Inhibits cell-cycle progression and
CC counteracts the mitogenic activity of the adenoviral oncoprotein
CC E1A. In case of HIV-1 infection, it is recruited by the viral
CC protein Tat. Regulates Tat's transactivating activity and may help
CC inducing chromatin remodeling of proviral genes. Acts as a
CC circadian transcriptional coactivator which enhances the activity
CC of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and
CC CLOCK-ARNTL/BMAL1 heterodimers. {ECO:0000269|PubMed:10675335,
CC ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:23932781,
CC ECO:0000269|PubMed:8684459, ECO:0000269|PubMed:9707565}.
CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl-
CC [histone]. {ECO:0000269|PubMed:8945521}.
CC -!- SUBUNIT: Interacts with SIRT1. Interacts (unsumoylated form) with
CC NR2C1; the interaction promotes transactivation activity (By
CC similarity). Interacts with EP300, CREBBP and DDX17. Interacts
CC with NCOA1 and NCOA3. Component of a large chromatin remodeling
CC complex, at least composed of MYSM1, KAT2B/PCAF, RBM10 and
CC KIF11/TRIP5. Interacts with NR2C2 (hypophosphorylated and
CC unsumoylated form); the interaction promotes the transactivation
CC activity of NR2C2. Binds to HTLV-1 Tax. Interacts with and
CC acetylates HIV-1 Tat. Interacts with KLF1; the interaction does
CC not acetylate KLF1 and there is no enhancement of its
CC transactivational activity. Interacts with NFE4. Interacts with
CC MECOM. Interacts with E2F1; the interaction acetylates E2F1
CC augmenting its DNA-binding and transcriptional activity. Interacts
CC with NPAS2, ARNTL/BMAL1 and CLOCK. Interacts with BCAS3. Interacts
CC with CEBPB (PubMed:17301242). Interacts with NR4A3 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q9JHD1,
CC ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:10766811,
CC ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:11931765,
CC ECO:0000269|PubMed:12486002, ECO:0000269|PubMed:14645221,
CC ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:15273251,
CC ECO:0000269|PubMed:16887930, ECO:0000269|PubMed:17226766,
CC ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:17505058,
CC ECO:0000269|PubMed:17707232, ECO:0000269|PubMed:8684459,
CC ECO:0000269|PubMed:9296499, ECO:0000269|PubMed:9346901,
CC ECO:0000269|PubMed:9707565}.
CC -!- INTERACTION:
CC P03255:- (xeno); NbExp=3; IntAct=EBI-477430, EBI-2603114;
CC P03255-2:- (xeno); NbExp=3; IntAct=EBI-477430, EBI-6859460;
CC O60566:BUB1B; NbExp=14; IntAct=EBI-477430, EBI-1001438;
CC Q92793:CREBBP; NbExp=4; IntAct=EBI-477430, EBI-81215;
CC P03129:E7 (xeno); NbExp=3; IntAct=EBI-477430, EBI-866453;
CC Q96KQ7:EHMT2; NbExp=3; IntAct=EBI-477430, EBI-744366;
CC Q09472:EP300; NbExp=2; IntAct=EBI-477430, EBI-447295;
CC Q16665:HIF1A; NbExp=2; IntAct=EBI-477430, EBI-447269;
CC P02299:His3:CG33854 (xeno); NbExp=2; IntAct=EBI-477430, EBI-522090;
CC P84040:His4:CG33909 (xeno); NbExp=2; IntAct=EBI-477430, EBI-185028;
CC Q96EB6:SIRT1; NbExp=3; IntAct=EBI-477430, EBI-1802965;
CC Q8IXJ6:SIRT2; NbExp=4; IntAct=EBI-477430, EBI-477232;
CC Q16594:TAF9; NbExp=3; IntAct=EBI-477430, EBI-712521;
CC O88898-2:Tp63 (xeno); NbExp=3; IntAct=EBI-477430, EBI-2338228;
CC Q15672:TWIST1; NbExp=2; IntAct=EBI-477430, EBI-1797287;
CC P22415:USF1; NbExp=5; IntAct=EBI-477430, EBI-1054489;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed but most abundant in
CC heart and skeletal muscle. {ECO:0000269|PubMed:8684459}.
CC -!- DOMAIN: The bromodomain mediates binding to HIV-1 Tat.
CC -!- SIMILARITY: Belongs to the acetyltransferase family. GCN5
CC subfamily. {ECO:0000305}.
CC -!- SIMILARITY: Contains 1 bromo domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00035}.
CC -!- SIMILARITY: Contains 1 N-acetyltransferase domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00532}.
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DR EMBL; U57317; AAC50890.2; -; mRNA.
DR EMBL; BC060823; AAH60823.1; -; mRNA.
DR EMBL; BC070075; AAH70075.1; -; mRNA.
DR CCDS; CCDS2634.1; -.
DR PIR; S71788; S71788.
DR RefSeq; NP_003875.3; NM_003884.4.
DR UniGene; Hs.533055; -.
DR PDB; 1CM0; X-ray; 2.30 A; A/B=493-658.
DR PDB; 1JM4; NMR; -; B=719-832.
DR PDB; 1N72; NMR; -; A=719-832.
DR PDB; 1WUG; NMR; -; A=719-832.
DR PDB; 1WUM; NMR; -; A=719-832.
DR PDB; 1ZS5; NMR; -; A=719-832.
DR PDB; 2RNW; NMR; -; A=719-832.
DR PDB; 2RNX; NMR; -; A=719-832.
DR PDB; 3GG3; X-ray; 2.25 A; A/B=715-831.
DR PDB; 4NSQ; X-ray; 2.31 A; A/B/C/D=493-658.
DR PDBsum; 1CM0; -.
DR PDBsum; 1JM4; -.
DR PDBsum; 1N72; -.
DR PDBsum; 1WUG; -.
DR PDBsum; 1WUM; -.
DR PDBsum; 1ZS5; -.
DR PDBsum; 2RNW; -.
DR PDBsum; 2RNX; -.
DR PDBsum; 3GG3; -.
DR PDBsum; 4NSQ; -.
DR ProteinModelPortal; Q92831; -.
DR SMR; Q92831; 493-653, 719-832.
DR BioGrid; 114375; 175.
DR DIP; DIP-29778N; -.
DR IntAct; Q92831; 36.
DR MINT; MINT-150079; -.
DR STRING; 9606.ENSP00000263754; -.
DR BindingDB; Q92831; -.
DR ChEMBL; CHEMBL5500; -.
DR GuidetoPHARMACOLOGY; 2737; -.
DR PhosphoSite; Q92831; -.
DR BioMuta; KAT2B; -.
DR DMDM; 83287776; -.
DR REPRODUCTION-2DPAGE; Q92831; -.
DR MaxQB; Q92831; -.
DR PaxDb; Q92831; -.
DR PRIDE; Q92831; -.
DR Ensembl; ENST00000263754; ENSP00000263754; ENSG00000114166.
DR GeneID; 8850; -.
DR KEGG; hsa:8850; -.
DR UCSC; uc003cbq.3; human.
DR CTD; 8850; -.
DR GeneCards; KAT2B; -.
DR HGNC; HGNC:8638; KAT2B.
DR HPA; CAB004526; -.
DR HPA; HPA055839; -.
DR MIM; 602303; gene.
DR neXtProt; NX_Q92831; -.
DR PharmGKB; PA162392705; -.
DR eggNOG; KOG1472; Eukaryota.
DR eggNOG; COG5076; LUCA.
DR GeneTree; ENSGT00760000119099; -.
DR HOGENOM; HOG000007151; -.
DR InParanoid; Q92831; -.
DR KO; K06062; -.
DR OMA; HEDASNY; -.
DR OrthoDB; EOG7ZKS9B; -.
DR PhylomeDB; Q92831; -.
DR TreeFam; TF105399; -.
DR BRENDA; 2.3.1.48; 2681.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3214847; HATs acetylate histones.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR ChiTaRS; KAT2B; human.
DR EvolutionaryTrace; Q92831; -.
DR GeneWiki; PCAF; -.
DR GenomeRNAi; 8850; -.
DR NextBio; 33221; -.
DR PRO; PR:Q92831; -.
DR Proteomes; UP000005640; Chromosome 3.
DR Bgee; Q92831; -.
DR CleanEx; HS_KAT2B; -.
DR Genevisible; Q92831; HS.
DR GO; GO:0031672; C:A band; IEA:Ensembl.
DR GO; GO:0042641; C:actomyosin; IEA:Ensembl.
DR GO; GO:0005671; C:Ada2/Gcn5/Ada3 transcription activator complex; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031674; C:I band; IEA:Ensembl.
DR GO; GO:0000776; C:kinetochore; IEA:Ensembl.
DR GO; GO:0000790; C:nuclear chromatin; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000125; C:PCAF complex; NAS:UniProtKB.
DR GO; GO:0016407; F:acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0004402; F:histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0004468; F:lysine N-acetyltransferase activity, acting on acetyl phosphate as donor; IDA:UniProtKB.
DR GO; GO:0032403; F:protein complex binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription cofactor activity; IPI:UniProtKB.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0007050; P:cell cycle arrest; TAS:ProtInc.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; TAS:Reactome.
DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:BHF-UCL.
DR GO; GO:0043970; P:histone H3-K9 acetylation; IEA:Ensembl.
DR GO; GO:0018393; P:internal peptidyl-lysine acetylation; IDA:UniProtKB.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0018076; P:N-terminal peptidyl-lysine acetylation; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0018394; P:peptidyl-lysine acetylation; IDA:BHF-UCL.
DR GO; GO:0035563; P:positive regulation of chromatin binding; IEA:Ensembl.
DR GO; GO:0035948; P:positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0071442; P:positive regulation of histone H3-K14 acetylation; IEA:Ensembl.
DR GO; GO:2000617; P:positive regulation of histone H3-K9 acetylation; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR GO; GO:0045909; P:positive regulation of vasodilation; IEA:Ensembl.
DR GO; GO:0006473; P:protein acetylation; TAS:ProtInc.
DR GO; GO:0010835; P:regulation of protein ADP-ribosylation; IDA:BHF-UCL.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006360; P:transcription from RNA polymerase I promoter; TAS:Reactome.
DR GO; GO:0006361; P:transcription initiation from RNA polymerase I promoter; TAS:Reactome.
DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR Gene3D; 1.20.920.10; -; 1.
DR Gene3D; 3.40.630.30; -; 1.
DR InterPro; IPR016181; Acyl_CoA_acyltransferase.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR000182; GNAT_dom.
DR InterPro; IPR016376; Hist_acetylase_PCAF.
DR InterPro; IPR009464; PCAF_N.
DR Pfam; PF13508; Acetyltransf_7; 1.
DR Pfam; PF00439; Bromodomain; 1.
DR Pfam; PF06466; PCAF_N; 1.
DR PIRSF; PIRSF003048; Histone_acetylase_PCAF; 1.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00297; BROMO; 1.
DR SUPFAM; SSF47370; SSF47370; 1.
DR SUPFAM; SSF55729; SSF55729; 1.
DR PROSITE; PS00633; BROMODOMAIN_1; 1.
DR PROSITE; PS50014; BROMODOMAIN_2; 1.
DR PROSITE; PS51186; GNAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Acyltransferase; Biological rhythms;
KW Bromodomain; Cell cycle; Complete proteome; Host-virus interaction;
KW Nucleus; Polymorphism; Reference proteome; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1 832 Histone acetyltransferase KAT2B.
FT /FTId=PRO_0000211208.
FT DOMAIN 503 651 N-acetyltransferase.
FT {ECO:0000250|UniProtKB:Q92830,
FT ECO:0000255|PROSITE-ProRule:PRU00532}.
FT DOMAIN 740 810 Bromo. {ECO:0000255|PROSITE-
FT ProRule:PRU00035, ECO:0000305}.
FT REGION 574 576 Acetyl-CoA binding.
FT {ECO:0000269|PubMed:10393169}.
FT REGION 581 587 Acetyl-CoA binding.
FT {ECO:0000269|PubMed:10393169}.
FT REGION 612 615 Acetyl-CoA binding.
FT {ECO:0000269|PubMed:10393169}.
FT ACT_SITE 570 570 Proton donor/acceptor.
FT {ECO:0000303|PubMed:10393169}.
FT VARIANT 386 386 N -> S (in dbSNP:rs17006625).
FT /FTId=VAR_034372.
FT MUTAGEN 752 752 V->A: Reduced acetyl-lysine binding.
FT {ECO:0000269|PubMed:10365964}.
FT MUTAGEN 760 760 Y->A: Reduced acetyl-lysine binding.
FT {ECO:0000269|PubMed:10365964}.
FT MUTAGEN 802 802 Y->A: Reduced acetyl-lysine binding.
FT {ECO:0000269|PubMed:10365964}.
FT MUTAGEN 809 809 Y->A: Complete loss of acetyl-lysine
FT binding. {ECO:0000269|PubMed:10365964}.
FT CONFLICT 804 805 PP -> AA (in Ref. 1; AAC50890).
FT {ECO:0000305}.
FT STRAND 494 499 {ECO:0000244|PDB:1CM0}.
FT STRAND 503 505 {ECO:0000244|PDB:1CM0}.
FT HELIX 509 525 {ECO:0000244|PDB:1CM0}.
FT HELIX 531 538 {ECO:0000244|PDB:1CM0}.
FT STRAND 543 550 {ECO:0000244|PDB:1CM0}.
FT STRAND 553 563 {ECO:0000244|PDB:1CM0}.
FT TURN 564 567 {ECO:0000244|PDB:1CM0}.
FT STRAND 568 576 {ECO:0000244|PDB:1CM0}.
FT HELIX 578 580 {ECO:0000244|PDB:1CM0}.
FT STRAND 582 584 {ECO:0000244|PDB:1CM0}.
FT HELIX 585 599 {ECO:0000244|PDB:1CM0}.
FT STRAND 604 609 {ECO:0000244|PDB:1CM0}.
FT TURN 611 613 {ECO:0000244|PDB:1CM0}.
FT HELIX 614 618 {ECO:0000244|PDB:1CM0}.
FT TURN 619 621 {ECO:0000244|PDB:1CM0}.
FT STRAND 623 625 {ECO:0000244|PDB:1CM0}.
FT HELIX 630 633 {ECO:0000244|PDB:1CM0}.
FT STRAND 644 649 {ECO:0000244|PDB:1CM0}.
FT HELIX 727 741 {ECO:0000244|PDB:3GG3}.
FT STRAND 742 744 {ECO:0000244|PDB:1WUM}.
FT HELIX 746 748 {ECO:0000244|PDB:3GG3}.
FT HELIX 754 756 {ECO:0000244|PDB:3GG3}.
FT STRAND 757 759 {ECO:0000244|PDB:1ZS5}.
FT HELIX 760 763 {ECO:0000244|PDB:3GG3}.
FT STRAND 764 766 {ECO:0000244|PDB:1JM4}.
FT HELIX 770 778 {ECO:0000244|PDB:3GG3}.
FT HELIX 785 802 {ECO:0000244|PDB:3GG3}.
FT STRAND 805 807 {ECO:0000244|PDB:1WUG}.
FT HELIX 808 826 {ECO:0000244|PDB:3GG3}.
FT STRAND 828 830 {ECO:0000244|PDB:1N72}.
SQ SEQUENCE 832 AA; 93013 MW; 72F516E8BC00CC0C CRC64;
MSEAGGAGPG GCGAGAGAGA GPGALPPQPA ALPPAPPQGS PCAAAAGGSG ACGPATAVAA
AGTAEGPGGG GSARIAVKKA QLRSAPRAKK LEKLGVYSAC KAEESCKCNG WKNPNPSPTP
PRADLQQIIV SLTESCRSCS HALAAHVSHL ENVSEEEMNR LLGIVLDVEY LFTCVHKEED
ADTKQVYFYL FKLLRKSILQ RGKPVVEGSL EKKPPFEKPS IEQGVNNFVQ YKFSHLPAKE
RQTIVELAKM FLNRINYWHL EAPSQRRLRS PNDDISGYKE NYTRWLCYCN VPQFCDSLPR
YETTQVFGRT LLRSVFTVMR RQLLEQARQE KDKLPLEKRT LILTHFPKFL SMLEEEVYSQ
NSPIWDQDFL SASSRTSQLG IQTVINPPPV AGTISYNSTS SSLEQPNAGS SSPACKASSG
LEANPGEKRK MTDSHVLEEA KKPRVMGDIP MELINEVMST ITDPAAMLGP ETNFLSAHSA
RDEAARLEER RGVIEFHVVG NSLNQKPNKK ILMWLVGLQN VFSHQLPRMP KEYITRLVFD
PKHKTLALIK DGRVIGGICF RMFPSQGFTE IVFCAVTSNE QVKGYGTHLM NHLKEYHIKH
DILNFLTYAD EYAIGYFKKQ GFSKEIKIPK TKYVGYIKDY EGATLMGCEL NPRIPYTEFS
VIIKKQKEII KKLIERKQAQ IRKVYPGLSC FKDGVRQIPI ESIPGIRETG WKPSGKEKSK
EPRDPDQLYS TLKSILQQVK SHQSAWPFME PVKRTEAPGY YEVIRFPMDL KTMSERLKNR
YYVSKKLFMA DLQRVFTNCK EYNPPESEYY KCANILEKFF FSKIKEAGLI DK
//
ID LCORL_HUMAN Reviewed; 602 AA.
AC Q8N3X6; Q96NK1;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 4.
DT 11-NOV-2015, entry version 103.
DE RecName: Full=Ligand-dependent nuclear receptor corepressor-like protein;
DE Short=LCoR-like protein;
GN Name=LCORL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION.
RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F.,
RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y.,
RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core
RT fucosylated glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
CC -!- FUNCTION: May act as transcription activator that binds DNA
CC elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3'. May play
CC a role in spermatogenesis (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P43360:MAGEA6; NbExp=3; IntAct=EBI-7138654, EBI-1045155;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
CC ProRule:PRU00320}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N3X6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N3X6-2; Sequence=VSP_029287;
CC Name=3;
CC IsoId=Q8N3X6-3; Sequence=VSP_029288, VSP_029289;
CC -!- SIMILARITY: Contains 1 HTH psq-type DNA-binding domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00320}.
CC -!- CAUTION: A report observed N-glycosylation at Asn-493
CC (PubMed:19139490). However, as the protein is predicted to act as
CC a DNA-binding transcription activator, additional evidences are
CC required to confirm this result. {ECO:0000305|PubMed:19139490}.
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DR EMBL; AK055258; BAB70892.1; -; mRNA.
DR EMBL; AC005768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079399; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471069; EAW92786.1; -; Genomic_DNA.
DR EMBL; BC037322; AAH37322.3; -; mRNA.
DR CCDS; CCDS3425.1; -. [Q8N3X6-3]
DR CCDS; CCDS54749.1; -. [Q8N3X6-1]
DR RefSeq; NP_001159611.1; NM_001166139.1. [Q8N3X6-1]
DR RefSeq; NP_710153.2; NM_153686.7. [Q8N3X6-3]
DR UniGene; Hs.446201; -.
DR UniGene; Hs.677572; -.
DR ProteinModelPortal; Q8N3X6; -.
DR SMR; Q8N3X6; 522-579.
DR BioGrid; 129025; 2.
DR IntAct; Q8N3X6; 2.
DR MINT; MINT-8247449; -.
DR STRING; 9606.ENSP00000371661; -.
DR PhosphoSite; Q8N3X6; -.
DR BioMuta; LCORL; -.
DR DMDM; 160395582; -.
DR MaxQB; Q8N3X6; -.
DR PaxDb; Q8N3X6; -.
DR PRIDE; Q8N3X6; -.
DR DNASU; 254251; -.
DR Ensembl; ENST00000326877; ENSP00000317566; ENSG00000178177. [Q8N3X6-3]
DR Ensembl; ENST00000382226; ENSP00000371661; ENSG00000178177. [Q8N3X6-1]
DR GeneID; 254251; -.
DR KEGG; hsa:254251; -.
DR UCSC; uc003gpq.3; human. [Q8N3X6-3]
DR UCSC; uc021xmr.1; human. [Q8N3X6-1]
DR CTD; 254251; -.
DR GeneCards; LCORL; -.
DR HGNC; HGNC:30776; LCORL.
DR HPA; HPA028794; -.
DR HPA; HPA028795; -.
DR HPA; HPA060033; -.
DR MIM; 611799; gene.
DR neXtProt; NX_Q8N3X6; -.
DR PharmGKB; PA145148507; -.
DR eggNOG; KOG4565; Eukaryota.
DR eggNOG; ENOG4111GCI; LUCA.
DR GeneTree; ENSGT00520000055615; -.
DR HOGENOM; HOG000253915; -.
DR HOVERGEN; HBG108084; -.
DR InParanoid; Q8N3X6; -.
DR OMA; YKVKERS; -.
DR OrthoDB; EOG7VHSXQ; -.
DR PhylomeDB; Q8N3X6; -.
DR TreeFam; TF319589; -.
DR ChiTaRS; LCORL; human.
DR GenomeRNAi; 254251; -.
DR NextBio; 92303; -.
DR PRO; PR:Q8N3X6; -.
DR Proteomes; UP000005640; Chromosome 4.
DR Bgee; Q8N3X6; -.
DR CleanEx; HS_LCORL; -.
DR ExpressionAtlas; Q8N3X6; baseline and differential.
DR Genevisible; Q8N3X6; HS.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IEA:Ensembl.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR007889; HTH_Psq.
DR Pfam; PF05225; HTH_psq; 2.
DR SUPFAM; SSF46689; SSF46689; 2.
DR PROSITE; PS50960; HTH_PSQ; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Complete proteome; DNA-binding;
KW Nucleus; Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1 602 Ligand-dependent nuclear receptor
FT corepressor-like protein.
FT /FTId=PRO_0000310463.
FT DOMAIN 516 568 HTH psq-type. {ECO:0000255|PROSITE-
FT ProRule:PRU00320}.
FT DNA_BIND 544 564 H-T-H motif. {ECO:0000255|PROSITE-
FT ProRule:PRU00320}.
FT COMPBIAS 9 31 Ala-rich.
FT VAR_SEQ 1 389 Missing (in isoform 2).
FT {ECO:0000303|PubMed:14702039}.
FT /FTId=VSP_029287.
FT VAR_SEQ 260 318 RLHRNREDYVERSAEFADGLLSKALKDIQSGALDINKAGIL
FT YGIPQKTLLLHLEALPAG -> MLQVKTDEKLNVSDENTAS
FT CPLSPIKMCLNRPIEWNLNLTTASLTSCTVHNQNLKSEEK
FT (in isoform 3).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_029288.
FT VAR_SEQ 319 602 Missing (in isoform 3).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_029289.
FT CONFLICT 407 407 N -> S (in Ref. 1; BAB70892).
FT {ECO:0000305}.
SQ SEQUENCE 602 AA; 66964 MW; 05245F999E5A61D7 CRC64;
MDKGRERMAA AAAAAAAAAA AAQCRSPRCA AERRGFRREL DSWRHRLMHC VGFESILEGL
YGPRLRRDLS LFEDCEPEEL TDWSMDEKCS FCNLQREAVS DCIPSLDSSQ STPTEELSSQ
GQSNTDKIEC QAENYLNALF RKKDLPQNCD PNIPLVAQEL MKKMIRQFAI EYISKSGKTQ
ENRNGSIGPS IVCKSIQMNQ AENSLQEEQE GPLDLTVNRM QEQNTQQGDG VLDLSTKKTS
IKSEESSICD PSSENSVAGR LHRNREDYVE RSAEFADGLL SKALKDIQSG ALDINKAGIL
YGIPQKTLLL HLEALPAGKP ASFKNKTRDF HDSYSYKDSK ETCAVLQKVA LWARAQAERT
EKSKLNLLET SEIKFPTAST YLHQLTLQKM VTQFKEKNES LQYETSNPTV QLKIPQLRVS
SVSKSQPDGS GLLDVMYQVS KTSSVLEGSA LQKLKNILPK QNKIECSGPV THSSVDSYFL
HGDLSPLCLN SKNGTVDGTS ENTEDGLDRK DSKQPRKKRG RYRQYDHEIM EEAIAMVMSG
KMSVSKAQGI YGVPHSTLEY KVKERSGTLK TPPKKKLRLP DTGLYNMTDS GTGSCKNSSK
PV
//
ID LCOR_HUMAN Reviewed; 433 AA.
AC Q96JN0; D3DR47; Q5VW16; Q7Z723; Q86T32; Q86T33; Q8N3L6;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 11-NOV-2015, entry version 103.
DE RecName: Full=Ligand-dependent corepressor;
DE Short=LCoR;
DE AltName: Full=Mblk1-related protein 2;
GN Name=LCOR; Synonyms=KIAA1795, MLR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, and Skeletal muscle;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, INTERACTION WITH CTBP1; ESR1; ESR2; HDAC3 AND HDAC6,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF 56-LEU-LEU-57, AND TISSUE
RP SPECIFICITY.
RX PubMed=12535528; DOI=10.1016/S1097-2765(03)00014-5;
RA Fernandes I., Bastien Y., Wai T., Nygard K., Lin R., Cormier O.,
RA Lee H.S., Eng F., Bertos N.R., Pelletier N., Mader S., Han V.K.M.,
RA Yang X.-J., White J.H.;
RT "Ligand-dependent nuclear receptor corepressor LCoR functions by
RT histone deacetylase-dependent and -independent mechanisms.";
RL Mol. Cell 11:139-150(2003).
RN [7]
RP IDENTIFICATION IN A COREPRESSOR COMPLEX, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=12700765; DOI=10.1038/nature01550;
RA Shi Y., Sawada J., Sui G., Affar E.B., Whetstine J.R., Lan F.,
RA Ogawa H., Luke M.P.-S., Nakatani Y., Shi Y.;
RT "Coordinated histone modifications mediated by a CtBP co-repressor
RT complex.";
RL Nature 422:735-738(2003).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63 AND SER-249, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP STRUCTURE BY NMR OF 343-405.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structures of the HTH domain of human LCOR protein.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: May act as transcription activator that binds DNA
CC elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3' (By
CC similarity). Repressor of ligand-dependent transcription
CC activation by target nuclear receptors. Repressor of ligand-
CC dependent transcription activation by ESR1, ESR2, NR3C1, PGR,
CC RARA, RARB, RARG, RXRA and VDR. {ECO:0000250,
CC ECO:0000269|PubMed:12535528}.
CC -!- SUBUNIT: Interacts with ESR1 and ESR2 in the presence of
CC estradiol. Interacts with CTBP1, HDAC3 and HDAC6. Component of a
CC large corepressor complex that contains about 20 proteins,
CC including CTBP1, CTBP2, HDAC1 and HDAC2.
CC {ECO:0000269|PubMed:12535528, ECO:0000269|PubMed:12700765}.
CC -!- INTERACTION:
CC P56545:CTBP2; NbExp=3; IntAct=EBI-8833163, EBI-741533;
CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-8833163, EBI-10171902;
CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-8833163, EBI-618309;
CC Q13077:TRAF1; NbExp=3; IntAct=EBI-8833163, EBI-359224;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
CC ProRule:PRU00320, ECO:0000269|PubMed:12535528}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96JN0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96JN0-2; Sequence=VSP_018585, VSP_018586;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12535528}.
CC -!- SIMILARITY: Contains 1 HTH psq-type DNA-binding domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00320}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47424.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB058698; BAB47424.1; ALT_INIT; mRNA.
DR EMBL; AL834245; CAD38921.2; -; mRNA.
DR EMBL; AL832106; CAD91159.1; -; mRNA.
DR EMBL; AL832044; CAD91160.1; -; mRNA.
DR EMBL; AL442123; CAH70915.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49963.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49965.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49966.1; -; Genomic_DNA.
DR EMBL; BC053359; AAH53359.1; -; mRNA.
DR CCDS; CCDS53561.1; -. [Q96JN0-2]
DR CCDS; CCDS7451.1; -. [Q96JN0-1]
DR RefSeq; NP_001164236.1; NM_001170765.1. [Q96JN0-1]
DR RefSeq; NP_001164237.1; NM_001170766.1. [Q96JN0-2]
DR RefSeq; NP_115816.2; NM_032440.3. [Q96JN0-1]
DR RefSeq; XP_006718097.1; XM_006718034.2. [Q96JN0-1]
DR UniGene; Hs.745068; -.
DR PDB; 2COB; NMR; -; A=343-405.
DR PDBsum; 2COB; -.
DR ProteinModelPortal; Q96JN0; -.
DR SMR; Q96JN0; 346-405.
DR BioGrid; 124093; 23.
DR IntAct; Q96JN0; 4.
DR STRING; 9606.ENSP00000348298; -.
DR PhosphoSite; Q96JN0; -.
DR BioMuta; LCOR; -.
DR DMDM; 108936028; -.
DR MaxQB; Q96JN0; -.
DR PaxDb; Q96JN0; -.
DR PRIDE; Q96JN0; -.
DR DNASU; 84458; -.
DR Ensembl; ENST00000356016; ENSP00000348298; ENSG00000196233. [Q96JN0-1]
DR Ensembl; ENST00000371097; ENSP00000360138; ENSG00000196233. [Q96JN0-1]
DR Ensembl; ENST00000371103; ENSP00000360144; ENSG00000196233. [Q96JN0-1]
DR Ensembl; ENST00000540664; ENSP00000443431; ENSG00000196233. [Q96JN0-2]
DR GeneID; 84458; -.
DR KEGG; hsa:84458; -.
DR UCSC; uc001kmr.3; human. [Q96JN0-2]
DR UCSC; uc001kms.2; human. [Q96JN0-1]
DR CTD; 84458; -.
DR GeneCards; LCOR; -.
DR HGNC; HGNC:29503; LCOR.
DR HPA; HPA031428; -.
DR HPA; HPA031429; -.
DR MIM; 607698; gene.
DR neXtProt; NX_Q96JN0; -.
DR PharmGKB; PA145148487; -.
DR eggNOG; KOG4565; Eukaryota.
DR eggNOG; ENOG4111GCI; LUCA.
DR GeneTree; ENSGT00520000055615; -.
DR HOVERGEN; HBG079596; -.
DR InParanoid; Q96JN0; -.
DR OMA; HYEFNFS; -.
DR OrthoDB; EOG73RBBB; -.
DR PhylomeDB; Q96JN0; -.
DR TreeFam; TF319589; -.
DR ChiTaRS; LCOR; human.
DR EvolutionaryTrace; Q96JN0; -.
DR GeneWiki; LCOR; -.
DR GenomeRNAi; 84458; -.
DR NextBio; 74251; -.
DR PRO; PR:Q96JN0; -.
DR Proteomes; UP000005640; Chromosome 10.
DR Bgee; Q96JN0; -.
DR CleanEx; HS_LCOR; -.
DR Genevisible; Q96JN0; HS.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IEA:Ensembl.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR007889; HTH_Psq.
DR Pfam; PF05225; HTH_psq; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50960; HTH_PSQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Complete proteome;
KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1 433 Ligand-dependent corepressor.
FT /FTId=PRO_0000236807.
FT DOMAIN 340 392 HTH psq-type. {ECO:0000255|PROSITE-
FT ProRule:PRU00320}.
FT DNA_BIND 368 388 H-T-H motif. {ECO:0000255|PROSITE-
FT ProRule:PRU00320}.
FT MOTIF 53 57 Interaction with nuclear receptors.
FT MOTIF 339 345 Nuclear localization signal.
FT {ECO:0000255}.
FT MOD_RES 63 63 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 249 249 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT VAR_SEQ 405 406 RS -> SG (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_018585.
FT VAR_SEQ 407 433 Missing (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_018586.
FT MUTAGEN 56 57 LL->AA: Loss of estradiol-dependent
FT interaction with ESR1 and ESR2.
FT {ECO:0000269|PubMed:12535528}.
FT CONFLICT 6 6 Q -> P (in Ref. 2; CAD91159).
FT {ECO:0000305}.
FT CONFLICT 321 321 S -> P (in Ref. 2; CAD38921).
FT {ECO:0000305}.
FT HELIX 351 362 {ECO:0000244|PDB:2COB}.
FT HELIX 368 375 {ECO:0000244|PDB:2COB}.
FT HELIX 379 389 {ECO:0000244|PDB:2COB}.
FT TURN 390 393 {ECO:0000244|PDB:2COB}.
SQ SEQUENCE 433 AA; 47007 MW; 5F934FE687417740 CRC64;
MQRMIQQFAA EYTSKNSSTQ DPSQPNSTKN QSLPKASPVT TSPTAATTQN PVLSKLLMAD
QDSPLDLTVR KSQSEPSEQD GVLDLSTKKS PCAGSTSLSH SPGCSSTQGN GRPGRPSQYR
PDGLRSGDGV PPRSLQDGTR EGFGHSTSLK VPLARSLQIS EELLSRNQLS TAASLGPSGL
QNHGQHLILS REASWAKPHY EFNLSRMKFR GNGALSNISD LPFLAENSAF PKMALQAKQD
GKKDVSHSSP VDLKIPQVRG MDLSWESRTG DQYSYSSLVM GSQTESALSK KLRAILPKQS
RKSMLDAGPD SWGSDAEQST SGQPYPTSDQ EGDPGSKQPR KKRGRYRQYN SEILEEAISV
VMSGKMSVSK AQSIYGIPHS TLEYKVKERL GTLKNPPKKK MKLMRSEGPD VSVKIELDPQ
GEAAQSANES KNE
//
ID MDS1_HUMAN Reviewed; 169 AA.
AC Q13465; Q13466; Q6FH90;
DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 11-NOV-2015, entry version 110.
DE RecName: Full=MDS1 and EVI1 complex locus protein MDS1;
DE AltName: Full=Myelodysplasia syndrome 1 protein;
DE AltName: Full=Myelodysplasia syndrome-associated protein 1;
GN Name=MECOM; Synonyms=MDS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney, and Pancreas;
RX PubMed=8643684; DOI=10.1073/pnas.93.4.1642;
RA Fears S., Mathieu C., Zeleznik-Le N., Huang S., Rowley J.D.,
RA Nucifora G.;
RT "Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well
RT as in myeloid leukemia and produces a new member of the PR domain
RT family.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1642-1647(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- INTERACTION:
CC Q5R372-2:RABGAP1L; NbExp=3; IntAct=EBI-8475192, EBI-10692254;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6;
CC Name=3; Synonyms=Mds1;
CC IsoId=Q13465-1; Sequence=Displayed;
CC Note=Produced by alternative promoter usage.;
CC Name=1; Synonyms=Long, Evi-1a;
CC IsoId=Q03112-1; Sequence=External;
CC Name=2; Synonyms=Evi-1c, Mds1/Evi1;
CC IsoId=Q03112-3; Sequence=External;
CC Note=Produced by alternative promoter usage. Contains an
CC additional SET domain at positions 79-194. Unable to form
CC homooligomers, to interact with CTBP1 and SMAD3 and to repress
CC TGF-beta signaling. Contains a glycyl lysine isopeptide
CC (Lys-Gly) (interchain with G-Cter in SUMO2) at position 190.;
CC Name=4;
CC IsoId=Q03112-4; Sequence=External;
CC Note=Contains a glycyl lysine isopeptide (Lys-Gly) (interchain
CC with G-Cter in SUMO2) at position 66.;
CC Name=5;
CC IsoId=Q03112-5; Sequence=External;
CC Name=6;
CC IsoId=Q03112-6; Sequence=External;
CC -!- DISEASE: Note=A chromosomal aberration involving MDS1 is found in
CC a form of acute myeloid leukemia (AML). Translocation t(3;21) with
CC AML1.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/EVI103q26ID19.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U43292; AAB05839.1; -; mRNA.
DR EMBL; U43293; AAB05840.1; ALT_SEQ; mRNA.
DR EMBL; CR541866; CAG46664.1; -; mRNA.
DR EMBL; CR541886; CAG46684.1; -; mRNA.
DR EMBL; CH471052; EAW78549.1; -; Genomic_DNA.
DR EMBL; BC069498; AAH69498.1; -; mRNA.
DR RefSeq; NP_004982.2; NM_004991.3.
DR UniGene; Hs.744090; -.
DR ProteinModelPortal; Q13465; -.
DR SMR; Q13465; 47-130.
DR BioGrid; 108423; 21.
DR IntAct; Q13465; 3.
DR MINT; MINT-8417693; -.
DR PhosphoSite; Q13465; -.
DR MaxQB; Q13465; -.
DR PRIDE; Q13465; -.
DR DNASU; 2122; -.
DR GeneID; 2122; -.
DR UCSC; uc011bpl.1; human. [Q13465-1]
DR CTD; 2122; -.
DR GeneCards; MECOM; -.
DR HGNC; HGNC:3498; MECOM.
DR MIM; 600049; gene.
DR neXtProt; NX_Q13465; -.
DR PharmGKB; PA27912; -.
DR PharmGKB; PA30722; -.
DR HOVERGEN; HBG031707; -.
DR PhylomeDB; Q13465; -.
DR ChiTaRS; MECOM; human.
DR GenomeRNAi; 2122; -.
DR NextBio; 8579; -.
DR Proteomes; UP000005640; Unplaced.
DR CleanEx; HS_MDS1; -.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:GOC.
DR InterPro; IPR026710; MDS1.
DR PANTHER; PTHR21652; PTHR21652; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Alternative splicing;
KW Chromosomal rearrangement; Complete proteome; Polymorphism;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1 169 MDS1 and EVI1 complex locus protein MDS1.
FT /FTId=PRO_0000096338.
FT VARIANT 120 120 P -> S (in dbSNP:rs7622799).
FT /FTId=VAR_051183.
SQ SEQUENCE 169 AA; 18696 MW; 3EE36C8ACB62EFFE CRC64;
MRSKGRARKL ATNNECVYGN YPEIPLEEMP DADGVASTPS LNIQEPCSPA TSSEAFTPKE
GSPYKAPIYI PDDIPIPAEF ELRESNMPGA GLGIWTKRKI EVGEKFGPYV GEQRSNLKDP
SYGWEVHLPR SRRVSVHSWL YLGKRSSDVG IAFSQADVYM PGLQCAFLS
//
ID NOL4L_HUMAN Reviewed; 436 AA.
AC Q96MY1; Q5JYB7; Q6P0Y4; Q9BR34; Q9NQF6;
DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2003, sequence version 2.
DT 11-NOV-2015, entry version 111.
DE RecName: Full=Nucleolar protein 4-like;
GN Name=NOL4L; Synonyms=C20orf112, C20orf113;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Neuron;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
CC -!- INTERACTION:
CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-6660790, EBI-10171858;
CC P56545:CTBP2; NbExp=3; IntAct=EBI-6660790, EBI-741533;
CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-6660790, EBI-10171902;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96MY1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96MY1-2; Sequence=VSP_014667, VSP_014668;
CC Note=No experimental confirmation available.;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AK056286; BAB71138.1; -; mRNA.
DR EMBL; AL034550; CAI42261.1; -; Genomic_DNA.
DR EMBL; BC065370; AAH65370.1; -; mRNA.
DR CCDS; CCDS13202.1; -. [Q96MY1-1]
DR RefSeq; NP_001243727.1; NM_001256798.1.
DR RefSeq; NP_542183.2; NM_080616.4. [Q96MY1-1]
DR RefSeq; XP_005260345.1; XM_005260288.1. [Q96MY1-1]
DR RefSeq; XP_005260346.1; XM_005260289.3. [Q96MY1-1]
DR UniGene; Hs.516978; -.
DR UniGene; Hs.729596; -.
DR ProteinModelPortal; Q96MY1; -.
DR BioGrid; 126651; 5.
DR IntAct; Q96MY1; 4.
DR STRING; 9606.ENSP00000352704; -.
DR PhosphoSite; Q96MY1; -.
DR BioMuta; C20orf112; -.
DR DMDM; 28212212; -.
DR MaxQB; Q96MY1; -.
DR PaxDb; Q96MY1; -.
DR PRIDE; Q96MY1; -.
DR DNASU; 140688; -.
DR Ensembl; ENST00000359676; ENSP00000352704; ENSG00000197183. [Q96MY1-1]
DR GeneID; 140688; -.
DR KEGG; hsa:140688; -.
DR UCSC; uc002wxu.5; human. [Q96MY1-1]
DR CTD; 140688; -.
DR GeneCards; NOL4L; -.
DR H-InvDB; HIX0015727; -.
DR H-InvDB; HIX0015728; -.
DR HGNC; HGNC:16106; NOL4L.
DR HPA; HPA041768; -.
DR HPA; HPA043600; -.
DR neXtProt; NX_Q96MY1; -.
DR PharmGKB; PA25652; -.
DR eggNOG; ENOG410IHZD; Eukaryota.
DR eggNOG; ENOG410YIBB; LUCA.
DR GeneTree; ENSGT00390000017363; -.
DR HOGENOM; HOG000220856; -.
DR HOVERGEN; HBG031438; -.
DR InParanoid; Q96MY1; -.
DR PhylomeDB; Q96MY1; -.
DR TreeFam; TF325594; -.
DR ChiTaRS; C20orf112; human.
DR GenomeRNAi; 140688; -.
DR NextBio; 84231; -.
DR PRO; PR:Q96MY1; -.
DR Proteomes; UP000005640; Chromosome 20.
DR Bgee; Q96MY1; -.
DR CleanEx; HS_C20orf112; -.
DR ExpressionAtlas; Q96MY1; baseline and differential.
DR Genevisible; Q96MY1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR InterPro; IPR026746; NOL4L.
DR PANTHER; PTHR12449:SF19; PTHR12449:SF19; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1 436 Nucleolar protein 4-like.
FT /FTId=PRO_0000079456.
FT COMPBIAS 161 169 Poly-Asp.
FT MOD_RES 130 130 Phosphoserine.
FT {ECO:0000244|PubMed:18669648}.
FT VAR_SEQ 382 398 TPTPSSTSTSRPVPTAQ -> SALSGEPPTRRWGCSSV
FT (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_014667.
FT VAR_SEQ 399 436 Missing (in isoform 2).
FT {ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_014668.
FT CONFLICT 215 215 K -> E (in Ref. 1; BAB71138).
FT {ECO:0000305}.
SQ SEQUENCE 436 AA; 47215 MW; 139A07537D875DF8 CRC64;
MSDSTWMSAD PHLASSLSPS QDERMRSPQN LHSQEDDDSS SESGSGNGSS TLNPSTSSST
QGDPAFPEMN GNGAVAPMDF TTAAEDQPIN LCDKLPPATA LGTASYPSDG CGADGLRSRV
KYGVKTTPES PPYSSGSYDS IKTEVSGCPE DLTVGRAPTA DDDDDDHDDH EDNDKMNDSE
GMDPERLKAF NMFVRLFVDE NLDRMVPISK QPKEKIQAII ESCSRQFPEF QERARKRIRT
YLKSCRRMKK NGMEMTRPTP PHLTSAMAEN ILAAACESET RKAAKRMRLE IYQSSQDEPI
ALDKQHSRDS AAITHSTYSL PASSYSQDPV YANGGLNYSY RGYGALSSNL QPPASLQTGN
HSNGPTDLSM KGGASTTSTT PTPTPSSTST SRPVPTAQLS PTEISAVRQL IAGYRESAAF
LLRSADELEN LILQQN
//
ID NRIP1_HUMAN Reviewed; 1158 AA.
AC P48552; Q8IWE8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 11-NOV-2015, entry version 140.
DE RecName: Full=Nuclear receptor-interacting protein 1;
DE AltName: Full=Nuclear factor RIP140;
DE AltName: Full=Receptor-interacting protein 140;
GN Name=NRIP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ESR1,
RP SUBCELLULAR LOCATION, AND VARIANT GLY-448.
RC TISSUE=Mammary gland;
RX PubMed=7641693;
RA Cavailles V., Dauvois S., L'Horset F., Lopez G., Hoare S.,
RA Kushner P.J., Parker M.G.;
RT "Nuclear factor RIP140 modulates transcriptional activation by the
RT estrogen receptor.";
RL EMBO J. 14:3741-3751(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T.,
RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH NR2C2.
RX PubMed=9556573; DOI=10.1074/jbc.273.18.10948;
RA Yan Z.H., Karam W.G., Staudinger J.L., Medvedev A., Ghanayem B.I.,
RA Jetten A.M.;
RT "Regulation of peroxisome proliferator-activated receptor alpha-
RT induced transactivation by the nuclear orphan receptor TAK1/TR4.";
RL J. Biol. Chem. 273:10948-10957(1998).
RN [5]
RP FUNCTION, AND INTERACTION WITH NR3C1.
RX PubMed=10364267; DOI=10.1074/jbc.274.25.18121;
RA Subramaniam N., Treuter E., Okret S.;
RT "Receptor interacting protein RIP140 inhibits both positive and
RT negative gene regulation by glucocorticoids.";
RL J. Biol. Chem. 274:18121-18127(1999).
RN [6]
RP FUNCTION, INTERACTION WITH CTBP1, MUTAGENESIS OF 440-PRO--LEU-443 AND
RP LYS-446, AND ACETYLATION AT LYS-446.
RX PubMed=11509661; DOI=10.1128/MCB.21.18.6181-6188.2001;
RA Vo N., Fjeld C., Goodman R.H.;
RT "Acetylation of nuclear hormone receptor-interacting protein RIP140
RT regulates binding of the transcriptional corepressor CtBP.";
RL Mol. Cell. Biol. 21:6181-6188(2001).
RN [7]
RP INTERACTION WITH NR3C1 AND YWHAH, IDENTIFICATION IN A COMPLEX WITH
RP NR3C1 AND YWHAH, AND SUBCELLULAR LOCATION.
RX PubMed=11266503; DOI=10.1210/me.15.4.501;
RA Zilliacus J., Holter E., Wakui H., Tazawa H., Treuter E.,
RA Gustafsson J.-A.;
RT "Regulation of glucocorticoid receptor activity by 14-3-3-dependent
RT intracellular relocalization of the corepressor RIP140.";
RL Mol. Endocrinol. 15:501-511(2001).
RN [8]
RP FUNCTION, AND INTERACTION WITH NR3C2.
RX PubMed=11518808; DOI=10.1210/me.15.9.1586;
RA Zennaro M.-C., Souque A., Viengchareun S., Poisson E., Lombes M.;
RT "A new human MR splice variant is a ligand-independent transactivator
RT modulating corticosteroid action.";
RL Mol. Endocrinol. 15:1586-1598(2001).
RN [9]
RP INTERACTION WITH NR3C1, AND SUBCELLULAR LOCATION.
RX PubMed=12773562; DOI=10.1128/MCB.23.12.4187-4198.2003;
RA Tazawa H., Osman W., Shoji Y., Treuter E., Gustafsson J.-A.,
RA Zilliacus J.;
RT "Regulation of subnuclear localization is associated with a mechanism
RT for nuclear receptor corepression by RIP140.";
RL Mol. Cell. Biol. 23:4187-4198(2003).
RN [10]
RP FUNCTION, AND INTERACTION WITH ESR1; FOS AND JUN.
RX PubMed=12554755; DOI=10.1210/me.2002-0324;
RA Teyssier C., Belguise K., Galtier F., Cavailles V., Chalbos D.;
RT "Receptor-interacting protein 140 binds c-Jun and inhibits estradiol-
RT induced activator protein-1 activity by reversing glucocorticoid
RT receptor-interacting protein 1 effect.";
RL Mol. Endocrinol. 17:287-299(2003).
RN [11]
RP INTERACTION WITH CTBP1 AND CTBP2, MUTAGENESIS OF 442-ASP--LEU-443;
RP 567-ASN--LEU-568 AND 948-ASP--LEU-949, AND IDENTIFICATION OF
RP REPRESSION DOMAINS.
RX PubMed=14736873; DOI=10.1074/jbc.M313906200;
RA Christian M., Tullet J.M.A., Parker M.G.;
RT "Characterization of four autonomous repression domains in the
RT corepressor receptor interacting protein 140.";
RL J. Biol. Chem. 279:15645-15651(2004).
RN [12]
RP FUNCTION, INTERACTION WITH CTBP1; CTBP2; HDAC1; HDAC2; HDAC5 AND
RP HDAC6, MUTAGENESIS OF 442-ASP--LEU-443 AND 567-ASN--LEU-568, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15060175; DOI=10.1093/nar/gkh524;
RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P.,
RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.;
RT "Multiple domains of the receptor-interacting protein 140 contribute
RT to transcription inhibition.";
RL Nucleic Acids Res. 32:1957-1966(2004).
RN [13]
RP INTERACTION WITH NR2C2.
RX PubMed=16887930; DOI=10.1074/mcp.M600180-MCP200;
RA Huq M.D., Gupta P., Tsai N.P., Wei L.N.;
RT "Modulation of testicular receptor 4 activity by mitogen-activated
RT protein kinase-mediated phosphorylation.";
RL Mol. Cell. Proteomics 5:2072-2082(2006).
RN [14]
RP INTERACTION WITH ZNF366.
RX PubMed=17085477; DOI=10.1093/nar/gkl875;
RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M.,
RA Jat P., Kindle K.B., Heery D.M., Parker M.G., Buluwela L.,
RA Kamalati T., Ali S.;
RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and
RT histone deacetylases.";
RL Nucleic Acids Res. 34:6126-6136(2006).
RN [15]
RP FUNCTION, INTERACTION WITH RORA, AND INDUCTION.
RX PubMed=21628546; DOI=10.1177/0748730411401579;
RA Poliandri A.H., Gamsby J.J., Christian M., Spinella M.J., Loros J.J.,
RA Dunlap J.C., Parker M.G.;
RT "Modulation of clock gene expression by the transcriptional
RT coregulator receptor interacting protein 140 (RIP140).";
RL J. Biol. Rhythms 26:187-199(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-671 AND
RP SER-807, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-756 AND LYS-1105, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 366-390 IN COMPLEX WITH
RP ESRRG.
RX PubMed=16990259; DOI=10.1074/jbc.M608410200;
RA Wang L., Zuercher W.J., Consler T.G., Lambert M.H., Miller A.B.,
RA Orband-Miller L.A., McKee D.D., Willson T.M., Nolte R.T.;
RT "X-ray crystal structures of the estrogen-related receptor-gamma
RT ligand binding domain in three functional states reveal the molecular
RT basis of small molecule regulation.";
RL J. Biol. Chem. 281:37773-37781(2006).
RN [19]
RP VARIANTS ARG-221; VAL-441; GLY-448; LEU-803 AND PHE-1079.
RX PubMed=16131398; DOI=10.1186/1743-1050-2-11;
RA Caballero V., Ruiz R., Sainz J.A., Cruz M., Lopez-Nevot M.A.,
RA Galan J.J., Real L.M., de Castro F., Lopez-Villaverde V., Ruiz A.;
RT "Preliminary molecular genetic analysis of the receptor interacting
RT protein 140 (RIP140) in women affected by endometriosis.";
RL J. Exp. Clin. Assist. Reprod. 2:11-11(2005).
CC -!- FUNCTION: Modulates transcriptional activation by steroid
CC receptors such as NR3C1, NR3C2 and ESR1. Also modulates
CC transcriptional repression by nuclear hormone receptors. Positive
CC regulator of the circadian clock gene expression: stimulates
CC transcription of ARNTL/BMAL1, CLOCK and CRY1 by acting as a
CC coactivator for RORA and RORC. {ECO:0000269|PubMed:10364267,
CC ECO:0000269|PubMed:11509661, ECO:0000269|PubMed:11518808,
CC ECO:0000269|PubMed:12554755, ECO:0000269|PubMed:15060175,
CC ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:7641693}.
CC -!- SUBUNIT: Interacts with RARA and RXRB homodimers and RARA/RXRB
CC heterodimers in the presence of ligand. Interacts with HDAC1 and
CC HDAC3 via its N-terminal domain. Interacts with NR2C1 (sumoylated
CC form and via the ligand-binding domain); the interaction results
CC in promoting the repressor activity of NR2C1 (By similarity).
CC Interacts with CTBP1, CTBP2, ESR1, HDAC1, HDAC2, HDAC5, HDAC6,
CC NR2C2, NR3C1, NR3C2, YWHAH, JUN and FOS. Found in a complex with
CC both NR3C1 and YWHAH. Interacts with ZNF366. Interacts with RORA.
CC {ECO:0000250|UniProtKB:Q8CBD1, ECO:0000269|PubMed:10364267,
CC ECO:0000269|PubMed:11266503, ECO:0000269|PubMed:11509661,
CC ECO:0000269|PubMed:11518808, ECO:0000269|PubMed:12554755,
CC ECO:0000269|PubMed:12773562, ECO:0000269|PubMed:14736873,
CC ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:16887930,
CC ECO:0000269|PubMed:16990259, ECO:0000269|PubMed:17085477,
CC ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:7641693,
CC ECO:0000269|PubMed:9556573}.
CC -!- INTERACTION:
CC O15145:ARPC3; NbExp=3; IntAct=EBI-746484, EBI-351829;
CC Q8NHQ1:CEP70; NbExp=3; IntAct=EBI-746484, EBI-739624;
CC P26358:DNMT1; NbExp=3; IntAct=EBI-746484, EBI-719459;
CC Q13642:FHL1; NbExp=6; IntAct=EBI-746484, EBI-912547;
CC O15379:HDAC3; NbExp=2; IntAct=EBI-746484, EBI-607682;
CC O95751:LDOC1; NbExp=3; IntAct=EBI-746484, EBI-740738;
CC Q99873:PRMT1; NbExp=4; IntAct=EBI-746484, EBI-78738;
CC P10276:RARA; NbExp=4; IntAct=EBI-746484, EBI-413374;
CC P10276-2:RARA; NbExp=3; IntAct=EBI-746484, EBI-10197061;
CC Q8N895:ZNF366; NbExp=2; IntAct=EBI-746484, EBI-2813661;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11266503,
CC ECO:0000269|PubMed:12773562, ECO:0000269|PubMed:15060175,
CC ECO:0000269|PubMed:7641693}. Note=Localized to discrete foci and
CC redistributes to larger nuclear domains upon binding to ligand-
CC bound NR3C1.
CC -!- INDUCTION: Expressed in a circadian manner in the liver (at
CC protein level). {ECO:0000269|PubMed:21628546}.
CC -!- DOMAIN: Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have
CC different affinities for nuclear receptors. The C-terminal
CC LTKTNPILYYMLQK motif is required for ligand-dependent interaction
CC with RAAR and RXRB homodimers and heterodimers, for the
CC corepressor activity, and for the formation of an HDAC3 complex
CC with RARA/RXRB (By similarity). Contains at least four autonomous
CC repression domains (RD1-4). RD1 functions via a histone
CC deacetylase (HDAC)-independent mechanism, whereas RD2, RD3 and RD4
CC can function by HDAC-dependent or independent mechanisms,
CC depending on cell type. RD2 is dependent on CTBP binding.
CC {ECO:0000250}.
CC -!- PTM: Acetylation regulates its nuclear translocation and
CC corepressive activity (By similarity). Acetylation abolishes
CC interaction with CTBP1. Phosphorylation enhances interaction with
CC YWHAH. {ECO:0000250, ECO:0000269|PubMed:11509661}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NRIP1ID44067ch21q11.html";
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DR EMBL; X84373; CAA59108.1; -; mRNA.
DR EMBL; AF248484; AAF62185.1; -; Genomic_DNA.
DR EMBL; AF127577; AAF35255.1; -; Genomic_DNA.
DR EMBL; AL163207; CAB90396.1; -; Genomic_DNA.
DR EMBL; BC040361; AAH40361.1; -; mRNA.
DR CCDS; CCDS13568.1; -.
DR PIR; S57348; S57348.
DR RefSeq; NP_003480.2; NM_003489.3.
DR RefSeq; XP_005261120.1; XM_005261063.2.
DR RefSeq; XP_005261122.1; XM_005261065.2.
DR RefSeq; XP_011528049.1; XM_011529747.1.
DR RefSeq; XP_011528050.1; XM_011529748.1.
DR RefSeq; XP_011528051.1; XM_011529749.1.
DR RefSeq; XP_011528052.1; XM_011529750.1.
DR RefSeq; XP_011528053.1; XM_011529751.1.
DR RefSeq; XP_011528054.1; XM_011529752.1.
DR UniGene; Hs.155017; -.
DR PDB; 2GPO; X-ray; 1.95 A; C=366-390.
DR PDB; 2GPP; X-ray; 2.60 A; C/D=366-390.
DR PDB; 4S14; X-ray; 3.54 A; C=499-510.
DR PDB; 4S15; X-ray; 1.90 A; C/D=499-510.
DR PDBsum; 2GPO; -.
DR PDBsum; 2GPP; -.
DR PDBsum; 4S14; -.
DR PDBsum; 4S15; -.
DR ProteinModelPortal; P48552; -.
DR BioGrid; 113843; 56.
DR DIP; DIP-5964N; -.
DR IntAct; P48552; 22.
DR MINT; MINT-192711; -.
DR STRING; 9606.ENSP00000327213; -.
DR PhosphoSite; P48552; -.
DR BioMuta; NRIP1; -.
DR DMDM; 9988061; -.
DR MaxQB; P48552; -.
DR PaxDb; P48552; -.
DR PRIDE; P48552; -.
DR DNASU; 8204; -.
DR Ensembl; ENST00000318948; ENSP00000327213; ENSG00000180530.
DR Ensembl; ENST00000400199; ENSP00000383060; ENSG00000180530.
DR Ensembl; ENST00000400202; ENSP00000383063; ENSG00000180530.
DR GeneID; 8204; -.
DR KEGG; hsa:8204; -.
DR UCSC; uc002yjx.2; human.
DR CTD; 8204; -.
DR GeneCards; NRIP1; -.
DR H-InvDB; HIX0027827; -.
DR HGNC; HGNC:8001; NRIP1.
DR HPA; HPA046571; -.
DR HPA; HPA060036; -.
DR MIM; 602490; gene.
DR neXtProt; NX_P48552; -.
DR PharmGKB; PA31780; -.
DR eggNOG; ENOG410IFW7; Eukaryota.
DR eggNOG; ENOG410XPVS; LUCA.
DR GeneTree; ENSGT00390000007999; -.
DR HOGENOM; HOG000236277; -.
DR HOVERGEN; HBG052667; -.
DR InParanoid; P48552; -.
DR KO; K17965; -.
DR OMA; VEKDLRC; -.
DR OrthoDB; EOG7H1JJQ; -.
DR PhylomeDB; P48552; -.
DR TreeFam; TF332210; -.
DR Reactome; R-HSA-1368082; RORA activates gene expression.
DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR Reactome; R-HSA-400253; Circadian Clock.
DR SignaLink; P48552; -.
DR ChiTaRS; NRIP1; human.
DR EvolutionaryTrace; P48552; -.
DR GeneWiki; NRIP1; -.
DR GenomeRNAi; 8204; -.
DR NextBio; 30914; -.
DR PRO; PR:P48552; -.
DR Proteomes; UP000005640; Chromosome 21.
DR Bgee; P48552; -.
DR CleanEx; HS_NRIP1; -.
DR ExpressionAtlas; P48552; baseline and differential.
DR Genevisible; P48552; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0000118; C:histone deacetylase complex; IEA:Ensembl.
DR GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0030331; F:estrogen receptor binding; IPI:UniProtKB.
DR GO; GO:0035259; F:glucocorticoid receptor binding; IPI:UniProtKB.
DR GO; GO:0035257; F:nuclear hormone receptor binding; IPI:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:BHF-UCL.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0001543; P:ovarian follicle rupture; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR InterPro; IPR026649; NRIP1.
DR InterPro; IPR031405; NRIP1_RD1.
DR InterPro; IPR031406; NRIP1_RD2.
DR InterPro; IPR031407; NRIP1_RD3.
DR InterPro; IPR031408; NRIP1_RD4.
DR PANTHER; PTHR15088; PTHR15088; 1.
DR Pfam; PF15687; NRIP1_repr_1; 1.
DR Pfam; PF15688; NRIP1_repr_2; 1.
DR Pfam; PF15689; NRIP1_repr_3; 1.
DR Pfam; PF15690; NRIP1_repr_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Biological rhythms;
KW Complete proteome; Isopeptide bond; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 1158 Nuclear receptor-interacting protein 1.
FT /FTId=PRO_0000057951.
FT REGION 1 415 Interaction with ZNF366.
FT REGION 78 333 Repression domain 1.
FT REGION 410 700 Repression domain 2.
FT REGION 431 472 Required for targeting to small nuclear
FT foci.
FT REGION 735 885 Repression domain 3.
FT REGION 753 1158 Interaction with ZNF366.
FT REGION 1118 1158 Repression domain 4.
FT MOTIF 21 25 LXXLL motif 1.
FT MOTIF 133 137 LXXLL motif 2.
FT MOTIF 185 189 LXXLL motif 3.
FT MOTIF 266 270 LXXLL motif 4.
FT MOTIF 380 384 LXXLL motif 5.
FT MOTIF 440 446 CTBP-binding; principal site.
FT MOTIF 500 504 LXXLL motif 6.
FT MOTIF 565 569 CTBP-binding.
FT MOTIF 599 603 CTBP-binding. {ECO:0000255}.
FT MOTIF 713 717 LXXLL motif 7.
FT MOTIF 819 823 LXXLL motif 8.
FT MOTIF 936 940 LXXLL motif 9.
FT MOTIF 946 950 CTBP-binding.
FT MOTIF 1061 1074 Ligand-dependent nuclear receptor
FT binding. {ECO:0000250}.
FT MOD_RES 104 104 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 111 111 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 158 158 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 207 207 Phosphothreonine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 218 218 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 286 286 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 310 310 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 356 356 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 378 378 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 446 446 N6-acetyllysine.
FT {ECO:0000269|PubMed:11509661}.
FT MOD_RES 481 481 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 487 487 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 518 518 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 528 528 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 542 542 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 606 606 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 671 671 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 807 807 Phosphoserine.
FT {ECO:0000244|PubMed:24275569}.
FT MOD_RES 931 931 N6-acetyllysine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT MOD_RES 1001 1001 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q8CBD1}.
FT CROSSLNK 756 756 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT CROSSLNK 1105 1105 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO2).
FT {ECO:0000244|PubMed:25218447}.
FT VARIANT 37 37 V -> I (in dbSNP:rs9941840).
FT /FTId=VAR_051241.
FT VARIANT 221 221 H -> R (in dbSNP:rs139263261).
FT {ECO:0000269|PubMed:16131398}.
FT /FTId=VAR_023706.
FT VARIANT 315 315 Y -> F (in dbSNP:rs2228507).
FT /FTId=VAR_034142.
FT VARIANT 441 441 I -> V (in dbSNP:rs150468995).
FT {ECO:0000269|PubMed:16131398}.
FT /FTId=VAR_023707.
FT VARIANT 448 448 R -> G (common polymorphism;
FT dbSNP:rs2229742).
FT {ECO:0000269|PubMed:16131398,
FT ECO:0000269|PubMed:7641693}.
FT /FTId=VAR_023708.
FT VARIANT 567 567 N -> S (in dbSNP:rs9975169).
FT /FTId=VAR_051242.
FT VARIANT 803 803 S -> L (in dbSNP:rs61750208).
FT {ECO:0000269|PubMed:16131398}.
FT /FTId=VAR_023709.
FT VARIANT 1079 1079 V -> F. {ECO:0000269|PubMed:16131398}.
FT /FTId=VAR_023710.
FT MUTAGEN 440 443 PIDL->AAAA: Abolishes interaction with
FT CTBP1. {ECO:0000269|PubMed:11509661}.
FT MUTAGEN 440 442 PID->AIA: Abolishes interaction with
FT CTBP1 and attenuates nuclear hormone
FT receptor-dependent transcription
FT repression.
FT MUTAGEN 442 443 DL->AA: Reduces, but does not completely
FT abolish, interaction with CTBP. Reduces
FT transcriptional repression.
FT {ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175}.
FT MUTAGEN 442 443 DL->AS: Disrupts interaction with CTBP1,
FT and CTBP2 to a lesser extent. Disrupts
FT transcriptional repression; when
FT associated with 567-AS-568.
FT {ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175}.
FT MUTAGEN 446 446 K->Q: Disrupts interaction with CTBP1.
FT Decreases lysine acetylation. Disrupts
FT nuclear hormone receptor-dependent
FT transcription repression.
FT {ECO:0000269|PubMed:11509661}.
FT MUTAGEN 446 446 K->R: Does not disrupt nuclear hormone
FT receptor-dependent transcription
FT repression.
FT {ECO:0000269|PubMed:11509661}.
FT MUTAGEN 567 568 NL->AA: Disrupts transcriptional
FT repression. {ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175}.
FT MUTAGEN 567 568 NL->AS: Disrupts interaction with CTBP1
FT and CTBP2. Disrupts transcriptional
FT repression; when associated with 442-AS-
FT 443. {ECO:0000269|PubMed:14736873,
FT ECO:0000269|PubMed:15060175}.
FT MUTAGEN 599 603 SMDLT->PIAAS: Does not further disrupt
FT transcriptional repression; when
FT associated with 442-AA-443 and 567-AA-
FT 568.
FT MUTAGEN 948 949 DL->AA: Abolishes CTBP binding but
FT retains transcriptional repressor
FT activity. {ECO:0000269|PubMed:14736873}.
FT CONFLICT 124 124 P -> R (in Ref. 1; CAA59108).
FT {ECO:0000305}.
FT CONFLICT 721 726 NKGKSE -> TKGRVK (in Ref. 1; CAA59108).
FT {ECO:0000305}.
FT CONFLICT 954 954 S -> I (in Ref. 3; AAH40361).
FT {ECO:0000305}.
FT CONFLICT 1080 1080 T -> A (in Ref. 1; CAA59108).
FT {ECO:0000305}.
FT HELIX 379 385 {ECO:0000244|PDB:2GPO}.
FT HELIX 500 505 {ECO:0000244|PDB:4S15}.
SQ SEQUENCE 1158 AA; 126942 MW; 81FC424968E9A5F6 CRC64;
MTHGEELGSD VHQDSIVLTY LEGLLMHQAA GGSGTAVDKK SAGHNEEDQN FNISGSAFPT
CQSNGPVLNT HTYQGSGMLH LKKARLLQSS EDWNAAKRKR LSDSIMNLNV KKEALLAGMV
DSVPKGKQDS TLLASLLQSF SSRLQTVALS QQIRQSLKEQ GYALSHDSLK VEKDLRCYGV
ASSHLKTLLK KSKVKDQKPD TNLPDVTKNL IRDRFAESPH HVGQSGTKVM SEPLSCAARL
QAVASMVEKR ASPATSPKPS VACSQLALLL SSEAHLQQYS REHALKTQNA NQAASERLAA
MARLQENGQK DVGSYQLPKG MSSHLNGQAR TSSSKLMASK SSATVFQNPM GIIPSSPKNA
GYKNSLERNN IKQAANNSLL LHLLKSQTIP KPMNGHSHSE RGSIFEESST PTTIDEYSDN
NPSFTDDSSG DESSYSNCVP IDLSCKHRTE KSESDQPVSL DNFTQSLLNT WDPKVPDVDI
KEDQDTSKNS KLNSHQKVTL LQLLLGHKNE ENVEKNTSPQ GVHNDVSKFN TQNYARTSVI
ESPSTNRTTP VSTPPLLTSS KAGSPINLSQ HSLVIKWNSP PYVCSTQSEK LTNTASNHSM
DLTKSKDPPG EKPAQNEGAQ NSATFSASKL LQNLAQCGMQ SSMSVEEQRP SKQLLTGNTD
KPIGMIDRLN SPLLSNKTNA VEENKAFSSQ PTGPEPGLSG SEIENLLERR TVLQLLLGNP
NKGKSEKKEK TPLRDESTQE HSERALSEQI LMVKIKSEPC DDLQIPNTNV HLSHDAKSAP
FLGMAPAVQR SAPALPVSED FKSEPVSPQD FSFSKNGLLS RLLRQNQDSY LADDSDRSHR
NNEMALLESK NLCMVPKKRK LYTEPLENPF KKMKNNIVDA ANNHSAPEVL YGSLLNQEEL
KFSRNDLEFK YPAGHGSASE SEHRSWARES KSFNVLKQLL LSENCVRDLS PHRSNSVADS
KKKGHKNNVT NSKPEFSISS LNGLMYSSTQ PSSCMDNRTF SYPGVVKTPV SPTFPEHLGC
AGSRPESGLL NGCSMPSEKG PIKWVITDAE KNEYEKDSPR LTKTNPILYY MLQKGGNSVT
SRETQDKDIW REASSAESVS QVTAKEELLP TAETKASFFN LRSPYNSHMG NNASRPHSAN
GEVYGLLGSV LTIKKESE
//
ID RBBP5_HUMAN Reviewed; 538 AA.
AC Q15291; A8K272; Q7Z6D8; Q8NDZ7;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 11-NOV-2015, entry version 147.
DE RecName: Full=Retinoblastoma-binding protein 5;
DE Short=RBBP-5;
DE AltName: Full=Retinoblastoma-binding protein RBQ-3;
GN Name=RBBP5; Synonyms=RBQ3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION AT THR-252 AND
RP SER-497, AND CHARACTERIZATION.
RC TISSUE=Lung carcinoma, and Testis;
RX PubMed=7558034; DOI=10.1006/geno.1995.1084;
RA Saijo M., Sakai Y., Kishino T., Niikawa N., Matsuura Y., Morino K.,
RA Tamai K., Taya Y.;
RT "Molecular cloning of a human protein that binds to the retinoblastoma
RT protein and chromosomal mapping.";
RL Genomics 27:511-519(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION IN THE MEN1-ASSOCIATED HISTONE METHYLTRANSFERASE
RP COMPLEX.
RX PubMed=14992727; DOI=10.1016/S1097-2765(04)00081-4;
RA Hughes C.M., Rozenblatt-Rosen O., Milne T.A., Copeland T.D.,
RA Levine S.S., Lee J.C., Hayes D.N., Shanmugam K.S., Bhattacharjee A.,
RA Biondi C.A., Kay G.F., Hayward N.K., Hess J.L., Meyerson M.;
RT "Menin associates with a trithorax family histone methyltransferase
RT complex and with the hoxc8 locus.";
RL Mol. Cell 13:587-597(2004).
RN [7]
RP IDENTIFICATION IN THE MLL-LIKE COMPLEX.
RX PubMed=15199122; DOI=10.1128/MCB.24.13.5639-5649.2004;
RA Yokoyama A., Wang Z., Wysocka J., Sanyal M., Aufiero D.J.,
RA Kitabayashi I., Herr W., Cleary M.L.;
RT "Leukemia proto-oncoprotein MLL forms a SET1-like histone
RT methyltransferase complex with menin to regulate Hox gene
RT expression.";
RL Mol. Cell. Biol. 24:5639-5649(2004).
RN [8]
RP IDENTIFICATION IN THE MLL1/MLL COMPLEX.
RX PubMed=15960975; DOI=10.1016/j.cell.2005.04.031;
RA Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J.,
RA Allis C.D., Chait B.T., Hess J.L., Roeder R.G.;
RT "Physical association and coordinate function of the H3 K4
RT methyltransferase MLL1 and the H4 K16 acetyltransferase MOF.";
RL Cell 121:873-885(2005).
RN [9]
RP IDENTIFICATION IN THE SET1 COMPLEX.
RX PubMed=16253997; DOI=10.1074/jbc.M508312200;
RA Lee J.-H., Skalnik D.G.;
RT "CpG-binding protein (CXXC finger protein 1) is a component of the
RT mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue
RT of the yeast Set1/COMPASS complex.";
RL J. Biol. Chem. 280:41725-41731(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE SET1 COMPLEX.
RX PubMed=17355966; DOI=10.1074/jbc.M609809200;
RA Lee J.-H., Tate C.M., You J.-S., Skalnik D.G.;
RT "Identification and characterization of the human Set1B histone H3-
RT Lys4 methyltransferase complex.";
RL J. Biol. Chem. 282:13419-13428(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MLL2/3
RP COMPLEX.
RX PubMed=17500065; DOI=10.1074/jbc.M701574200;
RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T.,
RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.;
RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4
RT methyltransferase complex.";
RL J. Biol. Chem. 282:20395-20406(2007).
RN [13]
RP IDENTIFICATION IN SET1 COMPLEX, AND INTERACTION WITH SETD1A.
RX PubMed=17998332; DOI=10.1128/MCB.01356-07;
RA Lee J.H., Skalnik D.G.;
RT "Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A
RT Histone H3-Lys4 methyltransferase complex to transcription start sites
RT of transcribed human genes.";
RL Mol. Cell. Biol. 28:609-618(2008).
RN [14]
RP IDENTIFICATION IN SET1 COMPLEX, AND INTERACTION WITH WDR82.
RX PubMed=18838538; DOI=10.1128/MCB.00976-08;
RA Wu M., Wang P.F., Lee J.S., Martin-Brown S., Florens L., Washburn M.,
RA Shilatifard A.;
RT "Molecular regulation of H3K4 trimethylation by Wdr82, a component of
RT human Set1/COMPASS.";
RL Mol. Cell. Biol. 28:7337-7344(2008).
RN [15]
RP IDENTIFICATION IN A COMPLEX WITH HCFC1; MKI67; C11ORF30; MATR3; HSPA8;
RP ZNF335; CCAR2; ASCL2; ZNF335 AND WDR5.
RX PubMed=19131338; DOI=10.1074/jbc.M805872200;
RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A.,
RA Samuels H.H.;
RT "Identification and characterization of a novel nuclear protein
RT complex involved in nuclear hormone receptor-mediated gene
RT regulation.";
RL J. Biol. Chem. 284:7542-7552(2009).
RN [16]
RP FUNCTION, CHARACTERIZATION OF THE MLL1/MLL COMPLEX, AND INTERACTION
RP WITH WDR5 AND ASH2L.
RX PubMed=19556245; DOI=10.1074/jbc.M109.014498;
RA Patel A., Dharmarajan V., Vought V.E., Cosgrove M.S.;
RT "On the mechanism of multiple lysine methylation by the human mixed
RT lineage leukemia protein-1 (MLL1) core complex.";
RL J. Biol. Chem. 284:24242-24256(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388 AND SER-389, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-525, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP INTERACTION WITH ZNF335.
RX PubMed=23178126; DOI=10.1016/j.cell.2012.10.043;
RA Yang Y.J., Baltus A.E., Mathew R.S., Murphy E.A., Evrony G.D.,
RA Gonzalez D.M., Wang E.P., Marshall-Walker C.A., Barry B.J., Murn J.,
RA Tatarakis A., Mahajan M.A., Samuels H.H., Shi Y., Golden J.A.,
RA Mahajnah M., Shenhav R., Walsh C.A.;
RT "Microcephaly gene links trithorax and REST/NRSF to control neural
RT stem cell proliferation and differentiation.";
RL Cell 151:1097-1112(2012).
CC -!- FUNCTION: In embryonic stem (ES) cells, plays a crucial role in
CC the differentiation potential, particularly along the neural
CC lineage, regulating gene induction and H3 'Lys-4' methylation at
CC key developmental loci, including that mediated by retinoic acid
CC (By similarity). As part of the MLL1/MLL complex, involved in
CC mono-, di- and trimethylation at 'Lys-4' of histone H3. Histone H3
CC 'Lys-4' methylation represents a specific tag for epigenetic
CC transcriptional activation. {ECO:0000250,
CC ECO:0000269|PubMed:19556245}.
CC -!- SUBUNIT: Component of the SET1 complex, at least composed of the
CC catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5,
CC ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Core component of several
CC methyltransferase-containing complexes including MLL1/MLL, MLL2/3
CC (also named ASCOM complex) and MLL4/WBP7. Each complex is at least
CC composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific
CC histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and
CC KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8,
CC E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX,
CC MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20,
CC PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6,
CC TAF7, TAF9, TEX10 and alpha- and beta-tubulin. Interacts with WDR5
CC and ASH2L; the interaction is direct. Interacts with WDR82 and
CC SETD1A. Part of a complex composed at least of ASCL2,
CC C11orf30/EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A,
CC WDR5 and ZNF335; this complex may have a histone H3-specific
CC methyltransferase activity (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9UBL3:ASH2L; NbExp=18; IntAct=EBI-592823, EBI-540797;
CC Q9HCK8:CHD8; NbExp=2; IntAct=EBI-592823, EBI-1169146;
CC Q13619:CUL4A; NbExp=3; IntAct=EBI-592823, EBI-456106;
CC Q9P0U4:CXXC1; NbExp=5; IntAct=EBI-592823, EBI-949911;
CC Q03164:KMT2A; NbExp=6; IntAct=EBI-592823, EBI-591370;
CC O15047:SETD1A; NbExp=3; IntAct=EBI-592823, EBI-540779;
CC P61964:WDR5; NbExp=6; IntAct=EBI-592823, EBI-540834;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17355966}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15291-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15291-2; Sequence=VSP_035583;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- SIMILARITY: Contains 6 WD repeats. {ECO:0000255|PROSITE-
CC ProRule:PRU00221}.
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DR EMBL; X85134; CAA59446.1; -; mRNA.
DR EMBL; AK290137; BAF82826.1; -; mRNA.
DR EMBL; AL583832; CAI15286.1; -; Genomic_DNA.
DR EMBL; AC093422; CAI15286.1; JOINED; Genomic_DNA.
DR EMBL; AL583832; CAI15287.1; -; Genomic_DNA.
DR EMBL; AC093422; CAI15287.1; JOINED; Genomic_DNA.
DR EMBL; CH471067; EAW91537.1; -; Genomic_DNA.
DR EMBL; CH471067; EAW91538.1; -; Genomic_DNA.
DR EMBL; BC037284; AAH37284.1; -; mRNA.
DR EMBL; BC053856; AAH53856.1; -; mRNA.
DR EMBL; BC075059; AAH75059.1; -; mRNA.
DR EMBL; BC075060; AAH75060.1; -; mRNA.
DR CCDS; CCDS30983.1; -. [Q15291-1]
DR CCDS; CCDS53463.1; -. [Q15291-2]
DR PIR; A57624; A57624.
DR RefSeq; NP_001180201.1; NM_001193272.1. [Q15291-2]
DR RefSeq; NP_001180202.1; NM_001193273.1.
DR RefSeq; NP_005048.2; NM_005057.3. [Q15291-1]
DR UniGene; Hs.519230; -.
DR PDB; 3P4F; X-ray; 2.35 A; B=371-381.
DR PDB; 4X8N; X-ray; 2.10 A; B=347-356.
DR PDB; 4X8P; X-ray; 2.20 A; B=344-355.
DR PDBsum; 3P4F; -.
DR PDBsum; 4X8N; -.
DR PDBsum; 4X8P; -.
DR ProteinModelPortal; Q15291; -.
DR SMR; Q15291; 30-320.
DR BioGrid; 111864; 64.
DR DIP; DIP-29224N; -.
DR IntAct; Q15291; 24.
DR MINT; MINT-3031197; -.
DR STRING; 9606.ENSP00000264515; -.
DR ChEMBL; CHEMBL3137282; -.
DR PhosphoSite; Q15291; -.
DR BioMuta; RBBP5; -.
DR DMDM; 209572664; -.
DR MaxQB; Q15291; -.
DR PaxDb; Q15291; -.
DR PRIDE; Q15291; -.
DR DNASU; 5929; -.
DR Ensembl; ENST00000264515; ENSP00000264515; ENSG00000117222. [Q15291-1]
DR Ensembl; ENST00000367164; ENSP00000356132; ENSG00000117222. [Q15291-2]
DR GeneID; 5929; -.
DR KEGG; hsa:5929; -.
DR UCSC; uc001hbu.2; human. [Q15291-1]
DR UCSC; uc001hbv.2; human. [Q15291-2]
DR CTD; 5929; -.
DR GeneCards; RBBP5; -.
DR H-InvDB; HIX0023636; -.
DR HGNC; HGNC:9888; RBBP5.
DR HPA; HPA049042; -.
DR HPA; HPA058085; -.
DR MIM; 600697; gene.
DR neXtProt; NX_Q15291; -.
DR PharmGKB; PA34252; -.
DR eggNOG; KOG1273; Eukaryota.
DR eggNOG; ENOG410XTA2; LUCA.
DR GeneTree; ENSGT00530000064100; -.
DR HOVERGEN; HBG054324; -.
DR InParanoid; Q15291; -.
DR KO; K14961; -.
DR OMA; EQGVIEW; -.
DR OrthoDB; EOG7S21X6; -.
DR PhylomeDB; Q15291; -.
DR TreeFam; TF313289; -.
DR Reactome; R-HSA-201722; formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-3769402; deactivation of the beta-catenin transactivating complex.
DR SignaLink; Q15291; -.
DR GeneWiki; RBBP5; -.
DR GenomeRNAi; 5929; -.
DR NextBio; 23098; -.
DR PRO; PR:Q15291; -.
DR Proteomes; UP000005640; Chromosome 1.
DR Bgee; Q15291; -.
DR CleanEx; HS_RBBP5; -.
DR ExpressionAtlas; Q15291; baseline and differential.
DR Genevisible; Q15291; HS.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048188; C:Set1C/COMPASS complex; IDA:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0006325; P:chromatin organization; TAS:Reactome.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW.
DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR017986; WD40_repeat_dom.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 5.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator;
KW Complete proteome; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; WD repeat.
FT CHAIN 1 538 Retinoblastoma-binding protein 5.
FT /FTId=PRO_0000051194.
FT REPEAT 22 63 WD 1.
FT REPEAT 64 103 WD 2.
FT REPEAT 148 188 WD 3.
FT REPEAT 196 235 WD 4.
FT REPEAT 249 291 WD 5.
FT REPEAT 293 331 WD 6.
FT MOD_RES 252 252 Phosphothreonine; by CDK1.
FT {ECO:0000269|PubMed:7558034}.
FT MOD_RES 350 350 Phosphoserine.
FT {ECO:0000244|PubMed:17081983}.
FT MOD_RES 388 388 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 389 389 Phosphoserine.
FT {ECO:0000244|PubMed:20068231}.
FT MOD_RES 497 497 Phosphoserine; by CDK1.
FT {ECO:0000269|PubMed:7558034}.
FT MOD_RES 525 525 Phosphoserine.
FT {ECO:0000244|PubMed:21406692}.
FT VAR_SEQ 492 529 Missing (in isoform 2).
FT {ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334}.
FT /FTId=VSP_035583.
FT CONFLICT 206 206 F -> Y (in Ref. 2; BAF82826).
FT {ECO:0000305}.
FT CONFLICT 244 244 K -> E (in Ref. 1; CAA59446).
FT {ECO:0000305}.
FT CONFLICT 351 351 E -> G (in Ref. 1; CAA59446).
FT {ECO:0000305}.
FT TURN 349 352 {ECO:0000244|PDB:4X8N}.
SQ SEQUENCE 538 AA; 59153 MW; 095CCB41613CBED9 CRC64;
MNLELLESFG QNYPEEADGT LDCISMALTC TFNRWGTLLA VGCNDGRIVI WDFLTRGIAK
IISAHIHPVC SLCWSRDGHK LVSASTDNIV SQWDVLSGDC DQRFRFPSPI LKVQYHPRDQ
NKVLVCPMKS APVMLTLSDS KHVVLPVDDD SDLNVVASFD RRGEYIYTGN AKGKILVLKT
DSQDLVASFR VTTGTSNTTA IKSIEFARKG SCFLINTADR IIRVYDGREI LTCGRDGEPE
PMQKLQDLVN RTPWKKCCFS GDGEYIVAGS ARQHALYIWE KSIGNLVKIL HGTRGELLLD
VAWHPVRPII ASISSGVVSI WAQNQVENWS AFAPDFKELD ENVEYEERES EFDIEDEDKS
EPEQTGADAA EDEEVDVTSV DPIAAFCSSD EELEDSKALL YLPIAPEVED PEENPYGPPP
DAVQTSLMDE GASSEKKRQS SADGSQPPKK KPKTTNIELQ GVPNDEVHPL LGVKGDGKSK
KKQAGRPKGS KGKEKDSPFK PKLYKGDRGL PLEGSAKGKV QAELSQPLTA GGAISELL
//
ID SOBP_HUMAN Reviewed; 873 AA.
AC A7XYQ1; B0QZ12; Q5BJD4; Q8N2B2;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 11-NOV-2015, entry version 67.
DE RecName: Full=Sine oculis-binding protein homolog;
DE AltName: Full=Jackson circler protein 1;
GN Name=SOBP {ECO:0000312|EMBL:AAH91526.2};
GN Synonyms=JXC1 {ECO:0000312|EMBL:ABF72848.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000312|EMBL:ABF72848.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-683.
RA Chen Z., Noben-Trauth K.;
RT "Mutations in Jxc1 cause deafness, vestibular deficits and cochlear
RT malformation in the Jackson circler (jc) mutant mouse.";
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3] {ECO:0000312|EMBL:BAC03537.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-224.
RC TISSUE=Amygdala {ECO:0000312|EMBL:BAC03537.1};
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4] {ECO:0000312|EMBL:AAH91526.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-140.
RC TISSUE=Brain {ECO:0000312|EMBL:AAH91526.2};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INVOLVEMENT IN MRAMS.
RX PubMed=21035105; DOI=10.1016/j.ajhg.2010.10.005;
RA Birk E., Har-Zahav A., Manzini C.M., Pasmanik-Chor M., Kornreich L.,
RA Walsh C.A., Noben-Trauth K., Albin A., Simon A.J., Colleaux L.,
RA Morad Y., Rainshtein L., Tischfield D.J., Wang P., Magal N., Maya I.,
RA Shoshani N., Rechavi G., Gothelf D., Maydan G., Shohat M.,
RA Basel-Vanagaite L.;
RT "SOBP is mutated in syndromic and nonsyndromic intellectual disability
RT and is highly expressed in the brain limbic system.";
RL Am. J. Hum. Genet. 87:694-700(2010).
RN [6]
RP IDENTIFICATION OF REPEAT SUMO-INTERACTING MOTIF, AND INTERACTION WITH
RP SUMO1 AND SUMO2.
RX PubMed=23086935; DOI=10.1074/jbc.M112.410985;
RA Sun H., Hunter T.;
RT "PolySUMO-binding proteins identified through a string search.";
RL J. Biol. Chem. 287:42071-42083(2012).
CC -!- FUNCTION: Implicated in development of the cochlea.
CC {ECO:0000250|UniProtKB:Q0P5V2}.
CC -!- SUBUNIT: Interacts (via SIM domains) with SUMO1 and SUMO2.
CC {ECO:0000269|PubMed:23086935}.
CC -!- DISEASE: Mental retardation, anterior maxillary protrusion, and
CC strabismus (MRAMS) [MIM:613671]: A syndrome characterized by
CC severe mental retardation, strabismus and dysmorphic features such
CC as anterior maxillary protrusion with vertical maxillary excess,
CC open bite and prominent crowded teeth. Some patients may lack
CC dysmorphic features and manifest temporal lobe epilepsy and
CC psychosis. Esotropia and amblyopia are present in some
CC individuals. {ECO:0000269|PubMed:21035105}. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SOBP family. {ECO:0000255}.
CC -!- SIMILARITY: Contains 2 FCS-type zinc fingers. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH91526.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=BAC03537.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; DQ507800; ABF72848.1; -; mRNA.
DR EMBL; AL096816; CAQ08124.1; -; Genomic_DNA.
DR EMBL; AL121957; CAQ08124.1; JOINED; Genomic_DNA.
DR EMBL; AL671934; CAQ08124.1; JOINED; Genomic_DNA.
DR EMBL; AL671934; CAQ10205.1; -; Genomic_DNA.
DR EMBL; AL096816; CAQ10205.1; JOINED; Genomic_DNA.
DR EMBL; AL121957; CAQ10205.1; JOINED; Genomic_DNA.
DR EMBL; AL121957; CAQ10380.1; -; Genomic_DNA.
DR EMBL; AL096816; CAQ10380.1; JOINED; Genomic_DNA.
DR EMBL; AL671934; CAQ10380.1; JOINED; Genomic_DNA.
DR EMBL; AK090879; BAC03537.1; ALT_SEQ; mRNA.
DR EMBL; BC091526; AAH91526.2; ALT_SEQ; mRNA.
DR CCDS; CCDS43488.1; -.
DR RefSeq; NP_060483.3; NM_018013.3.
DR UniGene; Hs.445244; -.
DR ProteinModelPortal; A7XYQ1; -.
DR BioGrid; 120399; 3.
DR IntAct; A7XYQ1; 2.
DR MINT; MINT-6778579; -.
DR STRING; 9606.ENSP00000318900; -.
DR PhosphoSite; A7XYQ1; -.
DR BioMuta; SOBP; -.
DR MaxQB; A7XYQ1; -.
DR PaxDb; A7XYQ1; -.
DR PRIDE; A7XYQ1; -.
DR Ensembl; ENST00000317357; ENSP00000318900; ENSG00000112320.
DR GeneID; 55084; -.
DR KEGG; hsa:55084; -.
DR UCSC; uc003prx.3; human.
DR CTD; 55084; -.
DR GeneCards; SOBP; -.
DR H-InvDB; HIX0006109; -.
DR HGNC; HGNC:29256; SOBP.
DR HPA; HPA029242; -.
DR MIM; 613667; gene.
DR MIM; 613671; phenotype.
DR neXtProt; NX_A7XYQ1; -.
DR PharmGKB; PA162404346; -.
DR eggNOG; ENOG410IEAE; Eukaryota.
DR eggNOG; ENOG4111QQS; LUCA.
DR GeneTree; ENSGT00730000111043; -.
DR HOGENOM; HOG000008673; -.
DR HOVERGEN; HBG062766; -.
DR InParanoid; A7XYQ1; -.
DR OMA; EHGRSEV; -.
DR OrthoDB; EOG7F7W8D; -.
DR PhylomeDB; A7XYQ1; -.
DR TreeFam; TF324359; -.
DR ChiTaRS; SOBP; human.
DR GeneWiki; Sobp; -.
DR GenomeRNAi; 55084; -.
DR NextBio; 58645; -.
DR PRO; PR:A7XYQ1; -.
DR Proteomes; UP000005640; Chromosome 6.
DR Bgee; A7XYQ1; -.
DR CleanEx; HS_SOBP; -.
DR ExpressionAtlas; A7XYQ1; baseline and differential.
DR Genevisible; A7XYQ1; HS.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050890; P:cognition; IMP:HGNC.
DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR InterPro; IPR026092; RAI2/SOBP.
DR PANTHER; PTHR23186; PTHR23186; 2.
DR Pfam; PF15279; SOBP; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Mental retardation; Metal-binding; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1 873 Sine oculis-binding protein homolog.
FT /FTId=PRO_0000312232.
FT ZN_FING 142 180 FCS-type 1. {ECO:0000255}.
FT ZN_FING 216 256 FCS-type 2. {ECO:0000255}.
FT MOTIF 620 624 SUMO interaction motif 1 (SIM); mediates
FT the binding to polysumoylated substrates.
FT MOTIF 653 657 SUMO interaction motif 2 (SIM); mediates
FT the binding to polysumoylated substrates.
FT COMPBIAS 346 552 Pro-rich. {ECO:0000255}.
FT COMPBIAS 740 763 Pro-rich. {ECO:0000255}.
FT MOD_RES 629 629 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q0P5V2}.
FT MOD_RES 699 699 Phosphoserine.
FT {ECO:0000250|UniProtKB:Q0P5V2}.
FT VARIANT 683 683 S -> G (in dbSNP:rs9486659).
FT {ECO:0000269|Ref.1}.
FT /FTId=VAR_062215.
FT CONFLICT 623 623 L -> M (in Ref. 1; ABF72848).
FT {ECO:0000305}.
FT CONFLICT 646 646 L -> M (in Ref. 1; ABF72848).
FT {ECO:0000305}.
SQ SEQUENCE 873 AA; 92658 MW; 894DEF718F6E0CB0 CRC64;
MAEMEKEGRP PENKRSRKPA HPVKREINEE MKNFAENTMN ELLGWYGYDK VELKDGEDIE
FRSYPTDGES RQHISVLKEN SLPKPKLPED SVISPYNIST GYSGLATGNG LSDSPAGSKD
HGSVPIIVPL IPPPFIKPPA EDDVSNVQIM CAWCQKVGIK RYSLSMGSEV KSFCSEKCFA
ACRRAYFKRN KARDEDGHAE NFPQQHYAKE TPRLAFKNNC ELLVCDWCKH IRHTKEYLDF
GDGERRLQFC SAKCLNQYKM DIFYKETQAN LPAGLCSTLH PPMENKAEGT GVQLLTPDSW
NIPLTDARRK APSPVATAGQ SQGPGPSAST TVSPSDTANC SVTKIPTPVP KSIPISETPN
IPPVSVQPPA SIGPPLGVPP RSPPMVMTNR GPVPLPIFME QQIMQQIRPP FIRGPPHHAS
NPNSPLSNPM LPGIGPPPGG PRNLGPTSSP MHRPMLSPHI HPPSTPTMPG NPPGLLPPPP
PGAPLPSLPF PPVSMMPNGP MPVPQMMNFG LPSLAPLVPP PTLLVPYPVI VPLPVPIPIP
IPIPHVSDSK PPNGFSSNGE NFIPNAPGDS AAAGGKPSGH SLSPRDSKQG SSKSADSPPG
CSGQALSLAP TPAEHGRSEV VDLTRRAGSP PGPPGAGGQL GFPGVLQGPQ DGVIDLTVGH
RARLHNVIHR ALHAHVKAER EPSAAERRTC GGCRDGHCSP PAAGDPGPGA PAGPEAAAAC
NVIVNGTRGA AAEGAKSAEP PPEQPPPPPP PAPPKKLLSP EEPAVSELES VKENNCASNC
HLDGEAAKKL MGEEALAGGD KSDPNLNNPA DEDHAYALRM LPKTGCVIQP VPKPAEKAAM
APCIISSPML SAGPEDLEPP LKRRCLRIRN QNK
//
ID ZN219_HUMAN Reviewed; 722 AA.
AC Q9P2Y4; D3DS16; Q53Y57; Q8IYC1; Q9BW28;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 2.
DT 11-NOV-2015, entry version 138.
DE RecName: Full=Zinc finger protein 219;
GN Name=ZNF219;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC TISSUE=Testis;
RX PubMed=10819330; DOI=10.1093/dnares/7.2.137;
RA Sakai T., Toyoda A., Hashimoto K., Maeda H.;
RT "Isolation and characterization of a novel zinc finger gene, ZNF219,
RT and mapping to the human chromosome 14q11 region.";
RL DNA Res. 7:137-141(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-260.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-260.
RC TISSUE=Brain, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: May be involved in transcriptional regulation.
CC -!- INTERACTION:
CC P25800:LMO1; NbExp=3; IntAct=EBI-3937106, EBI-8639312;
CC Q5I0X7:TTC32; NbExp=3; IntAct=EBI-3937106, EBI-8636434;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SIMILARITY: Contains 6 C2H2-type zinc fingers.
CC {ECO:0000255|PROSITE-ProRule:PRU00042}.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB015427; BAA90526.1; -; mRNA.
DR EMBL; BT006956; AAP35602.1; -; mRNA.
DR EMBL; CH471078; EAW66404.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66405.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66406.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66407.1; -; Genomic_DNA.
DR EMBL; BC000694; AAH00694.1; -; mRNA.
DR EMBL; BC036105; AAH36105.1; -; mRNA.
DR CCDS; CCDS9568.1; -.
DR RefSeq; NP_001095142.1; NM_001101672.1.
DR RefSeq; NP_001095924.1; NM_001102454.1.
DR RefSeq; NP_057507.2; NM_016423.2.
DR RefSeq; XP_006720226.1; XM_006720163.2.
DR RefSeq; XP_006720227.1; XM_006720164.2.
DR UniGene; Hs.250493; -.
DR ProteinModelPortal; Q9P2Y4; -.
DR SMR; Q9P2Y4; 57-210, 269-331, 393-429, 498-549, 635-675.
DR BioGrid; 119387; 41.
DR IntAct; Q9P2Y4; 10.
DR MINT; MINT-8247371; -.
DR STRING; 9606.ENSP00000354206; -.
DR PhosphoSite; Q9P2Y4; -.
DR BioMuta; ZNF219; -.
DR DMDM; 55977885; -.
DR MaxQB; Q9P2Y4; -.
DR PaxDb; Q9P2Y4; -.
DR PRIDE; Q9P2Y4; -.
DR DNASU; 51222; -.
DR Ensembl; ENST00000360947; ENSP00000354206; ENSG00000165804.
DR Ensembl; ENST00000421093; ENSP00000392401; ENSG00000165804.
DR Ensembl; ENST00000451119; ENSP00000388558; ENSG00000165804.
DR GeneID; 51222; -.
DR KEGG; hsa:51222; -.
DR UCSC; uc001vzr.2; human.
DR CTD; 51222; -.
DR GeneCards; ZNF219; -.
DR HGNC; HGNC:13011; ZNF219.
DR HPA; HPA030761; -.
DR HPA; HPA056168; -.
DR MIM; 605036; gene.
DR neXtProt; NX_Q9P2Y4; -.
DR PharmGKB; PA37590; -.
DR eggNOG; KOG1721; Eukaryota.
DR eggNOG; COG5048; LUCA.
DR GeneTree; ENSGT00530000063100; -.
DR HOGENOM; HOG000140857; -.
DR HOVERGEN; HBG054187; -.
DR InParanoid; Q9P2Y4; -.
DR OMA; DASPPYA; -.
DR OrthoDB; EOG7D59N5; -.
DR PhylomeDB; Q9P2Y4; -.
DR TreeFam; TF332241; -.
DR ChiTaRS; ZNF219; human.
DR GeneWiki; ZNF219; -.
DR GenomeRNAi; 51222; -.
DR NextBio; 54298; -.
DR PRO; PR:Q9P2Y4; -.
DR Proteomes; UP000005640; Chromosome 14.
DR Bgee; Q9P2Y4; -.
DR CleanEx; HS_ZNF219; -.
DR ExpressionAtlas; Q9P2Y4; baseline and differential.
DR Genevisible; Q9P2Y4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0004969; F:histamine receptor activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB.
DR GO; GO:0007275; P:multicellular organismal development; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0001505; P:regulation of neurotransmitter levels; IEA:InterPro.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR Gene3D; 3.30.160.60; -; 6.
DR InterPro; IPR003980; Histamine_H3_rcpt.
DR InterPro; IPR007087; Znf_C2H2.
DR InterPro; IPR015880; Znf_C2H2-like.
DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd.
DR PRINTS; PR01471; HISTAMINEH3R.
DR SMART; SM00355; ZnF_C2H2; 9.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6.
PE 1: Evidence at protein level;
KW Complete proteome; DNA-binding; Metal-binding; Nucleus; Polymorphism;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1 722 Zinc finger protein 219.
FT /FTId=PRO_0000047461.
FT ZN_FING 57 79 C2H2-type 1. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 85 107 C2H2-type 2. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 163 186 C2H2-type 3. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 274 296 C2H2-type 4. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 302 324 C2H2-type 5. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT ZN_FING 498 520 C2H2-type 6. {ECO:0000255|PROSITE-
FT ProRule:PRU00042}.
FT VARIANT 260 260 P -> T (in dbSNP:rs17853549).
FT {ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.2}.
FT /FTId=VAR_067624.
FT CONFLICT 232 233 Missing (in Ref. 4; AAH00694).
FT {ECO:0000305}.
FT CONFLICT 436 436 E -> Q (in Ref. 1; BAA90526).
FT {ECO:0000305}.
SQ SEQUENCE 722 AA; 76877 MW; AB2B6B37904FC14B CRC64;
MEGSRPRAPS GHLAPSPPAF DGELDLQRYS NGPAVSAGSL GMGAVSWSES RAGERRFPCP
VCGKRFRFNS ILALHLRAHP GAQAFQCPHC GHRAAQRALL RSHLRTHQPE RPRSPAARLL
LELEERALLR EARLGRARSS GGMQATPATE GLARPQAPSS SAFRCPYCKG KFRTSAERER
HLHILHRPWK CGLCSFGSSQ EEELLHHSLT AHGAPERPLA ATSAAPPPQP QPQPPPQPEP
RSVPQPEPEP EPEREATPTP APAAPEEPPA PPEFRCQVCG QSFTQSWFLK GHMRKHKASF
DHACPVCGRC FKEPWFLKNH MKVHASKLGP LRAPGPASGP ARAPQPPDLG LLAYEPLGPA
LLLAPAPTPA ERREPPSLLG YLSLRAGEGR PNGEGAEPGP GRSFGGFRPL SSALPARARR
HRAEEPEEEE EVVEAEEETW ARGRSLGSLA SLHPRPGEGP GHSASAAGAQ ARSTATQEEN
GLLVGGTRPE GGRGATGKDC PFCGKSFRSA HHLKVHLRVH TGERPYKCPH CDYAGTQSGS
LKYHLQRHHR EQRSGAGPGP PPEPPPPSQR GSAPQSGAKP SPQPATWVEG ASSPRPPSSG
AGPGSRRKPA SPGRTLRNGR GGEAEPLDLS LRAGPGGEAG PGGALHRCLF CPFATGAPEL
MALHLQVHHS RRARGRRPPQ ADASPPYARV PSGETPPSPS QEGEEGSGLS RPGEAGLGGQ
ER
//
Click here and save the page to download this output.
#~~# |
#~+~~+~# |
#~~# |
#LOG |
00:00:00 |
Activity Log for SLiMSuite V1.5.2: Wed Dec 9 00:29:07 2015 |
#DIR |
00:00:00 |
Run from directory: /srv/slimsuite/logs/prod |
#ARG |
00:00:00 |
Commandline arguments: run ip=129.94.133.155 slimfinder&uniprotid=CTBP1&dismask=T&runid=CtBP1-DisMask&jobid=15120900002 |
#VIO |
00:00:00 |
Verbosity: -1; Interactivity: -1. |
#PROG |
00:00:00 |
SLiMFinder V5.2.3: Short Linear Motif Finder |
#CMD |
00:00:00 |
Full SLiMFinder CmdList: proglog=F iucut=0.2 usegopher=T protscores=T megablam=F orthdb=qfo_ref.2015-04.Eukaryota.fas sourcedate=2015-04-15 walltime=0 maxgapx=3 rest=format uniprotid=CTBP1.hint.acc dismask=T runid=CtBP1-DisMask jobid=15120900002 resfile=slimfinder.csv savespace=0 targz=F megaslim=seqin basefile=slimfinder |
#DB |
00:00:00 |
/srv/slimsuite/data/orthdb/qfo_ref.2015-04/qfo_ref.2015-04.Eukaryota.fas already formatted. (Force = False). |
#DB |
00:00:00 |
/srv/slimsuite/data/orthdb/qfo_ref.2015-04/qfo_ref.2015-04.Eukaryota.fas already formatted. (Force = False). |
#ALPH |
00:00:00 |
Alphabet: A C D E F G H I K L M N P Q R S T V W Y |
#WARN |
00:00:00 |
NOTE: cloudfix=F. Be wary of ambiguity over-predictions. |
#URL |
00:00:06 |
Extracting 20 AccNum from http://www.uniprot.org/uniprot/: 20 read & extracted; 0 failed; 0 duplicates. |
#DAT |
00:00:06 |
Extracting entries from slimfinder.dat: 20 read, 20 extracted. |
#SEQ |
00:00:06 |
20 sequences loaded from /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.dat (Format: uniprot). |
#FAS |
00:00:06 |
20 Sequences output to /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.fas. |
#UPC |
00:00:06 |
No UPC file found. |
#FAS |
00:00:06 |
20 Sequences output to /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.slimdb. |
#DICT |
00:00:06 |
Made "short" seqName dictionary: 20 seq; 20 keys. |
#DB |
00:00:06 |
/share/apps/blast+/2.2.29/bin/makeblastdb -in "/srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.slimdb" -out "/srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.slimdb" -title "/srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.slimdb" -parse_seqids -dbtype prot |
#SYS |
00:00:06 |
/share/apps/blast+/2.2.29/bin/blastp -query /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.slimdb -db /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.slimdb -out /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.self.blast -seg yes -comp_based_stats F -soft_masking true -evalue 1.000000e-04 -num_descriptions 20 -num_alignments 20 |
#INDEX |
00:00:07 |
Indexed "Search" on "Query": 20 unique; 0 missing entries |
#CLUST |
00:00:07 |
16 clusters generated from 20 keys (maxdis=1.00) |
#DICT |
00:00:07 |
Made "short" seqName dictionary: 20 seq; 20 keys. |
#MST |
00:00:07 |
MST for 20 sequences = 19.049. |
#UP |
00:00:07 |
slimfinder: 20 Seq; 16 UPC; 19.049 MST; blaste=1.00e-04, blastcf=F, blastf=T |
#MAT |
00:00:07 |
slimfinder GABLAM Distance matrix out to /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.dis.tdt (text format). |
#MIN |
00:00:07 |
AmbOcc 0.05 & 16 UP => AmbOcc 2 UPC. |
#MIN |
00:00:07 |
MinOcc 0.05 & 16 UP => MinOcc 3 UPC. |
#DIS |
00:00:07 |
Disorder score file: /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.iupred.txt |
#MASK |
00:00:07 |
ATX1L_HUMAN__P0C7T5 masked 21 ordered regions. (107 X added.) |
#MASK |
00:00:07 |
BRCA1_HUMAN__P38398 masked 20 ordered regions. (268 X added.) |
#MASK |
00:00:07 |
CBX4_HUMAN__O00257 masked 3 ordered regions. (54 X added.) |
#MASK |
00:00:07 |
CHD3_HUMAN__Q12873 masked 58 ordered regions. (747 X added.) |
#MASK |
00:00:07 |
COM1_HUMAN__Q99708 masked 14 ordered regions. (46 X added.) |
#MASK |
00:00:07 |
CTBP1_HUMAN__Q13363 masked 13 ordered regions. (221 X added.) |
#MASK |
00:00:07 |
CTNA1_HUMAN__P35221 masked 33 ordered regions. (329 X added.) |
#MASK |
00:00:07 |
HDAC2_HUMAN__Q92769 masked 18 ordered regions. (240 X added.) |
#MASK |
00:00:07 |
HIC1_HUMAN__Q14526 masked 22 ordered regions. (221 X added.) |
#MASK |
00:00:07 |
IKZF1_HUMAN__Q13422 masked 8 ordered regions. (110 X added.) |
#MASK |
00:00:07 |
ITF2_HUMAN__P15884 masked 3 ordered regions. (30 X added.) |
#MASK |
00:00:07 |
KAT2B_HUMAN__Q92831 masked 24 ordered regions. (408 X added.) |
#MASK |
00:00:07 |
LCORL_HUMAN__Q8N3X6 masked 22 ordered regions. (117 X added.) |
#MASK |
00:00:07 |
LCOR_HUMAN__Q96JN0 masked 7 ordered regions. (17 X added.) |
#MASK |
00:00:07 |
MDS1_HUMAN__Q13465 masked 3 ordered regions. (35 X added.) |
#MASK |
00:00:07 |
NOL4L_HUMAN__Q96MY1 masked 2 ordered regions. (27 X added.) |
#MASK |
00:00:07 |
NRIP1_HUMAN__P48552 masked 10 ordered regions. (26 X added.) |
#MASK |
00:00:07 |
RBBP5_HUMAN__Q15291 masked 14 ordered regions. (234 X added.) |
#MASK |
00:00:07 |
SOBP_HUMAN__A7XYQ1 masked 7 ordered regions. (143 X added.) |
#MASK |
00:00:07 |
ZN219_HUMAN__Q9P2Y4 masked 15 ordered regions. (96 X added.) |
#IUPRED |
00:00:07 |
iupred disorder score lists output to /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.iupred.txt for 7 sequences. |
#FTMASK |
00:00:07 |
FTMask: None |
#MASK |
00:00:07 |
Masked ATX1L_HUMAN__P0C7T5 "low complexity" regions. (9 X added.) |
#MASK |
00:00:07 |
Masked BRCA1_HUMAN__P38398 "low complexity" regions. (6 X added.) |
#MASK |
00:00:07 |
Masked CBX4_HUMAN__O00257 "low complexity" regions. (21 X added.) |
#MASK |
00:00:07 |
Masked CHD3_HUMAN__Q12873 "low complexity" regions. (36 X added.) |
#MASK |
00:00:07 |
Masked COM1_HUMAN__Q99708 "low complexity" regions. (3 X added.) |
#MASK |
00:00:07 |
Masked CTNA1_HUMAN__P35221 "low complexity" regions. (3 X added.) |
#MASK |
00:00:07 |
Masked HIC1_HUMAN__Q14526 "low complexity" regions. (33 X added.) |
#MASK |
00:00:07 |
Masked ITF2_HUMAN__P15884 "low complexity" regions. (10 X added.) |
#MASK |
00:00:07 |
Masked KAT2B_HUMAN__Q92831 "low complexity" regions. (19 X added.) |
#MASK |
00:00:07 |
Masked LCORL_HUMAN__Q8N3X6 "low complexity" regions. (9 X added.) |
#MASK |
00:00:07 |
Masked NOL4L_HUMAN__Q96MY1 "low complexity" regions. (14 X added.) |
#MASK |
00:00:07 |
Masked NRIP1_HUMAN__P48552 "low complexity" regions. (6 X added.) |
#MASK |
00:00:07 |
Masked RBBP5_HUMAN__Q15291 "low complexity" regions. (3 X added.) |
#MASK |
00:00:07 |
Masked SOBP_HUMAN__A7XYQ1 "low complexity" regions. (23 X added.) |
#MASK |
00:00:07 |
Masked ZN219_HUMAN__Q9P2Y4 "low complexity" regions. (35 X added.) |
#MASK |
00:00:07 |
MetMask: 20 N-terminal Ms masked |
#MASK |
00:00:07 |
Masked HDAC2_HUMAN__Q92769 position-specific AAs. (1 X added.) |
#MASK |
00:00:07 |
Masked SOBP_HUMAN__A7XYQ1 position-specific AAs. (1 X added.) |
#MASK |
00:00:07 |
slimfinder: Masking of input sequences complete. |
#SPACE |
00:00:07 |
Motif Space, 2 positions: 1,200 motifs |
#SPACE |
00:00:07 |
Motif Space, 3 positions: 72,000 motifs |
#SPACE |
00:00:07 |
Motif Space, 4 positions: 4,320,000 motifs |
#SPACE |
00:00:07 |
Motif Space, 5 positions: 259,200,000 motifs |
#DIM |
00:00:07 |
Read dimers from 20 seq: 1,241 dimers |
#DIM |
00:00:07 |
Reducing dimers: 1,180 >= 2 of 16 UPC |
#SLIM |
00:00:07 |
Selecting 2aa SLiMs: 1,180 >= 2 of 16 UPC |
#AMB |
00:00:07 |
Adding Wildcard ambiguity: 100.0% (0 amb motifs) |
#AMB |
00:00:07 |
Adding Degeneracy ambiguity: 100.0% (0 amb motifs) |
#SLIM |
00:00:46 |
Extending 3aa SLiMs >= 2 of 16 UPC: 21,137 SLiMs |
#AMB |
00:00:56 |
Adding Wildcard ambiguity: 100.0% (6,230 amb motifs) |
#AMB |
00:01:35 |
Adding Degeneracy ambiguity: 100.0% (11,317 amb motifs) |
#SLIM |
00:03:38 |
Extending 4aa SLiMs >= 2 of 16 UPC: 20,241 SLiMs |
#AMB |
00:03:45 |
Adding Wildcard ambiguity: 100.0% (5,200 amb motifs) |
#AMB |
00:04:00 |
Adding Degeneracy ambiguity: 100.0% (7,266 amb motifs) |
#SLIM |
00:05:30 |
Extending 5aa SLiMs >= 2 of 16 UPC: 4,889 SLiMs |
#AMB |
00:05:32 |
Adding Wildcard ambiguity: 100.0% (205 amb motifs) |
#AMB |
00:05:38 |
Adding Degeneracy ambiguity: 100.0% (108 amb motifs) |
#SLIM |
00:05:38 |
77,773 SLiMs >= 2 of 16 UPC |
#SAVE |
00:05:46 |
SLiMFinder Intermediate saved as /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.l5w2o2a3.FreqDisComp-5-8.pickle (Python pickle). |
#GZIP |
00:05:47 |
/srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.l5w2o2a3.FreqDisComp-5-8.pickle zipped. |
#SLIM |
00:05:48 |
Filtering 77,773 SLiMs: 40,608 retained. |
#PROB |
00:06:08 |
Calculating [Sig] SLiM Probabilities (Sig<=0.10) complete: 0 ranked SLiMs. |
#COMB |
00:06:08 |
Combined Occurrence Attributes complete. |
#CLOUD |
00:06:08 |
Making "Motif Clouds" for 0 Sig Motifs: 0 Clouds |
#FAS |
00:06:08 |
20 Sequences output to /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.l5w2o2a3.CtBP1-DisMask.masked.fas. |
#EXTRA |
00:06:08 |
No SLiMs for additional outputs |
#RES |
00:06:08 |
SLiMFinder results output to /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.csv and /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.occ.csv. |
#RES |
00:06:08 |
Additional dataset results output to /srv/slimsuite/scratch/prod/slimfinder/15120900002/slimfinder.* |
#END |
00:06:08 |
No SLiMs for output. Try relaxing probability threshold (probcut) and setting number of SLiMs to return (topranks) > 0. |
#WARN |
00:06:08 |
1 warning messages: check log for details. |
#LOG |
00:06:08 |
SLiMFinder V5.2.3 End: Wed Dec 9 00:35:16 2015 |
#JOBID |
00:06:08 |
15120900002 |
#REST |
00:06:08 |
URL for future retrieval: http://rest.slimsuite.unsw.edu.au/retrieve&jobid=15120900002&rest=format&password=None |
Click here and save the page to download this output.
#WARN 00:00:00 NOTE: cloudfix=F. Be wary of ambiguity over-predictions.
© 2015 RJ Edwards. Contact: richard.edwards@unsw.edu.au.
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