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}; 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; 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 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"; 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; 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 E1A_ADE02 Reviewed; 289 AA. AC P03254; P24934; Q67788; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 11-NOV-2015, entry version 96. DE RecName: Full=Early E1A protein {ECO:0000305}; DE AltName: Full=Early E1A 32 kDa protein; OS Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2). OC Viruses; dsDNA viruses, no RNA stage; Adenoviridae; Mastadenovirus. OX NCBI_TaxID=10515; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS EARLY E1A 32 KDA PROTEIN RP AND EARLY E1A 26 KDA PROTEIN). RX PubMed=551290; DOI=10.1038/281694a0; RA Perricaudet M., Akusjaervi G., Virtanen A., Pettersson U.; RT "Structure of two spliced mRNAs from the transforming region of human RT subgroup C adenoviruses."; RL Nature 281:694-696(1979). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS EARLY E1A 32 KDA PROTEIN; RP EARLY E1A 26 KDA PROTEIN AND EARLY E1A 6 KDA PROTEIN). RX PubMed=7142161; RA Gingeras T.R., Sciaky D., Gelinas R.E., Bing-Dong J., Yen C.E., RA Kelly M.M., Bullock P.A., Parsons B.L., O'Neill K.E., Roberts R.J.; RT "Nucleotide sequences from the adenovirus-2 genome."; RL J. Biol. Chem. 257:13475-13491(1982). RN [3] RP INTERACTION WITH HOST ATF7, AND MUTAGENESIS OF CYS-157; THR-178 AND RP SER-185. RX PubMed=8417352; RA Chatton B., Bocco J.L., Gaire M., Hauss C., Reimund B., Goetz J., RA Kedinger C.; RT "Transcriptional activation by the adenovirus larger E1a product is RT mediated by members of the cellular transcription factor ATF family RT which can directly associate with E1a."; RL Mol. Cell. Biol. 13:561-570(1993). CC -!- FUNCTION: Plays a role in viral genome replication by driving CC entry of quiescent cells into the cell cycle. Stimulation of CC progression from G1 to S phase allows the virus to efficiently use CC the cellular DNA replicating machinery to achieve viral genome CC replication. E1A protein has both transforming and trans- CC activating activities. Induces the disassembly of the E2F1 CC transcription factor from RB1 by direct competition for the same CC binding site on RB1, with subsequent transcriptional activation of CC E2F1-regulated S-phase genes and of the E2 region of the CC adenoviral genome. Release of E2F1 leads to the ARF-mediated CC inhibition of MDM2 and causes TP53/p53 to accumulate because it is CC not targeted for degradation by MDM2-mediated ubiquitination CC anymore. This increase in TP53, in turn, would arrest the cell CC proliferation and direct its death but this effect is counteracted CC by the viral protein E1B-55K. Inactivation of the ability of RB1 CC to arrest the cell cycle is critical for cellular transformation, CC uncontrolled cellular growth and proliferation induced by viral CC infection. Interaction with RBX1 and CUL1 inhibits ubiquitination CC of the proteins targeted by SCF(FBXW7) ubiquitin ligase complex, CC and may be linked to unregulated host cell proliferation. The CC tumorigenesis-restraining activity of E1A may be related to the CC disruption of the host CtBP-CtIP complex through the CtBP binding CC motif. Interacts with host TBP protein; this interaction probably CC disrupts the TBP-TATA complex. {ECO:0000250|UniProtKB:P03255}. CC -!- SUBUNIT: Interacts with host UBE2I; this interaction interferes CC with polySUMOylation. Interacts with host RB1; this interaction CC induces the aberrant dissociation of RB1-E2F1 complex thereby CC disrupting the activity of RB1 and activating E2F1-regulated CC genes. Interacts with host ATF7; the interaction enhances ATF7- CC mediated viral transactivation activity which requires the zinc CC binding domains of both proteins. Isoform early E1A 32 kDa protein CC and isoform early E1A 26 kDa protein interact (via N-terminus) CC with CUL1 and E3 ubiquitin ligase RBX1; these interactions inhibit CC RBX1-CUL1-dependent elongation reaction of ubiquitin chains and CC attenuate ubiquitination of SCF(FBXW7) target proteins. Interacts CC (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc CC finger); this interaction inhibits E1A mediated transactivation. CC Interacts with host EP300; this interaction stimulates the CC acetylation of RB1 by recruiting EP300 and RB1 into a multimeric- CC protein complex. Interacts with host CTBP1 and CTBP2; this CC interaction seems to potentiate viral replication. Interacts with CC host DCAF7. Interacts with host DYRK1A. Interacts with host KPNA4; CC this interaction allows E1A import into the host nucleus. CC Interacts with host EP400; this interaction stabilizes MYC. CC {ECO:0000250|UniProtKB:P03255}. CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:P03255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Isoforms are derived from the E1 region of the genome.; CC Name=early E1A 32 kDa protein; Synonyms=289R, L-E1A; CC IsoId=P03254-1; Sequence=Displayed; CC Name=early E1A 26 kDa protein; Synonyms=243R, S-E1A; CC IsoId=P03254-2; Sequence=VSP_000197; CC Name=early E1A 6 kDa protein; CC IsoId=P03254-3; Sequence=VSP_028916, VSP_028917; CC -!- SIMILARITY: Belongs to the adenoviridae E1A protein family. CC {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; J01917; AAA92197.1; -; Genomic_DNA. DR EMBL; J01917; AAA92198.1; -; Genomic_DNA. DR EMBL; J01917; AAA92199.1; -; Genomic_DNA. DR PIR; A03824; Q2AD2. DR RefSeq; AP_000161.1; AC_000007.1. DR DIP; DIP-570N; -. DR IntAct; P03254; 1. DR MINT; MINT-198575; -. DR Proteomes; UP000008167; Genome. DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0039695; P:DNA-templated viral transcription; IDA:UniProtKB. DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW. DR GO; GO:0039649; P:modulation by virus of host ubiquitin-protein ligase activity; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0039657; P:suppression by virus of host gene expression; IEA:UniProtKB-KW. DR GO; GO:0039563; P:suppression by virus of host STAT1 activity; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR InterPro; IPR014410; Aden_E1A. DR Pfam; PF02703; Adeno_E1A; 1. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Complete proteome; Early protein; KW Eukaryotic host gene expression shutoff by virus; KW Eukaryotic host transcription shutoff by virus; KW G1/S host cell cycle checkpoint dysregulation by virus; KW Host gene expression shutoff by virus; Host nucleus; KW Host-virus interaction; KW Inhibition of eukaryotic host transcription initiation by virus; KW Inhibition of host innate immune response by virus; KW Inhibition of host interferon signaling pathway by virus; KW Inhibition of host STAT1 by virus; Metal-binding; KW Modulation of host cell cycle by virus; KW Modulation of host E3 ubiquitin ligases by virus; KW Modulation of host ubiquitin pathway by virus; Oncogene; KW Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Viral immunoevasion; Zinc; Zinc-finger. FT CHAIN 1 289 Early E1A protein. FT /FTId=PRO_0000221692. FT ZN_FING 154 174 {ECO:0000250|UniProtKB:P03255}. FT REGION 41 49 Interaction with RB1 in competition with FT E2F1. {ECO:0000250}. FT REGION 76 140 Interaction with UBE2I. {ECO:0000250}. FT MOTIF 113 117 PXLXP motif, interaction with host FT ZMYND11. {ECO:0000250}. FT MOTIF 122 126 LXCXE motif, interaction with host RB1. FT {ECO:0000255}. FT MOTIF 258 289 Bipartite nuclear localization signal. FT {ECO:0000250|UniProtKB:P03255, FT ECO:0000255}. FT MOTIF 279 283 PXDLS motif, CTBP-binding. FT {ECO:0000250|UniProtKB:P03255}. FT MOD_RES 89 89 Phosphoserine; by host. {ECO:0000250}. FT MOD_RES 219 219 Phosphoserine; by host. {ECO:0000250}. FT MOD_RES 231 231 Phosphoserine; by host. {ECO:0000250}. FT VAR_SEQ 29 55 ADNLPPPSHFEPPTLHELYDLDVTAPE -> CLNLSLSPSQ FT NRSLQDLPGVLNWCLLS (in isoform early E1A 6 FT kDa protein). {ECO:0000305}. FT /FTId=VSP_028916. FT VAR_SEQ 56 289 Missing (in isoform early E1A 6 kDa FT protein). {ECO:0000305}. FT /FTId=VSP_028917. FT VAR_SEQ 140 185 Missing (in isoform early E1A 26 kDa FT protein). {ECO:0000305}. FT /FTId=VSP_000197. FT MUTAGEN 157 157 C->S: Abolishes ATF7-mediated FT transcriptional activation. FT {ECO:0000269|PubMed:8417352}. FT MUTAGEN 178 178 T->P: No effect on ATF7-mediated FT transcriptional activation. FT {ECO:0000269|PubMed:8417352}. FT MUTAGEN 185 185 S->R: Abolishes ATF7-mediated FT transcriptional activation. FT {ECO:0000269|PubMed:8417352}. FT CONFLICT 68 68 D -> E (in Ref. 2; AAA92197/AAA92199). FT {ECO:0000305}. FT CONFLICT 81 81 L -> F (in Ref. 2; AAA92197/AAA92199). FT {ECO:0000305}. SQ SEQUENCE 289 AA; 31851 MW; 4264747DAD74FFC5 CRC64; MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD VTAPEDPNEE AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE QPEQRALGPV SMPNLVPEVI DLTCHEAGFP PSDDEDEEGE EFVLDYVEHP GHGCRSCHYH RRNTGDPDIM CSLCYMRTCG MFVYSPVSEP EPEPEPEPEP ARPTRRPKLV PAILRRPTSP VSRECNSSTD SCDSGPSNTP PEIHPVVPLC PIKPVAVRVG GRRQAVECIE DLLNESGQPL DLSCKRPRP // ID ELK3_HUMAN Reviewed; 407 AA. AC P41970; B2R6S6; Q6FG57; Q6GU29; Q9UD17; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 11-NOV-2015, entry version 142. DE RecName: Full=ETS domain-containing protein Elk-3; DE AltName: Full=ETS-related protein ERP; DE AltName: Full=ETS-related protein NET; DE AltName: Full=Serum response factor accessory protein 2; DE Short=SAP-2; DE Short=SRF accessory protein 2; GN Name=ELK3; Synonyms=NET, SAP2; 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]. RX PubMed=7958835; DOI=10.1101/gad.8.13.1502; RA Giovane A., Pintzas A., Maira S.-M., Sobieszczuk P., Wasylyk B.; RT "Net, a new ets transcription factor that is activated by Ras."; RL Genes Dev. 8:1502-1513(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=7540136; RA Price M.A., Rogers A.E., Treisman R.; RT "Comparative analysis of the ternary complex factors Elk-1, SAP-1a and RT SAP-2 (ERP/NET)."; RL EMBO J. 14:2589-2601(1995). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 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]. 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-115, 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). CC -!- FUNCTION: May be a negative regulator of transcription, but can CC activate transcription when coexpressed with Ras, Src or Mos. CC Forms a ternary complex with the serum response factor and the ETS CC and SRF motifs of the Fos serum response element. CC -!- SUBUNIT: Interacts with CTBP1. CC -!- INTERACTION: CC P16333:NCK1; NbExp=3; IntAct=EBI-1758534, EBI-389883; CC P27986:PIK3R1; NbExp=2; IntAct=EBI-1758534, EBI-79464; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 ETS DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00237}. 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; Z36715; CAA85309.1; -; mRNA. DR EMBL; CR542251; CAG47047.1; -; mRNA. DR EMBL; AK312694; BAG35573.1; -; mRNA. DR EMBL; CH471054; EAW97561.1; -; Genomic_DNA. DR EMBL; BC017371; AAH17371.1; -; mRNA. DR CCDS; CCDS9060.1; -. DR PIR; I38062; I38062. DR RefSeq; NP_005221.2; NM_005230.3. DR RefSeq; XP_006719338.1; XM_006719275.2. DR UniGene; Hs.46523; -. DR UniGene; Hs.718709; -. DR ProteinModelPortal; P41970; -. DR SMR; P41970; 2-151. DR BioGrid; 108319; 3. DR IntAct; P41970; 4. DR MINT; MINT-7242082; -. DR STRING; 9606.ENSP00000228741; -. DR PhosphoSite; P41970; -. DR BioMuta; ELK3; -. DR DMDM; 116241349; -. DR MaxQB; P41970; -. DR PaxDb; P41970; -. DR PRIDE; P41970; -. DR DNASU; 2004; -. DR Ensembl; ENST00000228741; ENSP00000228741; ENSG00000111145. DR GeneID; 2004; -. DR UCSC; uc001teo.1; human. DR CTD; 2004; -. DR GeneCards; ELK3; -. DR HGNC; HGNC:3325; ELK3. DR HPA; HPA001600; -. DR MIM; 600247; gene. DR neXtProt; NX_P41970; -. DR PharmGKB; PA27752; -. DR eggNOG; KOG3806; Eukaryota. DR eggNOG; ENOG410Z0ZF; LUCA. DR GeneTree; ENSGT00760000118996; -. DR HOGENOM; HOG000237332; -. DR HOVERGEN; HBG004344; -. DR InParanoid; P41970; -. DR OMA; EISAPPM; -. DR OrthoDB; EOG7NPFTD; -. DR PhylomeDB; P41970; -. DR TreeFam; TF317732; -. DR SignaLink; P41970; -. DR GeneWiki; ELK3; -. DR GenomeRNAi; 2004; -. DR NextBio; 8109; -. DR PRO; PR:P41970; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; P41970; -. DR CleanEx; HS_ELK3; -. DR ExpressionAtlas; P41970; baseline and differential. DR Genevisible; P41970; HS. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IC:HGNC. DR GO; GO:0032422; F:purine-rich negative regulatory element binding; IDA:HGNC. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0003714; F:transcription corepressor activity; IDA:HGNC. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; NAS:ProtInc. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:HGNC. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:GOC. DR GO; GO:0042060; P:wound healing; IEA:Ensembl. DR Gene3D; 1.10.10.10; -; 1. DR InterPro; IPR000418; Ets_dom. DR InterPro; IPR011991; WHTH_DNA-bd_dom. DR Pfam; PF00178; Ets; 1. DR PRINTS; PR00454; ETSDOMAIN. DR SMART; SM00413; ETS; 1. DR PROSITE; PS00345; ETS_DOMAIN_1; 1. DR PROSITE; PS00346; ETS_DOMAIN_2; 1. DR PROSITE; PS50061; ETS_DOMAIN_3; 1. PE 1: Evidence at protein level; KW Activator; Complete proteome; DNA-binding; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1 407 ETS domain-containing protein Elk-3. FT /FTId=PRO_0000204097. FT DNA_BIND 5 85 ETS. {ECO:0000255|PROSITE- FT ProRule:PRU00237}. FT MOTIF 273 277 CTBP-binding motif. FT COMPBIAS 207 212 Poly-Ala. FT MOD_RES 115 115 Phosphoserine. FT {ECO:0000244|PubMed:18691976}. FT VARIANT 169 169 P -> L (in dbSNP:rs35332676). FT /FTId=VAR_048946. FT CONFLICT 114 114 A -> V (in Ref. 1; CAA85309). FT {ECO:0000305}. FT CONFLICT 117 117 E -> G (in Ref. 3; CAG47047). FT {ECO:0000305}. FT CONFLICT 128 128 A -> V (in Ref. 1; CAA85309). FT {ECO:0000305}. FT CONFLICT 152 152 Q -> E (in Ref. 1; CAA85309). FT {ECO:0000305}. FT CONFLICT 163 163 T -> R (in Ref. 1; CAA85309). FT {ECO:0000305}. FT CONFLICT 249 249 N -> K (in Ref. 1; CAA85309). FT {ECO:0000305}. SQ SEQUENCE 407 AA; 44240 MW; DD4515270ECED1E3 CRC64; MESAITLWQF LLQLLLDQKH EHLICWTSND GEFKLLKAEE VAKLWGLRKN KTNMNYDKLS RALRYYYDKN IIKKVIGQKF VYKFVSFPEI LKMDPHAVEI SRESLLLQDS DCKASPEGRE AHKHGLAALR STSRNEYIHS GLYSSFTINS LQNPPDAFKA IKTEKLEEPP EDSPPVEEVR TVIRFVTNKT DKHVTRPVVS LPSTSEAAAA SAFLASSVSA KISSLMLPNA ASISSASPFS SRSPSLSPNS PLPSEHRSLF LEAACHDSDS LEPLNLSSGS KTKSPSLPPK AKKPKGLEIS APPLVLSGTD IGSIALNSPA LPSGSLTPAF FTAQTPNGLL LTPSPLLSSI HFWSSLSPVA PLSPARLQGP STLFQFPTLL NGHMPVPIPS LDRAASPVLL SSNSQKS // ID EVI1_HUMAN Reviewed; 1051 AA. AC Q03112; A1L4F3; A8KA00; B7Z8W7; B7ZLQ3; B7ZLQ4; C9JAK0; D3DNP7; AC Q16122; Q5HYI1; Q6MZS6; Q8NEI5; Q99917; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 17-APR-2007, sequence version 2. DT 11-NOV-2015, entry version 153. DE RecName: Full=MDS1 and EVI1 complex locus protein EVI1; DE AltName: Full=Ecotropic virus integration site 1 protein homolog; DE Short=EVI-1; GN Name=MECOM; Synonyms=EVI1; 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 ALTERNATIVE SPLICING. RX PubMed=2115646; RA Morishita K., Parganas E., Douglass E.C., Ihle J.N.; RT "Unique expression of the human Evi-1 gene in an endometrial carcinoma RT cell line: sequence of cDNAs and structure of alternatively spliced RT transcripts."; RL Oncogene 5:963-971(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), AND CHROMOSOMAL TRANSLOCATION RP WITH RUNX1 IN CHRONIC MYELOCYTIC LEUKEMIA. RX PubMed=8313895; RA Mitani K., Ogawa S., Tanaka T., Miyoshi H., Kurokawa M., Mano H., RA Yazaki Y., Ohki M., Hirai H.; RT "Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) RT causes blastic crisis in chronic myelocytic leukemia."; RL EMBO J. 13:504-510(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE [LARGE RP SCALE MRNA] OF 1-759 (ISOFORM 2). RC TISSUE=Trachea; 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 5). RC TISSUE=Adipose tissue, and Fetal kidney; 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=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 6), AND RP NUCLEOTIDE SEQUENCE [MRNA] OF 516-1051 (ISOFORM 5). 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 970-1007 (ISOFORM 1). RX PubMed=8700545; RA Ogawa S., Kurokawa M., Tanaka T., Mitani K., Inazawa J., Hangaishi A., RA Tanaka K., Matsuo Y., Minowada J., Tsubota T., Yazaki Y., Hirai H.; RT "Structurally altered Evi-1 protein generated in the 3q21q26 RT syndrome."; RL Oncogene 13:183-191(1996). RN [9] RP FUNCTION IN TGF-BETA SIGNALING, INTERACTION WITH SMAD3 AND SMAD4, AND RP SUBCELLULAR LOCATION. RX PubMed=9665135; DOI=10.1038/27945; RA Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., RA Yazaki Y., Matsumoto K., Hirai H.; RT "The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting RT Smad3."; RL Nature 394:92-96(1998). RN [10] RP FUNCTION, AND INTERACTION WITH MAPK8 AND MAPK9. RX PubMed=10856240; DOI=10.1093/emboj/19.12.2958; RA Kurokawa M., Mitani K., Yamagata T., Takahashi T., Izutsu K., RA Ogawa S., Moriguchi T., Nishida E., Yazaki Y., Hirai H.; RT "The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents RT stress-induced cell death."; RL EMBO J. 19:2958-2968(2000). RN [11] RP FUNCTION, ACETYLATION, INTERACTION WITH CREBBP; CTBP1; KAT2B AND RP HISTONE DEACETYLASES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP 555-ASP-LEU-556 AND 586-ASP-LEU-587. 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 [12] RP FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), RP HOMOOLIGOMERIZATION, INTERACTION WITH CTBP1 AND SMAD3, AND SUBCELLULAR RP LOCATION. 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 [13] RP IDENTIFICATION 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 [14] RP FUNCTION IN APOPTOSIS. RX PubMed=16462766; DOI=10.1038/sj.onc.1209403; RA Liu Y., Chen L., Ko T.C., Fields A.P., Thompson E.A.; RT "Evi1 is a survival factor which conveys resistance to both TGFbeta- RT and taxol-mediated cell death via PI3K/AKT."; RL Oncogene 25:3565-3575(2006). RN [15] RP IDENTIFICATION 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 [16] RP FUNCTION. RX PubMed=19767769; DOI=10.1038/onc.2009.288; RA Shimabe M., Goyama S., Watanabe-Okochi N., Yoshimi A., Ichikawa M., RA Imai Y., Kurokawa M.; RT "Pbx1 is a downstream target of Evi-1 in hematopoietic RT stem/progenitors and leukemic cells."; RL Oncogene 28:4364-4374(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-860, 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 [18] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2; LYS-367; LYS-497; RP LYS-533; LYS-547; LYS-564; LYS-599; LYS-948; LYS-953 AND LYS-973, RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-190 (ISOFORM 2), SUMOYLATION RP [LARGE SCALE ANALYSIS] AT LYS-66 (ISOFORM 4), 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: Functions as a transcriptional regulator binding to DNA CC sequences in the promoter region of target genes and regulating CC positively or negatively their expression. Oncogene which plays a CC role in development, cell proliferation and differentiation. May CC also play a role in apoptosis through regulation of the JNK and CC TGF-beta signaling. Involved in hematopoiesis. CC {ECO:0000269|PubMed:10856240, ECO:0000269|PubMed:11568182, CC ECO:0000269|PubMed:15897867, ECO:0000269|PubMed:16462766, CC ECO:0000269|PubMed:19767769, ECO:0000269|PubMed:9665135}. CC -!- SUBUNIT: Homooligomer. Interacts with SUV39H1 (via SET domain); CC enhances MECOM transcriptional repression activity (By CC similarity). Interacts with CTBP1. Interacts with SMAD3 (via MH2 CC domain); the interaction is direct. Interacts with SMAD4; through CC interaction with SMAD3. Interacts with CREBBP, KAT2B and histone CC deacetylases. Interacts with MAPK8 and MAPK9; inhibits JNK CC signaling. {ECO:0000250, ECO:0000269|PubMed:10856240, CC ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:15897867, CC ECO:0000269|PubMed:9665135}. CC -!- INTERACTION: CC P56546:Ctbp2 (xeno); NbExp=3; IntAct=EBI-1384862, EBI-1384883; CC Q96EB6:SIRT1; NbExp=2; IntAct=EBI-1384862, EBI-1802965; CC Q9UBK9:UXT; NbExp=5; IntAct=EBI-1384862, EBI-357355; CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=Long, Evi-1a; CC IsoId=Q03112-1; Sequence=Displayed; CC Name=2; Synonyms=Evi-1c, Mds1/Evi1; CC IsoId=Q03112-3; Sequence=VSP_038733; 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 {ECO:0000244|PubMed:25218447}; CC Name=3; Synonyms=Mds1; CC IsoId=Q13465-1; Sequence=External; CC Note=Produced by alternative promoter usage.; CC Name=4; CC IsoId=Q03112-4; Sequence=VSP_038734, VSP_038735; CC Note=Contains a glycyl lysine isopeptide (Lys-Gly) (interchain CC with G-Cter in SUMO2) at position 66. CC {ECO:0000244|PubMed:25218447}; CC Name=5; CC IsoId=Q03112-5; Sequence=VSP_038736; CC Name=6; CC IsoId=Q03112-6; Sequence=VSP_038735, VSP_038736; CC -!- DOMAIN: Both zinc finger regions are required for the CC transcriptional activation of PBX1. CC -!- PTM: Phosphorylated. {ECO:0000250}. CC -!- PTM: May be acetylated by CREBBP and KAT2B. CC {ECO:0000269|PubMed:11568182}. CC -!- DISEASE: Note=A chromosomal aberration involving EVI1 is a cause CC of chronic myelogenous leukemia (CML). Translocation CC t(3;21)(q26;q22) with RUNX1/AML1. CC -!- SIMILARITY: Contains 10 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB29907.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAB37456.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC Sequence=AAI30521.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAH14103.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; 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; X54989; CAA38735.1; -; mRNA. DR EMBL; S69002; AAB29907.1; ALT_INIT; mRNA. DR EMBL; AK292865; BAF85554.1; -; mRNA. DR EMBL; AK304098; BAH14103.1; ALT_SEQ; mRNA. DR EMBL; BX640908; CAE45952.1; -; mRNA. DR EMBL; BX647613; CAI46086.1; -; mRNA. DR EMBL; AC007849; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC024099; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC069220; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC074033; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC078985; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW78553.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78556.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78557.1; -; Genomic_DNA. DR EMBL; BC031019; AAH31019.1; -; mRNA. DR EMBL; BC130520; AAI30521.1; ALT_INIT; mRNA. DR EMBL; BC143951; AAI43952.1; -; mRNA. DR EMBL; BC143952; AAI43953.1; -; mRNA. DR EMBL; S82592; AAB37456.1; ALT_SEQ; mRNA. DR CCDS; CCDS3205.1; -. [Q03112-1] DR CCDS; CCDS54669.1; -. [Q03112-5] DR CCDS; CCDS54670.1; -. [Q03112-4] DR PIR; A60191; A60191. DR PIR; S41705; S41705. DR RefSeq; NP_001098547.3; NM_001105077.3. [Q03112-4] DR RefSeq; NP_001098548.2; NM_001105078.3. [Q03112-1] DR RefSeq; NP_001157471.1; NM_001163999.1. [Q03112-6] DR RefSeq; NP_001157472.1; NM_001164000.1. [Q03112-5] DR RefSeq; NP_001192123.1; NM_001205194.1. [Q03112-1] DR RefSeq; NP_004982.2; NM_004991.3. [Q03112-3] DR RefSeq; NP_005232.2; NM_005241.3. [Q03112-1] DR RefSeq; XP_005247276.1; XM_005247219.2. DR RefSeq; XP_005247277.1; XM_005247220.2. DR RefSeq; XP_005247278.1; XM_005247221.2. DR RefSeq; XP_005247280.1; XM_005247223.2. [Q03112-1] DR RefSeq; XP_011510849.1; XM_011512547.1. [Q03112-4] DR RefSeq; XP_011510850.1; XM_011512548.1. [Q03112-4] DR UniGene; Hs.744090; -. DR ProteinModelPortal; Q03112; -. DR SMR; Q03112; 19-237, 733-813. DR BioGrid; 108423; 21. DR DIP; DIP-38639N; -. DR IntAct; Q03112; 3. DR STRING; 9606.ENSP00000264674; -. DR PhosphoSite; Q03112; -. DR BioMuta; ARHGAP32; -. DR DMDM; 145559472; -. DR MaxQB; Q03112; -. DR PaxDb; Q03112; -. DR PRIDE; Q03112; -. DR DNASU; 2122; -. DR Ensembl; ENST00000264674; ENSP00000264674; ENSG00000085276. [Q03112-4] DR Ensembl; ENST00000464456; ENSP00000419770; ENSG00000085276. [Q03112-5] DR Ensembl; ENST00000468789; ENSP00000419995; ENSG00000085276. [Q03112-1] DR Ensembl; ENST00000628990; ENSP00000486104; ENSG00000085276. [Q03112-1] DR GeneID; 2122; -. DR KEGG; hsa:2122; -. DR UCSC; uc003ffi.3; human. [Q03112-1] DR UCSC; uc003ffj.3; human. [Q03112-4] DR UCSC; uc003ffk.2; human. [Q03112-5] DR UCSC; uc011bpi.1; human. [Q03112-6] DR UCSC; uc011bpj.1; human. [Q03112-3] DR CTD; 2122; -. DR GeneCards; MECOM; -. DR H-InvDB; HIX0003836; -. DR HGNC; HGNC:3498; MECOM. DR HPA; HPA046537; -. DR HPA; HPA052977; -. DR MIM; 165215; gene. DR neXtProt; NX_Q03112; -. DR Orphanet; 402020; 'Acute myeloid leukemia with inv3(p21;q26.2) or t(3;3)(p21;q26.2)'. DR Orphanet; 52688; Myelodysplastic syndrome. DR PharmGKB; PA27912; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00530000063676; -. DR HOVERGEN; HBG005619; -. DR InParanoid; Q03112; -. DR KO; K04462; -. DR OrthoDB; EOG72G16H; -. DR PhylomeDB; Q03112; -. DR TreeFam; TF315309; -. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR SignaLink; Q03112; -. DR ChiTaRS; MECOM; human. DR GeneWiki; MECOM; -. DR GenomeRNAi; 2122; -. DR NextBio; 8579; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; Q03112; -. DR CleanEx; HS_EVI1; -. DR ExpressionAtlas; Q03112; baseline and differential. DR Genevisible; Q03112; HS. DR GO; GO:0016235; C:aggresome; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0006325; P:chromatin organization; TAS:Reactome. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl. DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0071425; P:hematopoietic stem cell proliferation; ISS:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl. DR GO; GO:0046329; P:negative regulation of JNK cascade; IMP:UniProtKB. DR GO; GO:0043069; P:negative regulation of programmed cell death; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0001780; P:neutrophil homeostasis; IEA:Ensembl. DR GO; GO:0060039; P:pericardium development; IEA:Ensembl. DR GO; GO:0090336; P:positive regulation of brown fat cell differentiation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0072001; P:renal system development; IEA:Ensembl. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR GO; GO:0019827; P:stem cell population maintenance; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 8. DR InterPro; IPR030413; Evi1/Prdm16. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR PANTHER; PTHR24393; PTHR24393; 1. DR Pfam; PF00096; zf-C2H2; 3. DR SMART; SM00355; ZnF_C2H2; 10. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 8. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 10. PE 1: Evidence at protein level; KW Acetylation; Alternative promoter usage; Alternative splicing; KW Apoptosis; Chromosomal rearrangement; Complete proteome; KW Developmental protein; Differentiation; DNA-binding; Isopeptide bond; KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 1051 MDS1 and EVI1 complex locus protein EVI1. FT /FTId=PRO_0000047273. FT ZN_FING 21 44 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 75 97 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 103 125 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 131 154 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 160 182 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 188 210 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 217 239 C2H2-type 7. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 733 755 C2H2-type 8. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 761 784 C2H2-type 9. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 790 812 C2H2-type 10. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 1 252 Interaction with MAPK9, SMAD3 and FT probably SUV39H1. FT MOTIF 421 434 Nuclear localization signal. FT {ECO:0000255}. FT MOTIF 553 557 CTBP-binding motif 1. {ECO:0000250}. FT MOTIF 584 588 CTBP-binding motif 2. {ECO:0000250}. FT COMPBIAS 886 937 Asp/Glu-rich (acidic). FT MOD_RES 436 436 Phosphoserine. FT {ECO:0000250|UniProtKB:P14404}. FT MOD_RES 552 552 Phosphoserine. FT {ECO:0000250|UniProtKB:P14404}. FT MOD_RES 860 860 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT CROSSLNK 2 2 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 367 367 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 497 497 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 533 533 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 547 547 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 564 564 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 599 599 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 948 948 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 953 953 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 973 973 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 1 1 M -> MRSKGRARKLATNNECVYGNYPEIPLEEMPDADGVA FT STPSLNIQEPCSPATSSEAFTPKEGSPYKAPIYIPDDIPIP FT AEFELRESNMPGAGLGIWTKRKIEVGEKFGPYVGEQRSNLK FT DPSYGWEILDEFYNVKFCIDASQPDVGSWLKYIRFAGCYDQ FT HNLVACQINDQIFYRVVADIAPGEELLLFM (in FT isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_038733. FT VAR_SEQ 1 1 M -> MILDEFYNVKFCIDASQPDVGSWLKYIRFAGCYDQH FT NLVACQINDQIFYRVVADIAPGEELLLFM (in isoform FT 4). {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_038734. FT VAR_SEQ 138 138 K -> KQ (in isoform 4 and isoform 6). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_038735. FT VAR_SEQ 672 680 Missing (in isoform 5 and isoform 6). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005, FT ECO:0000303|PubMed:8313895}. FT /FTId=VSP_038736. FT VARIANT 107 107 Q -> R (in dbSNP:rs34896995). FT /FTId=VAR_061928. FT MUTAGEN 555 556 DL->AS: Partial loss of interaction with FT CTBP1. Loss of interaction with CTBP1; FT when associated with 586-A-S-587. FT {ECO:0000269|PubMed:11568182}. FT MUTAGEN 586 587 DL->AS: Partial loss of interaction with FT CTBP1. Loss of interaction with CTBP1; FT when associated with 555-A-S-556. FT {ECO:0000269|PubMed:11568182}. FT CONFLICT 20 20 Q -> R (in Ref. 4; CAE45952). FT {ECO:0000305}. FT CONFLICT 175 175 L -> P (in Ref. 4; CAE45952). FT {ECO:0000305}. FT CONFLICT 301 301 F -> S (in Ref. 3; BAF85554). FT {ECO:0000305}. FT CONFLICT 303 303 F -> V (in Ref. 1; CAA38735). FT {ECO:0000305}. FT CONFLICT 443 443 S -> P (in Ref. 4; CAI46086). FT {ECO:0000305}. FT CONFLICT 543 543 K -> R (in Ref. 4; CAE45952). FT {ECO:0000305}. FT CONFLICT 730 730 K -> R (in Ref. 3; BAF85554). FT {ECO:0000305}. FT CONFLICT 741 741 I -> V (in Ref. 4; CAI46086). FT {ECO:0000305}. FT CONFLICT 796 796 D -> Y (in Ref. 1; CAA38735). FT {ECO:0000305}. FT CONFLICT 875 875 D -> E (in Ref. 1; CAA38735). FT {ECO:0000305}. FT CONFLICT 881 881 T -> P (in Ref. 1; CAA38735). FT {ECO:0000305}. FT CONFLICT 906 906 N -> Y (in Ref. 1; CAA38735). FT {ECO:0000305}. FT CONFLICT 992 992 V -> A (in Ref. 3; BAF85554). FT {ECO:0000305}. FT CONFLICT 1013 1013 L -> P (in Ref. 4; CAE45952). FT {ECO:0000305}. SQ SEQUENCE 1051 AA; 118276 MW; BD132C53EA08D263 CRC64; MKSEDYPHET MAPDIHEERQ YRCEDCDQLF ESKAELADHQ KFPCSTPHSA FSMVEEDFQQ KLESENDLQE IHTIQECKEC DQVFPDLQSL EKHMLSHTEE REYKCDQCPK AFNWKSNLIR HQMSHDSGKH YECENCAKVF TDPSNLQRHI RSQHVGARAH ACPECGKTFA TSSGLKQHKH IHSSVKPFIC EVCHKSYTQF SNLCRHKRMH ADCRTQIKCK DCGQMFSTTS SLNKHRRFCE GKNHFAAGGF FGQGISLPGT PAMDKTSMVN MSHANPGLAD YFGANRHPAG LTFPTAPGFS FSFPGLFPSG LYHRPPLIPA SSPVKGLSST EQTNKSQSPL MTHPQILPAT QDILKALSKH PSVGDNKPVE LQPERSSEER PFEKISDQSE SSDLDDVSTP SGSDLETTSG SDLESDIESD KEKFKENGKM FKDKVSPLQN LASINNKKEY SNHSIFSPSL EEQTAVSGAV NDSIKAIASI AEKYFGSTGL VGLQDKKVGA LPYPSMFPLP FFPAFSQSMY PFPDRDLRSL PLKMEPQSPG EVKKLQKGSS ESPFDLTTKR KDEKPLTPVP SKPPVTPATS QDQPLDLSMG SRSRASGTKL TEPRKNHVFG GKKGSNVESR PASDGSLQHA RPTPFFMDPI YRVEKRKLTD PLEALKEKYL RPSPGFLFHP QFQLPDQRTW MSAIENMAEK LESFSALKPE ASELLQSVPS MFNFRAPPNA LPENLLRKGK ERYTCRYCGK IFPRSANLTR HLRTHTGEQP YRCKYCDRSF SISSNLQRHV RNIHNKEKPF KCHLCDRCFG QQTNLDRHLK KHENGNMSGT ATSSPHSELE STGAILDDKE DAYFTEIRNF IGNSNHGSQS PRNVEERMNG SHFKDEKALV TSQNSDLLDD EEVEDEVLLD EEDEDNDITG KTGKEPVTSN LHEGNPEDDY EETSALEMSC KTSPVRYKEE EYKSGLSALD HIRHFTDSLK MRKMEDNQYS EAELSSFSTS HVPEELKQPL HRKSKSQAYA MMLSLSDKES LHSTSHSSSN VWHSMARAAA ESSAIQSISH V // ID FOG1_HUMAN Reviewed; 1006 AA. AC Q8IX07; DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 11-NOV-2015, entry version 120. DE RecName: Full=Zinc finger protein ZFPM1; DE AltName: Full=Friend of GATA protein 1; DE Short=FOG-1; DE Short=Friend of GATA 1; DE AltName: Full=Zinc finger protein 89A; DE AltName: Full=Zinc finger protein multitype 1; GN Name=ZFPM1; Synonyms=FOG1, ZFN89A; 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], TISSUE SPECIFICITY, AND INTERACTION WITH RP GATA1 AND GATA2. RC TISSUE=Megakaryocyte; RX PubMed=12483298; DOI=10.1007/s00439-002-0832-1; RA Freson K., Thys C., Wittewrongel C., Vermylen J., Hoylaerts M.F., RA Van Geet C.; RT "Molecular cloning and characterization of the GATA1 cofactor human RT FOG1 and assessment of its binding to GATA1 proteins carrying D218 RT substitutions."; RL Hum. Genet. 112:42-49(2003). RN [2] 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 [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 IDENTIFICATION 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 [5] 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-786, 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). RN [7] 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-901 AND SER-909, 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-671; SER-786; SER-901 RP AND SER-914, 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: Transcription regulator that plays an essential role in CC erythroid and megakaryocytic cell differentiation. Essential CC cofactor that acts via the formation of a heterodimer with CC transcription factors of the GATA family GATA1, GATA2 and GATA3. CC Such heterodimer can both activate or repress transcriptional CC activity, depending on the cell and promoter context. The CC heterodimer formed with GATA proteins is essential to activate CC expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, CC while it represses expression of KLF1. May be involved in CC regulation of some genes in gonads. May also be involved in CC cardiac development, in a non-redundant way with ZFPM2/FOG2 (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with corepressor CTBP2; this interaction is CC however not essential for corepressor activity (By similarity). CC Interacts with the N-terminal zinc-finger of GATA1, GATA2 and CC probably GATA3. {ECO:0000250, ECO:0000269|PubMed:12483298}. CC -!- INTERACTION: CC P49841:GSK3B; NbExp=2; IntAct=EBI-3942619, EBI-373586; CC Q09028:RBBP4; NbExp=4; IntAct=EBI-3942619, EBI-620823; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Mainly expressed in hematopoietic tissues. CC Also expressed in adult cerebellum, stomach, lymph node, liver and CC pancreas. Expressed in fetal heart, liver and spleen. CC {ECO:0000269|PubMed:12483298}. CC -!- DOMAIN: The CCHC-type zinc fingers 1, 5, 6 and 9 directly bind to CC GATA-type zinc fingers. The Tyr residue adjacent to the last Cys CC of the CCHC-type zinc finger is essential for the interaction with CC GATA-type zinc fingers (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the FOG (Friend of GATA) family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 4 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 5 C2HC-type zinc fingers. {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; AF488691; AAN45858.1; -; mRNA. DR EMBL; AC116552; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC135049; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471184; EAW66806.1; -; Genomic_DNA. DR CCDS; CCDS32502.1; -. DR RefSeq; NP_722520.2; NM_153813.2. DR UniGene; Hs.632218; -. DR PDB; 2XU7; X-ray; 1.90 A; C/D=1-15. DR PDBsum; 2XU7; -. DR ProteinModelPortal; Q8IX07; -. DR SMR; Q8IX07; 85-209, 315-347. DR BioGrid; 127806; 10. DR DIP; DIP-48415N; -. DR IntAct; Q8IX07; 3. DR STRING; 9606.ENSP00000326630; -. DR PhosphoSite; Q8IX07; -. DR BioMuta; ZFPM1; -. DR DMDM; 296434508; -. DR MaxQB; Q8IX07; -. DR PaxDb; Q8IX07; -. DR PRIDE; Q8IX07; -. DR Ensembl; ENST00000319555; ENSP00000326630; ENSG00000179588. DR GeneID; 161882; -. DR KEGG; hsa:161882; -. DR UCSC; uc002fkv.3; human. DR CTD; 161882; -. DR GeneCards; ZFPM1; -. DR HGNC; HGNC:19762; ZFPM1. DR HPA; HPA046603; -. DR MIM; 601950; gene. DR neXtProt; NX_Q8IX07; -. DR PharmGKB; PA134920282; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00530000063823; -. DR HOGENOM; HOG000112626; -. DR HOVERGEN; HBG101018; -. DR InParanoid; Q8IX07; -. DR KO; K17441; -. DR OMA; YSCPAAP; -. DR OrthoDB; EOG74TWXR; -. DR PhylomeDB; Q8IX07; -. DR TreeFam; TF331342; -. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR ChiTaRS; ZFPM1; human. DR GeneWiki; ZFPM1; -. DR GenomeRNAi; 161882; -. DR NextBio; 88126; -. DR PRO; PR:Q8IX07; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; Q8IX07; -. DR CleanEx; HS_ZFPM1; -. DR ExpressionAtlas; Q8IX07; baseline and differential. DR Genevisible; Q8IX07; HS. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005667; C:transcription factor complex; IDA:BHF-UCL. DR GO; GO:0017053; C:transcriptional repressor complex; IDA:BHF-UCL. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001085; F:RNA polymerase II transcription factor binding; IPI:BHF-UCL. DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:BHF-UCL. DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL. DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISS:BHF-UCL. DR GO; GO:0060318; P:definitive erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:BHF-UCL. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:BHF-UCL. DR GO; GO:0030851; P:granulocyte differentiation; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IBA:GO_Central. DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl. DR GO; GO:0030219; P:megakaryocyte differentiation; ISS:BHF-UCL. DR GO; GO:0003192; P:mitral valve formation; ISS:BHF-UCL. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:BHF-UCL. DR GO; GO:0045403; P:negative regulation of interleukin-4 biosynthetic process; IDA:BHF-UCL. DR GO; GO:0060377; P:negative regulation of mast cell differentiation; ISS:BHF-UCL. DR GO; GO:0032091; P:negative regulation of protein binding; ISS:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:GOC. DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0030220; P:platelet formation; IGI:BHF-UCL. DR GO; GO:0045078; P:positive regulation of interferon-gamma biosynthetic process; IDA:BHF-UCL. DR GO; GO:0060319; P:primitive erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0032642; P:regulation of chemokine production; IEA:Ensembl. DR GO; GO:0010724; P:regulation of definitive erythrocyte differentiation; IDA:BHF-UCL. DR GO; GO:0002295; P:T-helper cell lineage commitment; IC:BHF-UCL. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0071733; P:transcriptional activation by promoter-enhancer looping; ISS:BHF-UCL. DR GO; GO:0003195; P:tricuspid valve formation; ISS:BHF-UCL. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. DR Gene3D; 3.30.160.60; -; 2. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR SMART; SM00355; ZnF_C2H2; 9. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2. PE 1: Evidence at protein level; KW 3D-structure; Activator; Complete proteome; DNA-binding; KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 1006 Zinc finger protein ZFPM1. FT /FTId=PRO_0000221041. FT ZN_FING 241 264 C2HC-type 1. FT ZN_FING 290 314 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 320 342 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 348 371 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 577 699 C2HC-type 2. FT ZN_FING 683 705 C2HC-type 3. FT ZN_FING 817 839 C2HC-type 4. FT ZN_FING 854 877 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 974 1000 C2HC-type 5. FT REGION 330 341 Interaction with TACC3. {ECO:0000250}. FT REGION 794 800 Interaction with CTBP2. {ECO:0000250}. FT MOD_RES 128 128 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 272 272 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 491 491 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 494 494 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 671 671 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 786 786 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 901 901 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 909 909 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 914 914 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 935 935 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT VARIANT 70 70 G -> A (in dbSNP:rs34916016). FT /FTId=VAR_057491. FT CONFLICT 22 22 R -> G (in Ref. 1; AAN45858). FT {ECO:0000305}. FT CONFLICT 444 447 EPLA -> AP (in Ref. 1; AAN45858). FT {ECO:0000305}. SQ SEQUENCE 1006 AA; 104888 MW; E9C2363503A64898 CRC64; MSRRKQSNPR QIKRSLGDME AREEVQLVGA SHMEQKATAP EAPSPPSADV NSPPPLPPPT SPGGPKELEG QEPEPRPTEE EPGSPWSGPD ELEPVVQDGQ RRIRARLSLA TGLSWGPFHG SVQTRASSPR QAEPSPALTL LLVDEACWLR TLPQALTEAE ANTEIHRKDD ALWCRVTKPV PAGGLLSVLL TAEPHSTPGH PVKKEPAEPT CPAPAHDLQL LPQQAGMASI LATAVINKDV FPCKDCGIWY RSERNLQAHL LYYCASRQGT GSPAAAATDE KPKETYPNER VCPFPQCRKS CPSASSLEIH MRSHSGERPF VCLICLSAFT TKANCERHLK VHTDTLSGVC HSCGFISTTR DILYSHLVTN HMVCQPGSKG EIYSPGAGHP ATKLPPDSLG SFQQQHTALQ GPLASADLGL APTPSPGLDR KALAEATNGE ARAEPLAQNG GSSEPPAAPR SIKVEAVEEP EAAPILGPGE PGPQAPSRTP SPRSPAPARV KAELSSPTPG SSPVPGELGL AGALFLPQYV FGPDAAPPAS EILAKMSELV HSRLQQGAGA GAGGAQTGLF PGAPKGATCF ECEITFSNVN NYYVHKRLYC SGRRAPEDAP AARRPKAPPG PARAPPGQPA EPDAPRSSPG PGAREEGAGG AATPEDGAGG RGSEGSQSPG SSVDDAEDDP SRTLCEACNI RFSRHETYTV HKRYYCASRH DPPPRRPAAP PGPPGPAAPP APSPAAPVRT RRRRKLYELH AAGAPPPPPP GHAPAPESPR PGSGSGSGPG LAPARSPGPA ADGPIDLSKK PRRPLPGAPA PALADYHECT ACRVSFHSLE AYLAHKKYSC PAAPPPGALG LPAAACPYCP PNGPVRGDLL EHFRLAHGLL LGAPLAGPGV EARTPADRGP SPAPAPAASP QPGSRGPRDG LGPEPQEPPP GPPPSPAAAP EAVPPPPAPP SYSDKGVQTP SKGTPAPLPN GNHRYCRLCN IKFSSLSTFI AHKKYYCSSH AAEHVK // ID FOG2_HUMAN Reviewed; 1151 AA. AC Q8WW38; Q32MA6; Q9NPL7; Q9NPS4; Q9UNI5; DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 3. DT 11-NOV-2015, entry version 116. DE RecName: Full=Zinc finger protein ZFPM2; DE AltName: Full=Friend of GATA protein 2; DE Short=FOG-2; DE Short=Friend of GATA 2; DE Short=hFOG-2; DE AltName: Full=Zinc finger protein 89B; DE AltName: Full=Zinc finger protein multitype 2; GN Name=ZFPM2; Synonyms=FOG2, ZNF89B; 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), FUNCTION, TISSUE SPECIFICITY, RP INTERACTION WITH CTBP2, AND POSSIBLE INTERACTION WITH GATA1. RC TISSUE=Erythroleukemia; RX PubMed=10438528; DOI=10.1074/jbc.274.33.23491; RA Holmes M., Turner J., Fox A.H., Chisholm O., Crossley M., Chong B.; RT "hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 RT and modulates GATA-mediated activation."; RL J. Biol. Chem. 274:23491-23498(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Prostate; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-287 (ISOFORM 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 641-1151 (ISOFORM 1). RG The European IMAGE consortium; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP SUMOYLATION AT LYS-324; LYS-471; LYS-915 AND LYS-955, AND SUBCELLULAR RP LOCATION. RX PubMed=23226341; DOI=10.1371/journal.pone.0050637; RA Perdomo J., Jiang X.M., Carter D.R., Khachigian L.M., Chong B.H.; RT "SUMOylation regulates the transcriptional repression activity of FOG- RT 2 and its association with GATA-4."; RL PLoS ONE 7:E50637-E50637(2012). RN [5] RP INTERACTION WITH GATA4, INVOLVEMENT IN SRXY9, VARIANTS SRXY9 GLN-260; RP ARG-402 AND ILE-544, VARIANTS GLY-403 AND ASP-782, AND RP CHARACTERIZATION OF VARIANTS GLN-260 AND ARG-402. RX PubMed=24549039; DOI=10.1093/hmg/ddu074; RA Bashamboo A., Brauner R., Bignon-Topalovic J., Lortat-Jacob S., RA Karageorgou V., Lourenco D., Guffanti A., McElreavey K.; RT "Mutations in the FOG2/ZFPM2 gene are associated with anomalies of RT human testis determination."; RL Hum. Mol. Genet. 23:3657-3665(2014). RN [6] RP VARIANTS TOF GLY-30 AND GLY-657, AND CHARACTERIZATION OF VARIANTS TOF RP GLY-30 AND GLY-657. RX PubMed=14517948; DOI=10.1002/humu.10261; RA Pizzuti A., Sarkozy A., Newton A.L., Conti E., Flex E., Digilio M.C., RA Amati F., Gianni D., Tandoi C., Marino B., Crossley M., RA Dallapiccola B.; RT "Mutations of ZFPM2/FOG2 gene in sporadic cases of tetralogy of RT Fallot."; RL Hum. Mutat. 22:372-377(2003). RN [7] RP INVOLVEMENT IN DIH3. RX PubMed=16103912; DOI=10.1371/journal.pgen.0010010; RA Ackerman K.G., Herron B.J., Vargas S.O., Huang H., Tevosian S.G., RA Kochilas L., Rao C., Pober B.R., Babiuk R.P., Epstein J.A., RA Greer J.J., Beier D.R.; RT "Fog2 is required for normal diaphragm and lung development in mice RT and humans."; RL PLoS Genet. 1:58-65(2005). RN [8] RP VARIANT TOF ILE-544, AND VARIANTS CTHM GLY-30 AND VAL-227. RX PubMed=20807224; DOI=10.1111/j.1399-0004.2010.01523.x; RA De Luca A., Sarkozy A., Ferese R., Consoli F., Lepri F., Dentici M.L., RA Vergara P., De Zorzi A., Versacci P., Digilio M.C., Marino B., RA Dallapiccola B.; RT "New mutations in ZFPM2/FOG2 gene in tetralogy of Fallot and double RT outlet right ventricle."; RL Clin. Genet. 80:184-190(2011). CC -!- FUNCTION: Transcription regulator that plays a central role in CC heart morphogenesis and development of coronary vessels from CC epicardium, by regulating genes that are essential during CC cardiogenesis. Essential cofactor that acts via the formation of a CC heterodimer with transcription factors of the GATA family GATA4, CC GATA5 and GATA6. Such heterodimer can both activate or repress CC transcriptional activity, depending on the cell and promoter CC context. Also required in gonadal differentiation, possibly be CC regulating expression of SRY. Probably acts a corepressor of NR2F2 CC (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with the N-terminal zinc-finger of GATA4, GATA5 CC and probably GATA6. Interacts with retinoid nuclear receptor RXRA CC when ligand bound (By similarity). Interacts with corepressor CC CTBP2; this interaction is however not essential for corepressor CC activity. Able to bind GATA1 in vitro. Interacts with NR2F2 and CC NR2F6 (By similarity). Interacts with ATOH8; mediates indirect CC interaction with GATA4 (By similarity). CC {ECO:0000250|UniProtKB:Q8WW38, ECO:0000269|PubMed:10438528, CC ECO:0000269|PubMed:24549039}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23226341}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8WW38-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8WW38-2; Sequence=VSP_009701, VSP_009702; CC Note=Sequence incomplete. No experimental confirmation CC available.; CC -!- TISSUE SPECIFICITY: Widely expressed at low level. CC {ECO:0000269|PubMed:10438528}. CC -!- DOMAIN: The CCHC-type zinc fingers 1, 5, 6 and 8 directly bind to CC GATA-type zinc fingers. The Tyr residue adjacent to the last Cys CC of the CCHC-type zinc finger is essential for the interaction with CC GATA-type zinc fingers (By similarity). {ECO:0000250}. CC -!- PTM: Sumoylation reduces transcriptional repression activity. CC {ECO:0000269|PubMed:23226341}. CC -!- DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital CC heart anomaly which consists of pulmonary stenosis, ventricular CC septal defect, dextroposition of the aorta (aorta is on the right CC side instead of the left) and hypertrophy of the right ventricle. CC In this condition, blood from both ventricles (oxygen-rich and CC oxygen-poor) is pumped into the body often causing cyanosis. CC {ECO:0000269|PubMed:14517948, ECO:0000269|PubMed:20807224}. CC Note=The disease may be caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Diaphragmatic hernia 3 (DIH3) [MIM:610187]: Form of CC congenital diaphragmatic hernia (CDH). CDH refers to a group of CC congenital defects in the structural integrity of the diaphragm CC associated with often lethal pulmonary hypoplasia and pulmonary CC hypertension. {ECO:0000269|PubMed:16103912}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- DISEASE: 46,XY sex reversal 9 (SRXY9) [MIM:616067]: A disorder of CC sex development. Affected individuals have a 46,XY karyotype but CC present as phenotypically normal females or have ambiguous CC external genitalia. {ECO:0000269|PubMed:24549039}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A CC group of congenital heart defects involving the outflow tracts. CC Examples include truncus arteriosus communis, double-outlet right CC ventricle and transposition of great arteries. Truncus arteriosus CC communis is characterized by a single outflow tract instead of a CC separate aorta and pulmonary artery. In transposition of the great CC arteries, the aorta arises from the right ventricle and the CC pulmonary artery from the left ventricle. In double outlet of the CC right ventricle, both the pulmonary artery and aorta arise from CC the right ventricle. {ECO:0000269|PubMed:20807224}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the FOG (Friend of GATA) family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 3 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 5 C2HC-type zinc fingers. {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; AF119334; AAD49558.1; -; mRNA. DR EMBL; BC020928; AAH20928.1; -; mRNA. DR EMBL; BC109222; AAI09223.1; -; mRNA. DR EMBL; AL389987; CAB97539.1; -; mRNA. DR EMBL; AL389989; CAB97541.1; -; mRNA. DR CCDS; CCDS47908.1; -. [Q8WW38-1] DR RefSeq; NP_036214.2; NM_012082.3. [Q8WW38-1] DR UniGene; Hs.431009; -. DR ProteinModelPortal; Q8WW38; -. DR SMR; Q8WW38; 251-276, 290-325, 352-395, 548-574, 687-713, 1112-1145. DR BioGrid; 116986; 14. DR IntAct; Q8WW38; 2. DR STRING; 9606.ENSP00000384179; -. DR PhosphoSite; Q8WW38; -. DR BioMuta; ZFPM2; -. DR DMDM; 126302543; -. DR MaxQB; Q8WW38; -. DR PaxDb; Q8WW38; -. DR PRIDE; Q8WW38; -. DR Ensembl; ENST00000407775; ENSP00000384179; ENSG00000169946. [Q8WW38-1] DR GeneID; 23414; -. DR KEGG; hsa:23414; -. DR UCSC; uc003ymd.3; human. [Q8WW38-1] DR CTD; 23414; -. DR GeneCards; ZFPM2; -. DR HGNC; HGNC:16700; ZFPM2. DR HPA; HPA004094; -. DR MIM; 187500; phenotype. DR MIM; 217095; phenotype. DR MIM; 603693; gene. DR MIM; 610187; phenotype. DR MIM; 616067; phenotype. DR neXtProt; NX_Q8WW38; -. DR Orphanet; 251510; 46,XY partial gonadal dysgenesis. DR Orphanet; 2140; Congenital diaphragmatic hernia. DR Orphanet; 3303; Tetralogy of Fallot. DR PharmGKB; PA134947303; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00530000063823; -. DR HOGENOM; HOG000057275; -. DR HOVERGEN; HBG048953; -. DR InParanoid; Q8WW38; -. DR KO; K17442; -. DR OMA; IYSPLMP; -. DR OrthoDB; EOG74TWXR; -. DR PhylomeDB; Q8WW38; -. DR TreeFam; TF331342; -. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR ChiTaRS; ZFPM2; human. DR GeneWiki; ZFPM2; -. DR GenomeRNAi; 23414; -. DR NextBio; 45615; -. DR PRO; PR:Q8WW38; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; Q8WW38; -. DR CleanEx; HS_ZFPM2; -. DR ExpressionAtlas; Q8WW38; baseline and differential. DR Genevisible; Q8WW38; HS. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0001105; F:RNA polymerase II transcription coactivator activity; NAS:BHF-UCL. DR GO; GO:0001085; F:RNA polymerase II transcription factor binding; IBA:GO_Central. DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL. DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; NAS:BHF-UCL. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl. DR GO; GO:0007506; P:gonadal mesoderm development; IEA:UniProtKB-KW. DR GO; GO:0007507; P:heart development; IBA:GO_Central. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IEA:Ensembl. DR GO; GO:0060548; P:negative regulation of cell death; IEA:Ensembl. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:UniProtKB. DR GO; GO:2000195; P:negative regulation of female gonad development; 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; IDA:UniProtKB. DR GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:BHF-UCL. DR GO; GO:2000020; P:positive regulation of male gonad development; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0003221; P:right ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL. DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl. DR GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL. DR Gene3D; 3.30.160.60; -; 1. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR SMART; SM00355; ZnF_C2H2; 8. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Cardiomyopathy; Complete proteome; KW Differentiation; Disease mutation; DNA-binding; KW Gonadal differentiation; Isopeptide bond; Metal-binding; Nucleus; KW Polymorphism; Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 1151 Zinc finger protein ZFPM2. FT /FTId=PRO_0000221043. FT ZN_FING 250 273 C2HC-type 1. FT ZN_FING 296 320 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 335 357 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 363 385 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 548 571 C2HC-type 2. FT ZN_FING 687 710 C2HC-type 3. FT ZN_FING 854 877 C2HC-type 4. FT ZN_FING 1119 1142 C2HC-type 5. FT REGION 829 835 Interaction with CTBP2. {ECO:0000305}. FT MOTIF 736 740 Nuclear localization signal. FT {ECO:0000250}. FT CROSSLNK 324 324 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO1). FT CROSSLNK 471 471 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO1). FT CROSSLNK 915 915 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO1). FT CROSSLNK 955 955 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO1). FT VAR_SEQ 1 132 Missing (in isoform 2). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_009701. FT VAR_SEQ 247 287 KDIFPCKSCGIWYRSERNLQAHLMYYCSGRQREAAPVSEEN FT -> SKCSVLCSPALEVMGIYGRKKCLLTRNQEQTFFLQKKK FT KKK (in isoform 2). {ECO:0000303|Ref.3}. FT /FTId=VSP_009702. FT VARIANT 30 30 E -> G (in TOF and CTHM; does not affect FT its ability to interact with GATA4; FT dbSNP:rs121908601). FT {ECO:0000269|PubMed:14517948, FT ECO:0000269|PubMed:20807224}. FT /FTId=VAR_017942. FT VARIANT 227 227 I -> V (in CTHM). FT {ECO:0000269|PubMed:20807224}. FT /FTId=VAR_072074. FT VARIANT 260 260 R -> Q (in SRXY9; results in reduced FT transactivation activity on the AMH FT promoter; does not affect its ability to FT interact with GATA4). FT {ECO:0000269|PubMed:24549039}. FT /FTId=VAR_071104. FT VARIANT 402 402 S -> R (in SRXY9; results in reduced FT transactivation activity on the AMH FT promoter; abolished its ability to FT interact with GATA4). FT {ECO:0000269|PubMed:24549039}. FT /FTId=VAR_071105. FT VARIANT 403 403 A -> G (in dbSNP:rs11993776). FT {ECO:0000269|PubMed:24549039}. FT /FTId=VAR_024178. FT VARIANT 544 544 M -> I (in SRXY9 and TOF; reduced its FT ability to interact with GATA4). FT {ECO:0000269|PubMed:20807224, FT ECO:0000269|PubMed:24549039}. FT /FTId=VAR_072075. FT VARIANT 657 657 S -> G (in TOF; slightly impairs its FT ability to interact with GATA4; FT dbSNP:rs28374544). FT {ECO:0000269|PubMed:14517948}. FT /FTId=VAR_017943. FT VARIANT 782 782 E -> D (in dbSNP:rs2920048). FT {ECO:0000269|PubMed:24549039}. FT /FTId=VAR_017944. FT VARIANT 1055 1055 A -> V (in dbSNP:rs16873741). FT /FTId=VAR_030760. FT CONFLICT 198 198 F -> L (in Ref. 3; CAB97541). FT {ECO:0000305}. FT CONFLICT 939 939 L -> P (in Ref. 1; AAD49558). FT {ECO:0000305}. SQ SEQUENCE 1151 AA; 128159 MW; 680E31BA1D044C35 CRC64; MSRRKQSKPR QIKRPLEDAI EDEEEECPSE ETDIISKGDF PLEESFSTEF GPENLSCEEV EYFCNKGDDE GIQETAESDG DTQSEKPGQP GVETDDWDGP GELEVFQKDG ERKIQSRQQL PVGTTWGPFP GKMDLNNNSL KTKAQVPMVL TAGPKWLLDV TWQGVEDNKN NCIVYSKGGQ LWCTTTKAIS EGEELIAFVV DFDSRLQAAS QMTLTEGMYP ARLLDSIQLL PQQAAMASIL PTAIVNKDIF PCKSCGIWYR SERNLQAHLM YYCSGRQREA APVSEENEDS AHQISSLCPF PQCTKSFSNA RALEMHLNSH SGVKMEEFLP PGASLKCTVC SYTADSVINF HQHLFSHLTQ AAFRCNHCHF GFQTQRELLQ HQELHVPSGK LPRESDMEHS PSATEDSLQP ATDLLTRSEL PQSQKAMQTK DASSDTELDK CEKKTQLFLT NQRPEIQPTT NKQSFSYTKI KSEPSSPRLA SSPVQPNIGP SFPVGPFLSQ FSFPQDITMV PQASEILAKM SELVHRRLRH GSSSYPPVIY SPLMPKGATC FECNITFNNL DNYLVHKKHY CSSRWQQMAK SPEFPSVSEK MPEALSPNTG QTSINLLNPA AHSADPENPL LQTSCINSST VLDLIGPNGK GHDKDFSTQT KKLSTSSNND DKINGKPVDV KNPSVPLVDG ESDPNKTTCE ACNITFSRHE TYMVHKQYYC ATRHDPPLKR SASNKVPAMQ RTMRTRKRRK MYEMCLPEQE QRPPLVQQRF LDVANLNNPC TSTQEPTEGL GECYHPRCDI FPGIVSKHLE TSLTINKCVP VSKCDTTHSS VSCLEMDVPI DLSKKCLSQS ERTTTSPKRL LDYHECTVCK ISFNKVENYL AHKQNFCPVT AHQRNDLGQL DGKVFPNPES ERNSPDVSYE RSIIKCEKNG NLKQPSPNGN LFSSHLATLQ GLKVFSEAAQ LIATKEENRH LFLPQCLYPG AIKKAKGADQ LSPYYGIKPS DYISGSLVIH NTDIEQSRNA ENESPKGQAS SNGCAALKKD SLPLLPKNRG MVIVNGGLKQ DERPAANPQQ ENISQNPQHE DDHKSPSWIS ENPLAANENV SPGIPSAEEQ LSSIAKGVNG SSQAPTSGKY CRLCDIQFNN LSNFITHKKF YCSSHAAEHV K // ID HAIR_DROME Reviewed; 337 AA. AC P14003; A4V1N7; Q95NH3; Q95NU9; Q9VSN8; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 18-APR-2006, sequence version 2. DT 11-NOV-2015, entry version 154. DE RecName: Full=Protein hairy; GN Name=h; ORFNames=CG6494; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; OC Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT SER-292. RC STRAIN=Oregon-R; RX PubMed=2479541; RA Rushlow C.A., Hogan A., Pierchin S.M., Howe K.M., Lardelli M., RA Ish-Horowicz D.; RT "The Drosophila hairy protein acts in both segmentation and bristle RT patterning and shows homology to N-myc."; RL EMBO J. 8:3095-3103(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-21. RC STRAIN=R3-105, R3-107, R3-19, R3-2, R3-24, R3-48, R3-53, R3-6, R3-74, RC and R3-95; RX PubMed=12242230; RA Robin C., Lyman R.F., Long A.D., Langley C.H., Mackay T.F.C.; RT "hairy. A quantitative trait locus for Drosophila sensory bristle RT number."; RL Genetics 162:155-164(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [4] RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Embryo; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [6] RP DOMAIN WRPW MOTIF. RX PubMed=8001118; DOI=10.1016/0092-8674(94)90070-1; RA Paroush Z., Finley R.L. Jr., Kidd T., Wainwright S.M., Ingham P.W., RA Brent R., Ish-Horowicz D.; RT "Groucho is required for Drosophila neurogenesis, segmentation, and RT sex determination and interacts directly with hairy-related bHLH RT proteins."; RL Cell 79:805-815(1994). RN [7] RP FUNCTION, INTERACTION WITH GRO, AND DOMAIN WRPW MOTIF. RX PubMed=8649374; RA Fisher A.L., Ohsako S., Caudy M.; RT "The WRPW motif of the hairy-related basic helix-loop-helix repressor RT proteins acts as a 4-amino-acid transcription repression and protein- RT protein interaction domain."; RL Mol. Cell. Biol. 16:2670-2677(1996). RN [8] RP DNA-BINDING, INTERACTION WITH TOPORS, AND UBIQUITINATION. RX PubMed=14871887; DOI=10.1074/jbc.M310097200; RA Secombe J., Parkhurst S.M.; RT "Drosophila Topors is a RING finger-containing protein that functions RT as a ubiquitin-protein isopeptide ligase for the hairy basic helix- RT loop-helix repressor protein."; RL J. Biol. Chem. 279:17126-17133(2004). CC -!- FUNCTION: Pair-rule protein that regulates embryonic segmentation CC and adult bristle patterning. Transcriptional repressor of genes CC that require a bHLH protein for their transcription (e.g. the CC Fushi tarazu gene). {ECO:0000269|PubMed:8649374}. CC -!- SUBUNIT: Transcription repression requires formation of a complex CC with a corepressor protein (Groucho). Interacts with gro (via WPRW CC motif) and Topors. {ECO:0000269|PubMed:14871887, CC ECO:0000269|PubMed:8649374}. CC -!- INTERACTION: CC O46036:CtBP; NbExp=4; IntAct=EBI-123011, EBI-159330; CC Q9VNJ0:dgrn; NbExp=5; IntAct=EBI-123011, EBI-186615; CC P16371:gro; NbExp=3; IntAct=EBI-123011, EBI-153866; CC Q9V8P9:Topors; NbExp=4; IntAct=EBI-123011, EBI-147805; CC P83949:Ubx; NbExp=3; IntAct=EBI-123011, EBI-202590; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- DOMAIN: Has a particular type of basic domain (presence of a CC helix-interrupting proline) that binds to the N-box (CACNAG), CC rather than the canonical E-box (CANNTG). CC -!- DOMAIN: The C-terminal WRPW motif is a transcriptional repression CC domain necessary for the interaction with Groucho, a CC transcriptional corepressor recruited to specific target DNA by CC Hairy-related proteins. CC -!- PTM: Ubiquitinated by Topors. {ECO:0000269|PubMed:14871887}. CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00981}. CC -!- SIMILARITY: Contains 1 Orange domain. {ECO:0000255|PROSITE- CC ProRule:PRU00380}. 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; X15904; CAA34018.1; -; Genomic_DNA. DR EMBL; X15905; CAA34019.1; -; mRNA. DR EMBL; AY055833; AAL17767.1; -; Genomic_DNA. DR EMBL; AY055834; AAL17768.1; -; Genomic_DNA. DR EMBL; AY055835; AAL17769.1; -; Genomic_DNA. DR EMBL; AY055836; AAL17770.1; -; Genomic_DNA. DR EMBL; AY055837; AAL17771.1; -; Genomic_DNA. DR EMBL; AY055838; AAL17772.1; -; Genomic_DNA. DR EMBL; AY055839; AAL17773.1; -; Genomic_DNA. DR EMBL; AY055840; AAL17774.1; -; Genomic_DNA. DR EMBL; AY055841; AAL17775.1; -; Genomic_DNA. DR EMBL; AY055842; AAL17776.1; -; Genomic_DNA. DR EMBL; AE014296; AAF50378.1; -; Genomic_DNA. DR EMBL; AE014296; AAX52752.1; -; Genomic_DNA. DR EMBL; AY119633; AAM50287.1; -; mRNA. DR PIR; S06956; S06956. DR RefSeq; NP_001014577.1; NM_001014577.2. DR RefSeq; NP_523977.2; NM_079253.4. DR UniGene; Dm.2554; -. DR ProteinModelPortal; P14003; -. DR SMR; P14003; 23-92. DR BioGrid; 64402; 11. DR DIP; DIP-637N; -. DR IntAct; P14003; 8. DR MINT; MINT-1542874; -. DR STRING; 7227.FBpp0099504; -. DR PaxDb; P14003; -. DR GeneID; 38995; -. DR KEGG; dme:Dmel_CG6494; -. DR UCSC; CG6494-RA; d. melanogaster. DR CTD; 38995; -. DR FlyBase; FBgn0001168; h. DR eggNOG; KOG4304; Eukaryota. DR eggNOG; ENOG4111F0X; LUCA. DR InParanoid; P14003; -. DR KO; K09090; -. DR OMA; EEQPWRP; -. DR OrthoDB; EOG780RN7; -. DR PhylomeDB; P14003; -. DR Reactome; R-DME-210744; Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells. DR Reactome; R-DME-2122947; NOTCH1 Intracellular Domain Regulates Transcription. DR SignaLink; P14003; -. DR GenomeRNAi; 38995; -. DR NextBio; 811370; -. DR PRO; PR:P14003; -. DR Proteomes; UP000000803; Chromosome 3L. DR Bgee; P14003; -. DR Genevisible; P14003; DM. DR GO; GO:0005634; C:nucleus; IC:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0070888; F:E-box binding; IDA:FlyBase. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:FlyBase. DR GO; GO:0008134; F:transcription factor binding; IPI:FlyBase. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:FlyBase. DR GO; GO:0000902; P:cell morphogenesis; IMP:FlyBase. DR GO; GO:0061024; P:membrane organization; TAS:FlyBase. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:FlyBase. DR GO; GO:0007424; P:open tracheal system development; IMP:FlyBase. DR GO; GO:0007366; P:periodic partitioning by pair rule gene; NAS:FlyBase. DR GO; GO:0035289; P:posterior head segmentation; TAS:FlyBase. DR GO; GO:0007460; P:R8 cell fate commitment; NAS:FlyBase. DR GO; GO:0031323; P:regulation of cellular metabolic process; IMP:FlyBase. DR GO; GO:0001666; P:response to hypoxia; IMP:FlyBase. DR GO; GO:0007431; P:salivary gland development; TAS:FlyBase. DR GO; GO:0007435; P:salivary gland morphogenesis; IMP:FlyBase. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0035290; P:trunk segmentation; TAS:FlyBase. DR GO; GO:0035239; P:tube morphogenesis; IMP:FlyBase. DR Gene3D; 4.10.280.10; -; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR003650; Orange_dom. DR Pfam; PF07527; Hairy_orange; 1. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SMART; SM00511; ORANGE; 1. DR SUPFAM; SSF47459; SSF47459; 1. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS51054; ORANGE; 1. PE 1: Evidence at protein level; KW Complete proteome; Developmental protein; DNA-binding; Nucleus; KW Pair-rule protein; Polymorphism; Reference proteome; Repressor; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1 337 Protein hairy. FT /FTId=PRO_0000127181. FT DOMAIN 31 88 bHLH. {ECO:0000255|PROSITE- FT ProRule:PRU00981}. FT DOMAIN 107 136 Orange. {ECO:0000255|PROSITE- FT ProRule:PRU00380}. FT REGION 29 48 Interaction with Topors. FT MOTIF 334 337 WRPW motif. FT COMPBIAS 149 157 Gln-rich. FT COMPBIAS 222 237 Gln-rich. FT COMPBIAS 241 250 Poly-Ala. FT VARIANT 21 21 A -> S (in strain: R3-6, R3-105 and R3- FT 107). {ECO:0000269|PubMed:12242230}. FT VARIANT 292 292 P -> S. {ECO:0000269|PubMed:2479541}. SQ SEQUENCE 337 AA; 37005 MW; 49BECAF7F2D69FC4 CRC64; MVTGVTAANM TNVLGTAVVP AQLKETPLKS DRRSNKPIME KRRRARINNC LNELKTLILD ATKKDPARHS KLEKADILEK TVKHLQELQR QQAAMQQAAD PKIVNKFKAG FADCVNEVSR FPGIEPAQRR RLLQHLSNCI NGVKTELHQQ QRQQQQQSIH AQMLPSPPSS PEQDSQQGAA APYLFGIQQT ASGYFLPNGM QVIPTKLPNG SIALVLPQSL PQQQQQQLLQ HQQQQQQLAV AAAAAAAAAA QQQPMLVSMP QRTASTGSAS SHSSAGYESA PGSSSSCSYA PPSPANSSYE PMDIKPSVIQ RVPMEQQPLS LVIKKQIKEE EQPWRPW // ID HDAC4_HUMAN Reviewed; 1084 AA. AC P56524; E9PGB9; F5GX36; Q86YH7; Q9UND6; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 22-SEP-2009, sequence version 3. DT 11-NOV-2015, entry version 166. DE RecName: Full=Histone deacetylase 4; DE Short=HD4; DE EC=3.5.1.98; GN Name=HDAC4; Synonyms=KIAA0288; 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=Leukemia; RX PubMed=10220385; DOI=10.1073/pnas.96.9.4868; RA Grozinger C.M., Hassig C.A., Schreiber S.L.; RT "Three proteins define a class of human histone deacetylases related RT to yeast Hda1p."; RL Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9179496; DOI=10.1093/dnares/4.1.53; RA Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., RA Nomura N.; RT "Construction and characterization of human brain cDNA libraries RT suitable for analysis of cDNA clones encoding relatively large RT proteins."; RL DNA Res. 4:53-59(1997). RN [3] RP SEQUENCE REVISION TO N-TERMINUS. RA Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., RA Nomura N.; RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases. RN [4] 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 [5] 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 [6] 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 [7] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MEF2A. RX PubMed=10487761; DOI=10.1093/emboj/18.18.5099; RA Miska E.A., Karlsson C., Langley E., Nielsen S.J., Pines J., RA Kouzarides T.; RT "HDAC4 deacetylase associates with and represses the MEF2 RT transcription factor."; RL EMBO J. 18:5099-5107(1999). RN [8] RP FUNCTION, INTERACTION WITH MEF2C AND MEF2D, AND MUTAGENESIS OF RP HIS-803. RX PubMed=10523670; RA Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., RA Heng H.H., Th'ng J., Han J., Yang X.-J.; RT "HDAC4, a human histone deacetylase related to yeast HDA1, is a RT transcriptional corepressor."; RL Mol. Cell. Biol. 19:7816-7827(1999). RN [9] RP PHOSPHORYLATION AT SER-246; SER-467 AND SER-632, AND MUTAGENESIS OF RP SER-246; SER-467 AND SER-632. RX PubMed=10958686; DOI=10.1128/MCB.20.18.6904-6912.2000; RA Wang A.H., Kruhlak M.J., Wu J., Bertos N.R., Vezmar M., Posner B.I., RA Bazett-Jones D.P., Yang X.-J.; RT "Regulation of histone deacetylase 4 by binding of 14-3-3 proteins."; RL Mol. Cell. Biol. 20:6904-6912(2000). RN [10] RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-467 AND RP SER-632. RX PubMed=11470791; DOI=10.1074/jbc.M105086200; RA Zhao X., Ito A., Kane C.D., Liao T.-S., Bolger T.A., Lemrow S.M., RA Means A.R., Yao T.-P.; RT "The modular nature of histone deacetylase HDAC4 confers RT phosphorylation-dependent intracellular trafficking."; RL J. Biol. Chem. 276:35042-35048(2001). RN [11] RP NUCLEAR EXPORT SIGNAL, AND MUTAGENESIS OF VAL-1056 AND LEU-1062. RX PubMed=11509672; DOI=10.1128/MCB.21.18.6312-6321.2001; RA McKinsey T.A., Zhang C.-L., Olson E.N.; RT "Identification of a signal-responsive nuclear export sequence in RT class II histone deacetylases."; RL Mol. Cell. Biol. 21:6312-6321(2001). RN [12] RP INTERACTION WITH NR2C1. RX PubMed=11463856; DOI=10.1210/me.15.8.1318; RA Franco P.J., Farooqui M., Seto E., Wei L.-N.; RT "The orphan nuclear receptor TR2 interacts directly with both class I RT and class II histone deacetylases."; RL Mol. Endocrinol. 15:1318-1328(2001). RN [13] RP HOMODIMERIZATION, SUMOYLATION AT LYS-559, AND MUTAGENESIS OF LYS-559. RX PubMed=12032081; DOI=10.1093/emboj/21.11.2682; RA Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E., RA Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A.; RT "The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 RT deacetylase."; RL EMBO J. 21:2682-2691(2002). RN [14] RP INTERACTION WITH KDM5B. RX PubMed=17373667; DOI=10.1002/ijc.22673; RA Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K., RA Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., RA Freemont P., Taylor-Papadimitriou J.; RT "Breast cancer associated transcriptional repressor PLU-1/JARID1B RT interacts directly with histone deacetylases."; RL Int. J. Cancer 121:265-275(2007). RN [15] RP PHOSPHORYLATION BY CAMK2D. RX PubMed=17179159; DOI=10.1074/jbc.M604281200; RA Little G.H., Bai Y., Williams T., Poizat C.; RT "Nuclear calcium/calmodulin-dependent protein kinase IIdelta RT preferentially transmits signals to histone deacetylase 4 in cardiac RT cells."; RL J. Biol. Chem. 282:7219-7231(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632 AND SER-633, 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, 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 [18] RP INVOLVEMENT IN BDMR. RX PubMed=20691407; DOI=10.1016/j.ajhg.2010.07.011; RA Williams S.R., Aldred M.A., Der Kaloustian V.M., Halal F., Gowans G., RA McLeod D.R., Zondag S., Toriello H.V., Magenis R.E., Elsea S.H.; RT "Haploinsufficiency of HDAC4 causes brachydactyly mental retardation RT syndrome, with brachydactyly type E, developmental delays, and RT behavioral problems."; RL Am. J. Hum. Genet. 87:219-228(2010). RN [19] RP INTERACTION WITH MORC2. RX PubMed=20110259; DOI=10.1093/nar/gkq006; RA Shao Y., Li Y., Zhang J., Liu D., Liu F., Zhao Y., Shen T., Li F.; RT "Involvement of histone deacetylation in MORC2-mediated down- RT regulation of carbonic anhydrase IX."; RL Nucleic Acids Res. 38:2813-2824(2010). RN [20] 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 [21] 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). RN [22] RP FUNCTION, AND INTERACTION WITH EP300. RX PubMed=24413532; DOI=10.1158/0008-5472.CAN-13-2020; RA Kang H.J., Lee M.H., Kang H.L., Kim S.H., Ahn J.R., Na H., Na T.Y., RA Kim Y.N., Seong J.K., Lee M.O.; RT "Differential regulation of estrogen receptor alpha expression in RT breast cancer cells by metastasis-associated protein 1."; RL Cancer Res. 74:1484-1494(2014). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632, 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 [24] RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 343-359 IN COMPLEX WITH RP ANKRA2, AND PHOSPHORYLATION AT SER-350. RX PubMed=22649097; DOI=10.1126/scisignal.2002979; RA Xu C., Jin J., Bian C., Lam R., Tian R., Weist R., You L., Nie J., RA Bochkarev A., Tempel W., Tan C.S., Wasney G.A., Vedadi M., Gish G.D., RA Arrowsmith C.H., Pawson T., Yang X.J., Min J.; RT "Sequence-specific recognition of a PxLPxI/L motif by an ankyrin RT repeat tumbler lock."; RL Sci. Signal. 5:RA39-RA39(2012). RN [25] RP VARIANT [LARGE SCALE ANALYSIS] ARG-727. 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 [26] RP VARIANT ILE-754. RX PubMed=24169519; DOI=10.1038/ejhg.2013.243; RA Piton A., Poquet H., Redin C., Masurel A., Lauer J., Muller J., RA Thevenon J., Herenger Y., Chancenotte S., Bonnet M., Pinoit J.M., RA Huet F., Thauvin-Robinet C., Jaeger A.S., Le Gras S., Jost B., RA Gerard B., Peoc'h K., Launay J.M., Faivre L., Mandel J.L.; RT "20 ans apres: a second mutation in MAOA identified by targeted high- RT throughput sequencing in a family with altered behavior and RT cognition."; RL Eur. J. Hum. Genet. 22:776-783(2014). 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. Involved in muscle CC maturation via its interaction with the myocyte enhancer factors CC such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated CC epigenetic regulation of ESR1 expression in breast cancer. CC {ECO:0000269|PubMed:10523670, ECO:0000269|PubMed:24413532}. CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of CC a histone to yield a deacetylated histone. CC -!- SUBUNIT: Interacts with HDAC7 (By similarity). Homodimer. CC Homodimerization via its N-terminal domain. Interacts with MEF2C, CC AHRR, and NR2C1. Interacts with a 14-3-3 chaperone protein in a CC phosphorylation dependent manner. Interacts with BTBD14B (By CC similarity). Interacts with KDM5B. Interacts with MYOCD (By CC similarity). Interacts with MORC2. Interacts with ANKRA2. CC Interacts with EP300 in the presence of TFAP2C. {ECO:0000250, CC ECO:0000269|PubMed:10487761, ECO:0000269|PubMed:10523670, CC ECO:0000269|PubMed:11463856, ECO:0000269|PubMed:17373667, CC ECO:0000269|PubMed:20110259, ECO:0000269|PubMed:22649097, CC ECO:0000269|PubMed:24413532}. CC -!- INTERACTION: CC Q9H9E1:ANKRA2; NbExp=3; IntAct=EBI-308629, EBI-10215533; CC P10275:AR; NbExp=4; IntAct=EBI-308629, EBI-608057; CC P15336:ATF2; NbExp=2; IntAct=EBI-308629, EBI-1170906; CC P41182:BCL6; NbExp=3; IntAct=EBI-308629, EBI-765407; CC Q9HCU9:BRMS1; NbExp=2; IntAct=EBI-308629, EBI-714781; CC Q96JN2-2:CCDC136; NbExp=3; IntAct=EBI-308629, EBI-10171416; CC Q01850:CDR2; NbExp=3; IntAct=EBI-308629, EBI-1181367; CC O95967:EFEMP2; NbExp=3; IntAct=EBI-308629, EBI-743414; CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-308629, EBI-618309; CC P08393:ICP0 (xeno); NbExp=3; IntAct=EBI-308629, EBI-6148881; CC Q15323:KRT31; NbExp=3; IntAct=EBI-308629, EBI-948001; CC O76015:KRT38; NbExp=3; IntAct=EBI-308629, EBI-1047263; CC Q6A162:KRT40; NbExp=3; IntAct=EBI-308629, EBI-10171697; CC O95751:LDOC1; NbExp=3; IntAct=EBI-308629, EBI-740738; CC A9UHW6:MIF4GD; NbExp=4; IntAct=EBI-308629, EBI-373498; CC Q5JR59:MTUS2; NbExp=3; IntAct=EBI-308629, EBI-742948; CC Q8ND90:PNMA1; NbExp=3; IntAct=EBI-308629, EBI-302345; CC Q6NUQ1:RINT1; NbExp=3; IntAct=EBI-308629, EBI-726876; CC Q13761:RUNX3; NbExp=9; IntAct=EBI-308629, EBI-925990; CC P31947:SFN; NbExp=4; IntAct=EBI-308629, EBI-476295; CC P63279:UBE2I; NbExp=3; IntAct=EBI-308629, EBI-80168; CC P31946:YWHAB; NbExp=3; IntAct=EBI-308629, EBI-359815; CC P62258:YWHAE; NbExp=4; IntAct=EBI-308629, EBI-356498; CC P61981:YWHAG; NbExp=6; IntAct=EBI-308629, EBI-359832; CC Q04917:YWHAH; NbExp=3; IntAct=EBI-308629, EBI-306940; CC P63104:YWHAZ; NbExp=5; IntAct=EBI-308629, EBI-347088; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between CC the nucleus and the cytoplasm. Upon muscle cells differentiation, CC it accumulates in the nuclei of myotubes, suggesting a positive CC role of nuclear HDAC4 in muscle differentiation. The export to CC cytoplasm depends on the interaction with a 14-3-3 chaperone CC protein and is due to its phosphorylation at Ser-246, Ser-467 and CC Ser-632 by CaMK4 and SIK1. The nuclear localization probably CC depends on sumoylation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P56524-1; Sequence=Displayed; CC Name=2; CC IsoId=P56524-2; Sequence=VSP_057290, VSP_057291; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between CC the nucleus and the cytoplasm. CC -!- PTM: Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. CC Phosphorylation at other residues by CaMK2D is required for the CC interaction with 14-3-3. Phosphorylation at Ser-350 impairs the CC binding of ANKRA2 but generates a high-affinity docking site for CC 14-3-3. {ECO:0000269|PubMed:10958686, CC ECO:0000269|PubMed:22649097}. CC -!- PTM: Sumoylation on Lys-559 is promoted by the E3 SUMO-protein CC ligase RANBP2, and prevented by phosphorylation by CaMK4. CC {ECO:0000269|PubMed:12032081}. CC -!- DISEASE: Brachydactyly-mental retardation syndrome (BDMR) CC [MIM:600430]: A syndrome resembling the physical anomalies found CC in Albright hereditary osteodystrophy. Common features are mild CC facial dysmorphism, congenital heart defects, distinct CC brachydactyly type E, mental retardation, developmental delay, CC seizures, autism spectrum disorder, and stocky build. Soft tissue CC ossification is absent, and there are no abnormalities in CC parathyroid hormone or calcium metabolism. CC {ECO:0000269|PubMed:20691407}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA22957.2; Type=Erroneous initiation; 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; AF132607; AAD29046.1; -; mRNA. DR EMBL; AB006626; BAA22957.2; ALT_INIT; mRNA. DR EMBL; AC017028; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC062017; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF510800; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF510801; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471063; EAW71165.1; -; Genomic_DNA. DR EMBL; BC039904; AAH39904.1; -; mRNA. DR CCDS; CCDS2529.1; -. [P56524-1] DR RefSeq; NP_006028.2; NM_006037.3. [P56524-1] DR UniGene; Hs.20516; -. DR PDB; 2H8N; X-ray; 2.60 A; A/B/C/D=62-153. DR PDB; 2O94; X-ray; 3.00 A; A/B/C/D=62-153. DR PDB; 2VQJ; X-ray; 2.10 A; A=648-1057. DR PDB; 2VQM; X-ray; 1.80 A; A=648-1057. DR PDB; 2VQO; X-ray; 2.15 A; A/B=648-1057. DR PDB; 2VQQ; X-ray; 1.90 A; A/B=648-1057. DR PDB; 2VQV; X-ray; 3.30 A; A/B=648-1057. DR PDB; 2VQW; X-ray; 3.00 A; G=648-1057. DR PDB; 3UXG; X-ray; 1.85 A; B=343-359. DR PDB; 3UZD; X-ray; 1.86 A; B=343-359. DR PDB; 3V31; X-ray; 1.57 A; B=343-359. DR PDB; 4CBT; X-ray; 3.03 A; A/B/C=648-1033. DR PDB; 4CBY; X-ray; 2.72 A; A/B/C/D=648-1033. DR PDBsum; 2H8N; -. DR PDBsum; 2O94; -. DR PDBsum; 2VQJ; -. DR PDBsum; 2VQM; -. DR PDBsum; 2VQO; -. DR PDBsum; 2VQQ; -. DR PDBsum; 2VQV; -. DR PDBsum; 2VQW; -. DR PDBsum; 3UXG; -. DR PDBsum; 3UZD; -. DR PDBsum; 3V31; -. DR PDBsum; 4CBT; -. DR PDBsum; 4CBY; -. DR ProteinModelPortal; P56524; -. DR SMR; P56524; 62-129, 650-1051. DR BioGrid; 115106; 138. DR DIP; DIP-34565N; -. DR IntAct; P56524; 43. DR MINT; MINT-104901; -. DR STRING; 9606.ENSP00000264606; -. DR BindingDB; P56524; -. DR ChEMBL; CHEMBL3524; -. DR GuidetoPHARMACOLOGY; 2659; -. DR PhosphoSite; P56524; -. DR BioMuta; HDAC4; -. DR DMDM; 259016348; -. DR MaxQB; P56524; -. DR PaxDb; P56524; -. DR PRIDE; P56524; -. DR Ensembl; ENST00000345617; ENSP00000264606; ENSG00000068024. [P56524-1] DR Ensembl; ENST00000543185; ENSP00000440481; ENSG00000068024. [P56524-2] DR GeneID; 9759; -. DR KEGG; hsa:9759; -. DR UCSC; uc002vyk.4; human. [P56524-1] DR CTD; 9759; -. DR GeneCards; HDAC4; -. DR GeneReviews; HDAC4; -. DR HGNC; HGNC:14063; HDAC4. DR HPA; CAB004431; -. DR HPA; HPA048723; -. DR MIM; 600430; phenotype. DR MIM; 605314; gene. DR neXtProt; NX_P56524; -. DR Orphanet; 1001; 2q37 microdeletion syndrome. DR PharmGKB; PA29229; -. DR eggNOG; KOG1343; Eukaryota. DR eggNOG; COG0123; LUCA. DR GeneTree; ENSGT00530000062809; -. DR HOGENOM; HOG000232065; -. DR HOVERGEN; HBG057100; -. DR InParanoid; P56524; -. DR KO; K11406; -. DR OMA; SRQHESH; -. DR OrthoDB; EOG7RFTH5; -. DR PhylomeDB; P56524; -. DR TreeFam; TF106174; -. DR BRENDA; 3.5.1.98; 2681. 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 ChiTaRS; HDAC4; human. DR EvolutionaryTrace; P56524; -. DR GeneWiki; HDAC4; -. DR GenomeRNAi; 9759; -. DR NextBio; 35507317; -. DR PRO; PR:P56524; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; P56524; -. DR CleanEx; HS_HDAC4; -. DR ExpressionAtlas; P56524; baseline and differential. DR Genevisible; P56524; HS. DR GO; GO:0031672; C:A band; IEA:Ensembl. DR GO; GO:0042641; C:actomyosin; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0000118; C:histone deacetylase complex; IDA:BHF-UCL. DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0017053; C:transcriptional repressor complex; IDA:BHF-UCL. DR GO; GO:0030018; C:Z disc; IEA:Ensembl. DR GO; GO:0033613; F:activating transcription factor binding; IPI:BHF-UCL. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0001047; F:core promoter binding; IDA:UniProtKB. DR GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL. DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL. DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC. DR GO; GO:0030955; F:potassium ion binding; IDA:BHF-UCL. DR GO; GO:0033558; F:protein deacetylase activity; IDA:BHF-UCL. DR GO; GO:0070491; F:repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001025; F:RNA polymerase III transcription factor binding; IPI:UniProtKB. DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl. DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL. DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB. DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; TAS:BHF-UCL. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0006338; P:chromatin remodeling; IDA:BHF-UCL. DR GO; GO:0016575; P:histone deacetylation; IDA:BHF-UCL. DR GO; GO:0070932; P:histone H3 deacetylation; IDA:BHF-UCL. DR GO; GO:0070933; P:histone H4 deacetylation; IDA:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0045820; P:negative regulation of glycolytic process; ISS:BHF-UCL. DR GO; GO:0010832; P:negative regulation of myotube differentiation; IMP:BHF-UCL. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; 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; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB. DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl. DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB. DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IEA:Ensembl. DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IMP:BHF-UCL. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl. 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; ISS:BHF-UCL. DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IEA:Ensembl. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:UniProtKB. DR GO; GO:0043393; P:regulation of protein binding; IMP:BHF-UCL. DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; IEA:Ensembl. DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:BHF-UCL. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0070555; P:response to interleukin-1; IMP:BHF-UCL. DR GO; GO:0001501; P:skeletal system development; 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; IPR023801; His_deacetylse_dom. DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N. DR InterPro; IPR017320; Histone_deAcase_II_euk. DR PANTHER; PTHR10625; PTHR10625; 1. DR Pfam; PF12203; HDAC4_Gln; 1. DR Pfam; PF00850; Hist_deacetyl; 1. DR PIRSF; PIRSF037911; HDAC_II_euk; 1. DR PRINTS; PR01270; HDASUPER. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autism spectrum disorder; KW Chromatin regulator; Coiled coil; Complete proteome; Cytoplasm; KW Hydrolase; Isopeptide bond; Mental retardation; Metal-binding; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc. FT CHAIN 1 1084 Histone deacetylase 4. FT /FTId=PRO_0000114699. FT REGION 118 313 Interaction with MEF2A. FT REGION 655 1084 Histone deacetylase. FT COILED 67 177 {ECO:0000255}. FT MOTIF 1051 1084 Nuclear export signal. {ECO:0000250}. FT ACT_SITE 803 803 {ECO:0000250}. FT METAL 667 667 Zinc. {ECO:0000250}. FT METAL 669 669 Zinc. {ECO:0000250}. FT METAL 675 675 Zinc. {ECO:0000250}. FT METAL 751 751 Zinc. {ECO:0000250}. FT MOD_RES 210 210 Phosphoserine. FT {ECO:0000250|UniProtKB:Q6NZM9}. FT MOD_RES 246 246 Phosphoserine; by CaMK4 and SIK1. FT {ECO:0000269|PubMed:10958686}. FT MOD_RES 350 350 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:22649097}. FT MOD_RES 467 467 Phosphoserine; by CaMK4 and SIK1. FT {ECO:0000269|PubMed:10958686}. FT MOD_RES 565 565 Phosphoserine. FT {ECO:0000250|UniProtKB:Q6NZM9}. FT MOD_RES 632 632 Phosphoserine; by CaMK4. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:10958686}. FT MOD_RES 633 633 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT CROSSLNK 559 559 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 1 117 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_057290. FT VAR_SEQ 431 431 T -> TDWYLS (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_057291. FT VARIANT 727 727 P -> R (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036042. FT VARIANT 754 754 V -> I. {ECO:0000269|PubMed:24169519}. FT /FTId=VAR_071965. FT MUTAGEN 246 246 S->A: Reduces phosphorylation and its FT subsequent nuclear export. FT {ECO:0000269|PubMed:10958686}. FT MUTAGEN 467 467 S->A: Reduces phosphorylation and its FT subsequent nuclear export. FT {ECO:0000269|PubMed:10958686, FT ECO:0000269|PubMed:11470791}. FT MUTAGEN 559 559 K->R: Abolishes sumoylation and reduces FT the histone deacetylase activity. FT {ECO:0000269|PubMed:12032081}. FT MUTAGEN 632 632 S->A: Reduces phosphorylation and its FT subsequent nuclear export. FT {ECO:0000269|PubMed:10958686, FT ECO:0000269|PubMed:11470791}. FT MUTAGEN 803 803 H->L: Abolishes histone deacetylase FT activity. {ECO:0000269|PubMed:10523670}. FT MUTAGEN 1056 1056 V->A: Reduces CaMK-dependent nuclear FT export. {ECO:0000269|PubMed:11509672}. FT MUTAGEN 1062 1062 L->A: Reduces CaMK-dependent nuclear FT export. {ECO:0000269|PubMed:11509672}. FT CONFLICT 373 373 A -> T (in Ref. 1; AAD29046 and 2; FT BAA22957). {ECO:0000305}. FT HELIX 64 112 {ECO:0000244|PDB:2H8N}. FT HELIX 115 121 {ECO:0000244|PDB:2H8N}. FT TURN 122 125 {ECO:0000244|PDB:2H8N}. FT HELIX 126 128 {ECO:0000244|PDB:2H8N}. FT TURN 354 357 {ECO:0000244|PDB:3UXG}. FT STRAND 652 657 {ECO:0000244|PDB:2VQM}. FT HELIX 660 662 {ECO:0000244|PDB:2VQM}. FT STRAND 673 675 {ECO:0000244|PDB:2VQJ}. FT HELIX 681 691 {ECO:0000244|PDB:2VQM}. FT HELIX 694 697 {ECO:0000244|PDB:2VQM}. FT STRAND 698 701 {ECO:0000244|PDB:2VQM}. FT HELIX 708 711 {ECO:0000244|PDB:2VQM}. FT TURN 712 714 {ECO:0000244|PDB:2VQM}. FT HELIX 717 724 {ECO:0000244|PDB:2VQM}. FT HELIX 727 730 {ECO:0000244|PDB:2VQM}. FT HELIX 737 745 {ECO:0000244|PDB:2VQM}. FT STRAND 746 748 {ECO:0000244|PDB:2VQM}. FT STRAND 754 756 {ECO:0000244|PDB:2VQM}. FT HELIX 762 786 {ECO:0000244|PDB:2VQM}. FT STRAND 789 795 {ECO:0000244|PDB:2VQM}. FT STRAND 813 815 {ECO:0000244|PDB:2VQM}. FT HELIX 817 828 {ECO:0000244|PDB:2VQM}. FT STRAND 834 838 {ECO:0000244|PDB:2VQM}. FT STRAND 840 842 {ECO:0000244|PDB:2VQM}. FT HELIX 845 851 {ECO:0000244|PDB:2VQM}. FT STRAND 857 864 {ECO:0000244|PDB:2VQM}. FT HELIX 866 868 {ECO:0000244|PDB:2VQM}. FT STRAND 870 872 {ECO:0000244|PDB:4CBT}. FT HELIX 883 885 {ECO:0000244|PDB:2VQM}. FT STRAND 889 894 {ECO:0000244|PDB:2VQM}. FT STRAND 898 900 {ECO:0000244|PDB:2VQM}. FT HELIX 904 913 {ECO:0000244|PDB:2VQM}. FT HELIX 915 922 {ECO:0000244|PDB:2VQM}. FT STRAND 925 931 {ECO:0000244|PDB:2VQM}. FT STRAND 936 938 {ECO:0000244|PDB:2VQM}. FT TURN 940 943 {ECO:0000244|PDB:2VQM}. FT HELIX 950 961 {ECO:0000244|PDB:2VQM}. FT HELIX 964 966 {ECO:0000244|PDB:2VQM}. FT STRAND 968 972 {ECO:0000244|PDB:2VQM}. FT HELIX 978 992 {ECO:0000244|PDB:2VQM}. FT HELIX 1002 1006 {ECO:0000244|PDB:2VQM}. FT HELIX 1011 1025 {ECO:0000244|PDB:2VQM}. FT HELIX 1029 1031 {ECO:0000244|PDB:2VQM}. FT HELIX 1042 1047 {ECO:0000244|PDB:2VQM}. SQ SEQUENCE 1084 AA; 119040 MW; BB7FD37652D12398 CRC64; MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPSAVPMD LRLDHQFSLP VAEPALREQQ LQQELLALKQ KQQIQRQILI AEFQRQHEQL SRQHEAQLHE HIKQQQEMLA MKHQQELLEH QRKLERHRQE QELEKQHREQ KLQQLKNKEK GKESAVASTE VKMKLQEFVL NKKKALAHRN LNHCISSDPR YWYGKTQHSS LDQSSPPQSG VSTSYNHPVL GMYDAKDDFP LRKTASEPNL KLRSRLKQKV AERRSSPLLR RKDGPVVTAL KKRPLDVTDS ACSSAPGSGP SSPNNSSGSV SAENGIAPAV PSIPAETSLA HRLVAREGSA APLPLYTSPS LPNITLGLPA TGPSAGTAGQ QDAERLTLPA LQQRLSLFPG THLTPYLSTS PLERDGGAAH SPLLQHMVLL EQPPAQAPLV TGLGALPLHA QSLVGADRVS PSIHKLRQHR PLGRTQSAPL PQNAQALQHL VIQQQHQQFL EKHKQQFQQQ QLQMNKIIPK PSEPARQPES HPEETEEELR EHQALLDEPY LDRLPGQKEA HAQAGVQVKQ EPIESDEEEA EPPREVEPGQ RQPSEQELLF RQQALLLEQQ RIHQLRNYQA SMEAAGIPVS FGGHRPLSRA QSSPASATFP VSVQEPPTKP RFTTGLVYDT LMLKHQCTCG SSSSHPEHAG RIQSIWSRLQ ETGLRGKCEC IRGRKATLEE LQTVHSEAHT LLYGTNPLNR QKLDSKKLLG SLASVFVRLP CGGVGVDSDT IWNEVHSAGA ARLAVGCVVE LVFKVATGEL KNGFAVVRPP GHHAEESTPM GFCYFNSVAV AAKLLQQRLS VSKILIVDWD VHHGNGTQQA FYSDPSVLYM SLHRYDDGNF FPGSGAPDEV GTGPGVGFNV NMAFTGGLDP PMGDAEYLAA FRTVVMPIAS EFAPDVVLVS SGFDAVEGHP TPLGGYNLSA RCFGYLTKQL MGLAGGRIVL ALEGGHDLTA ICDASEACVS ALLGNELDPL PEKVLQQRPN ANAVRSMEKV MEIHSKYWRC LQRTTSTAGR SLIEAQTCEN EEAETVTAMA SLSVGVKPAE KRPDEEPMEE EPPL // ID HDAC5_HUMAN Reviewed; 1122 AA. AC Q9UQL6; C9JFV9; O60340; O60528; Q96DY4; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 11-NOV-2015, entry version 167. DE RecName: Full=Histone deacetylase 5; DE Short=HD5; DE EC=3.5.1.98; DE AltName: Full=Antigen NY-CO-9; GN Name=HDAC5; Synonyms=KIAA0600; 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). RX PubMed=10220385; DOI=10.1073/pnas.96.9.4868; RA Grozinger C.M., Hassig C.A., Schreiber S.L.; RT "Three proteins define a class of human histone deacetylases related RT to yeast Hda1p."; RL Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. RT The complete sequences of 100 new cDNA clones from brain which can RT code for large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [3] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). 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=Eye, 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-176 (ISOFORM 3). RC TISSUE=Neuroblastoma; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 189-1122 (ISOFORM 1). RC TISSUE=Colon carcinoma; RX PubMed=9610721; RX DOI=10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P; RA Scanlan M.J., Chen Y.-T., Williamson B., Gure A.O., Stockert E., RA Gordan J.D., Tuereci O., Sahin U., Pfreundschuh M., Old L.J.; RT "Characterization of human colon cancer antigens recognized by RT autologous antibodies."; RL Int. J. Cancer 76:652-658(1998). RN [8] RP GENE ORGANIZATION. RX PubMed=11018260; DOI=10.1016/S0167-4781(00)00191-3; RA Mahlknecht U., Schnittger S., Ottmann O.G., Schoch C., Mosebach M., RA Hiddemann W., Hoelzer D.; RT "Chromosomal organization and localization of the human histone RT deacetylase 5 gene (HDAC5)."; RL Biochim. Biophys. Acta 1493:342-348(2000). RN [9] RP INTERACTION WITH BCOR. RX PubMed=10898795; RA Huynh K.D., Fischle W., Verdin E., Bardwell V.J.; RT "BCoR, a novel corepressor involved in BCL-6 repression."; RL Genes Dev. 14:1810-1823(2000). RN [10] RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-259; RP SER-279; SER-498; SER-661 AND SER-713. RX PubMed=11081517; DOI=10.1038/35040593; RA McKinsey T.A., Zhang C.-L., Lu J., Olson E.N.; RT "Signal-dependent nuclear export of a histone deacetylase regulates RT muscle differentiation."; RL Nature 408:106-111(2000). RN [11] RP INTERACTION WITH 14-3-3, AND PHOSPHORYLATION AT SER-259 AND SER-498. RX PubMed=11114197; DOI=10.1073/pnas.260501497; RA McKinsey T.A., Zhang C.-L., Olson E.N.; RT "Activation of the myocyte enhancer factor-2 transcription factor by RT calcium/calmodulin-dependent protein kinase-stimulated binding of 14- RT 3-3 to histone deacetylase 5."; RL Proc. Natl. Acad. Sci. U.S.A. 97:14400-14405(2000). RN [12] RP NUCLEAR EXPORT SIGNAL, AND MUTAGENESIS OF VAL-1086 AND LEU-1092. RX PubMed=11509672; DOI=10.1128/MCB.21.18.6312-6321.2001; RA McKinsey T.A., Zhang C.-L., Olson E.N.; RT "Identification of a signal-responsive nuclear export sequence in RT class II histone deacetylases."; RL Mol. Cell. Biol. 21:6312-6321(2001). RN [13] RP UBIQUITINATION. RX PubMed=12354939; DOI=10.1073/pnas.172511699; RA Hook S.S., Orian A., Cowley S.M., Eisenman R.N.; RT "Histone deacetylase 6 binds polyubiquitin through its zinc finger RT (PAZ domain) and copurifies with deubiquitinating enzymes."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002). RN [14] RP INTERACTION WITH BCL6. RX PubMed=12504096; DOI=10.1016/S0006-291X(02)02873-5; RA Mascle X., Albagli O., Lemercier C.; RT "Point mutations in BCL6 DNA-binding domain reveal distinct roles for RT the six zinc fingers."; RL Biochem. Biophys. Res. Commun. 300:391-396(2003). RN [15] RP INTERACTION WITH KDM5B. RX PubMed=17373667; DOI=10.1002/ijc.22673; RA Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K., RA Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., RA Freemont P., Taylor-Papadimitriou J.; RT "Breast cancer associated transcriptional repressor PLU-1/JARID1B RT interacts directly with histone deacetylases."; RL Int. J. Cancer 121:265-275(2007). RN [16] RP INTERACTION WITH DDIT3. RX PubMed=17872950; DOI=10.1074/jbc.M703735200; RA Ohoka N., Hattori T., Kitagawa M., Onozaki K., Hayashi H.; RT "Critical and functional regulation of CHOP (C/EBP homologous protein) RT through the N-terminal portion."; RL J. Biol. Chem. 282:35687-35694(2007). RN [17] RP PHOSPHORYLATION AT SER-259 AND SER-498, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF SER-259 AND SER-498. RX PubMed=18184930; DOI=10.2337/db07-0843; RA McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., RA Schertzer J.D., Kemp B.E., Hargreaves M.; RT "AMP-activated protein kinase regulates GLUT4 transcription by RT phosphorylating histone deacetylase 5."; RL Diabetes 57:860-867(2008). RN [18] RP PHOSPHORYLATION AT SER-259 AND SER-498. RX PubMed=18332134; DOI=10.1074/jbc.M800264200; RA Ha C.H., Wang W., Jhun B.S., Wong C., Hausser A., Pfizenmaier K., RA McKinsey T.A., Olson E.N., Jin Z.G.; RT "Protein kinase D-dependent phosphorylation and nuclear export of RT histone deacetylase 5 mediates vascular endothelial growth factor- RT induced gene expression and angiogenesis."; RL J. Biol. Chem. 283:14590-14599(2008). RN [19] RP INTERACTION WITH BAHD1. RX PubMed=19666599; DOI=10.1073/pnas.0901259106; RA Bierne H., Tham T.N., Batsche E., Dumay A., Leguillou M., RA Kerneis-Golsteyn S., Regnault B., Seeler J.S., Muchardt C., RA Feunteun J., Cossart P.; RT "Human BAHD1 promotes heterochromatic gene silencing."; RL Proc. Natl. Acad. Sci. U.S.A. 106:13826-13831(2009). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-533, 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 [21] RP PHOSPHORYLATION AT THR-292, AND MUTAGENESIS OF SER-259; SER-291 AND RP THR-292. RX PubMed=20188095; DOI=10.1016/j.febslet.2010.02.057; RA Harrison B.C., Huynh K., Lundgaard G.L., Helmke S.M., Perryman M.B., RA McKinsey T.A.; RT "Protein kinase C-related kinase targets nuclear localization signals RT in a subset of class IIa histone deacetylases."; RL FEBS Lett. 584:1103-1110(2010). RN [22] 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 [23] RP FUNCTION, AND INTERACTION WITH EP300. RX PubMed=24413532; DOI=10.1158/0008-5472.CAN-13-2020; RA Kang H.J., Lee M.H., Kang H.L., Kim S.H., Ahn J.R., Na H., Na T.Y., RA Kim Y.N., Seong J.K., Lee M.O.; RT "Differential regulation of estrogen receptor alpha expression in RT breast cancer cells by metastasis-associated protein 1."; RL Cancer Res. 74:1484-1494(2014). RN [24] 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). 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. Involved in muscle CC maturation by repressing transcription of myocyte enhancer MEF2C. CC During muscle differentiation, it shuttles into the cytoplasm, CC allowing the expression of myocyte enhancer factors. Involved in CC the MTA1-mediated epigenetic regulation of ESR1 expression in CC breast cancer. {ECO:0000269|PubMed:24413532}. CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of CC a histone to yield a deacetylated histone. CC -!- SUBUNIT: Interacts with AHRR, BAHD1, BCOR, HDAC7, HDAC9, CTBP1, CC MEF2C, NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. CC Interacts with BCL6, DDIT3/CHOP, GRK5, KDM5B and MYOCD. Interacts CC with EP300 in the presence of TFAP2C. CC {ECO:0000269|PubMed:10898795, ECO:0000269|PubMed:11114197, CC ECO:0000269|PubMed:12504096, ECO:0000269|PubMed:17373667, CC ECO:0000269|PubMed:17872950, ECO:0000269|PubMed:19666599, CC ECO:0000269|PubMed:24413532}. CC -!- INTERACTION: CC Q9HCU9:BRMS1; NbExp=2; IntAct=EBI-715576, EBI-714781; CC P08393:ICP0 (xeno); NbExp=3; IntAct=EBI-715576, EBI-6148881; CC Q13761:RUNX3; NbExp=5; IntAct=EBI-715576, EBI-925990; CC P31947:SFN; NbExp=3; IntAct=EBI-715576, EBI-476295; CC P63104:YWHAZ; NbExp=2; IntAct=EBI-715576, EBI-347088; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between CC the nucleus and the cytoplasm. In muscle cells, it shuttles into CC the cytoplasm during myocyte differentiation. The export to CC cytoplasm depends on the interaction with a 14-3-3 chaperone CC protein and is due to its phosphorylation at Ser-259 and Ser-498 CC by AMPK, CaMK1 and SIK1. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9UQL6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UQL6-2; Sequence=VSP_002081; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q9UQL6-3; Sequence=VSP_039180; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between CC the nucleus and the cytoplasm. {ECO:0000250}. CC -!- PTM: Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-259 and CC Ser-498. The phosphorylation is required for the export to the CC cytoplasm and inhibition. Phosphorylated by the PKC kinases PKN1 CC and PKN2, impairing nuclear import. Phosphorylated by GRK5, CC leading to nuclear export of HDAC5 and allowing MEF2-mediated CC transcription (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated. Polyubiquitination however does not lead to CC its degradation. {ECO:0000269|PubMed:12354939}. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC18040.1; Type=Frameshift; Positions=1085; Evidence={ECO:0000305}; CC Sequence=BAA25526.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; 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; AF132608; AAD29047.1; -; mRNA. DR EMBL; AB011172; BAA25526.2; ALT_INIT; mRNA. DR EMBL; AC023855; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC013140; AAH13140.1; ALT_TERM; mRNA. DR EMBL; BC051824; AAH51824.1; -; mRNA. DR EMBL; BX458255; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AF039691; AAC18040.1; ALT_FRAME; mRNA. DR EMBL; BK000028; DAA00017.1; -; Genomic_DNA. DR CCDS; CCDS32663.1; -. [Q9UQL6-3] DR CCDS; CCDS45696.1; -. [Q9UQL6-1] DR RefSeq; NP_001015053.1; NM_001015053.1. [Q9UQL6-3] DR RefSeq; NP_005465.2; NM_005474.4. [Q9UQL6-1] DR RefSeq; XP_005256961.1; XM_005256904.3. [Q9UQL6-3] DR RefSeq; XP_005256963.1; XM_005256906.3. [Q9UQL6-1] DR UniGene; Hs.438782; -. DR ProteinModelPortal; Q9UQL6; -. DR SMR; Q9UQL6; 96-133, 681-1061. DR BioGrid; 115331; 343. DR DIP; DIP-38260N; -. DR IntAct; Q9UQL6; 28. DR MINT; MINT-1407477; -. DR STRING; 9606.ENSP00000225983; -. DR BindingDB; Q9UQL6; -. DR ChEMBL; CHEMBL3038483; -. DR GuidetoPHARMACOLOGY; 2660; -. DR PhosphoSite; Q9UQL6; -. DR BioMuta; HDAC5; -. DR DMDM; 296434519; -. DR MaxQB; Q9UQL6; -. DR PaxDb; Q9UQL6; -. DR PRIDE; Q9UQL6; -. DR Ensembl; ENST00000225983; ENSP00000225983; ENSG00000108840. [Q9UQL6-3] DR Ensembl; ENST00000336057; ENSP00000337290; ENSG00000108840. [Q9UQL6-2] DR Ensembl; ENST00000586802; ENSP00000468004; ENSG00000108840. [Q9UQL6-1] DR GeneID; 10014; -. DR KEGG; hsa:10014; -. DR UCSC; uc002ifd.1; human. [Q9UQL6-1] DR UCSC; uc002iff.1; human. [Q9UQL6-3] DR UCSC; uc010czp.1; human. [Q9UQL6-2] DR CTD; 10014; -. DR GeneCards; HDAC5; -. DR H-InvDB; HIX0013862; -. DR HGNC; HGNC:14068; HDAC5. DR HPA; CAB019400; -. DR HPA; HPA030991; -. DR MIM; 605315; gene. DR neXtProt; NX_Q9UQL6; -. DR PharmGKB; PA29230; -. DR eggNOG; KOG1343; Eukaryota. DR eggNOG; COG0123; LUCA. DR GeneTree; ENSGT00530000062809; -. DR HOGENOM; HOG000232065; -. DR HOVERGEN; HBG057100; -. DR InParanoid; Q9UQL6; -. DR KO; K11406; -. DR OMA; AANMRTV; -. DR OrthoDB; EOG7RFTH5; -. DR PhylomeDB; Q9UQL6; -. DR TreeFam; TF106174; -. 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 ChiTaRS; HDAC5; human. DR GeneWiki; Histone_deacetylase_5; -. DR GenomeRNAi; 10014; -. DR NextBio; 37831; -. DR PRO; PR:Q9UQL6; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; Q9UQL6; -. DR CleanEx; HS_HDAC5; -. DR ExpressionAtlas; Q9UQL6; baseline and differential. DR Genevisible; Q9UQL6; HS. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000118; C:histone deacetylase complex; TAS:UniProtKB. DR GO; GO:0016604; C:nuclear body; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0001047; F:core promoter binding; IDA:UniProtKB. DR GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC. DR GO; GO:0033558; F:protein deacetylase activity; IMP:UniProtKB. DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB. DR GO; GO:0070491; F:repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001025; F:RNA polymerase III transcription factor binding; IPI:UniProtKB. DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl. DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL. DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; NAS:BHF-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0016568; P:chromatin modification; TAS:UniProtKB. DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; TAS:ProtInc. DR GO; GO:0006342; P:chromatin silencing; TAS:ProtInc. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0016575; P:histone deacetylation; IDA:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0033555; P:multicellular organismal response to stress; IEA:Ensembl. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:0010832; P:negative regulation of myotube differentiation; IMP:BHF-UCL. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl. 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; TAS:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl. DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome. DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl. DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0006476; P:protein deacetylation; IMP:UniProtKB. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:UniProtKB. DR GO; GO:0010830; P:regulation of myotube differentiation; ISS:UniProtKB. DR GO; GO:0043393; P:regulation of protein binding; IMP:BHF-UCL. DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; 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:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.40.800.20; -; 1. DR InterPro; IPR000286; His_deacetylse. DR InterPro; IPR023801; His_deacetylse_dom. DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N. DR InterPro; IPR017320; Histone_deAcase_II_euk. DR InterPro; IPR030703; Histone_deacetylase_5. DR PANTHER; PTHR10625; PTHR10625; 2. DR PANTHER; PTHR10625:SF57; PTHR10625:SF57; 2. DR Pfam; PF12203; HDAC4_Gln; 1. DR Pfam; PF00850; Hist_deacetyl; 1. DR PIRSF; PIRSF037911; HDAC_II_euk; 1. DR PRINTS; PR01270; HDASUPER. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Chromatin regulator; KW Complete proteome; Cytoplasm; Hydrolase; Metal-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc. FT CHAIN 1 1122 Histone deacetylase 5. FT /FTId=PRO_0000114701. FT REGION 684 1028 Histone deacetylase. FT MOTIF 1081 1122 Nuclear export signal. FT COMPBIAS 47 52 Poly-Gly. FT COMPBIAS 85 92 Poly-Gln. FT COMPBIAS 596 599 Poly-Glu. FT COMPBIAS 1099 1104 Poly-Ala. FT ACT_SITE 833 833 {ECO:0000250}. FT METAL 696 696 Zinc. {ECO:0000250}. FT METAL 698 698 Zinc. {ECO:0000250}. FT METAL 704 704 Zinc. {ECO:0000250}. FT METAL 781 781 Zinc. {ECO:0000250}. FT MOD_RES 259 259 Phosphoserine; by AMPK, CaMK1, SIK1 and FT PKD/PRKD1. {ECO:0000269|PubMed:11114197, FT ECO:0000269|PubMed:18184930, FT ECO:0000269|PubMed:18332134}. FT MOD_RES 292 292 Phosphothreonine; by PKC. FT {ECO:0000269|PubMed:20188095}. FT MOD_RES 498 498 Phosphoserine; by AMPK, CaMK1, SIK1 and FT PKD/PRKD1. {ECO:0000269|PubMed:11114197, FT ECO:0000269|PubMed:18184930, FT ECO:0000269|PubMed:18332134}. FT MOD_RES 533 533 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 661 661 Phosphoserine. FT {ECO:0000269|PubMed:11081517}. FT VAR_SEQ 7 7 S -> SA (in isoform 3). FT {ECO:0000303|Ref.6}. FT /FTId=VSP_039180. FT VAR_SEQ 684 768 Missing (in isoform 2). FT {ECO:0000303|PubMed:9628581}. FT /FTId=VSP_002081. FT VARIANT 137 137 R -> Q (in dbSNP:rs438096). FT /FTId=VAR_055903. FT VARIANT 565 565 G -> A (in dbSNP:rs33916560). FT /FTId=VAR_055904. FT MUTAGEN 259 259 S->A: Reduces AMPK- and caMK-dependent FT phosphorylation and the subsequent FT nuclear export. Abolishes nuclear export; FT when associated with A-498. Does not FT affect phosphorylation by PKN1 and PKN2. FT {ECO:0000269|PubMed:11081517, FT ECO:0000269|PubMed:18184930, FT ECO:0000269|PubMed:20188095}. FT MUTAGEN 279 279 S->A: No effect. FT {ECO:0000269|PubMed:11081517}. FT MUTAGEN 291 291 S->A: Does not affect phosphorylation by FT PKC. {ECO:0000269|PubMed:20188095}. FT MUTAGEN 292 292 T->A: Abolishes phosphorylation by PKC. FT {ECO:0000269|PubMed:20188095}. FT MUTAGEN 498 498 S->A: Reduces AMPK- and CaMK-dependent FT phosphorylation and the subsequent FT nuclear export. Abolishes nuclear export; FT when associated with A-259. FT {ECO:0000269|PubMed:11081517, FT ECO:0000269|PubMed:18184930}. FT MUTAGEN 661 661 S->A: No effect. FT {ECO:0000269|PubMed:11081517}. FT MUTAGEN 713 713 S->A: No effect. FT {ECO:0000269|PubMed:11081517}. FT MUTAGEN 1086 1086 V->A: Reduces CaMK-dependent nuclear FT export. {ECO:0000269|PubMed:11509672}. FT MUTAGEN 1092 1092 L->A: Reduces CaMK-dependent nuclear FT export. {ECO:0000269|PubMed:11509672}. FT CONFLICT 37 37 V -> L (in Ref. 6; BX458255). FT {ECO:0000305}. FT CONFLICT 139 139 Q -> R (in Ref. 6; BX458255). FT {ECO:0000305}. FT CONFLICT 147 147 R -> G (in Ref. 6; BX458255). FT {ECO:0000305}. FT CONFLICT 593 593 D -> E (in Ref. 1; AAD29047, 5; AAH51824 FT and 7; AAC18040). {ECO:0000305}. FT CONFLICT 671 671 S -> N (in Ref. 7; AAC18040). FT {ECO:0000305}. FT CONFLICT 684 684 G -> S (in Ref. 7; AAC18040). FT {ECO:0000305}. FT CONFLICT 1026 1026 E -> K (in Ref. 7; AAC18040). FT {ECO:0000305}. FT CONFLICT 1074 1074 E -> G (in Ref. 7; AAC18040). FT {ECO:0000305}. FT CONFLICT 1093 1093 S -> L (in Ref. 7; AAC18040). FT {ECO:0000305}. SQ SEQUENCE 1122 AA; 121978 MW; CF4BE774E3588FEC CRC64; MNSPNESDGM SGREPSLEIL PRTSLHSIPV TVEVKPVLPR AMPSSMGGGG GGSPSPVELR GALVGSVDPT LREQQLQQEL LALKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ QEMLAAKQQQ EMLAAKRQQE LEQQRQREQQ RQEELEKQRL EQQLLILRNK EKSKESAIAS TEVKLRLQEF LLSKSKEPTP GGLNHSLPQH PKCWGAHHAS LDQSSPPQSG PPGTPPSYKL PLPGPYDSRD DFPLRKTASE PNLKVRSRLK QKVAERRSSP LLRRKDGTVI STFKKRAVEI TGAGPGASSV CNSAPGSGPS SPNSSHSTIA ENGFTGSVPN IPTEMLPQHR ALPLDSSPNQ FSLYTSPSLP NISLGLQATV TVTNSHLTAS PKLSTQQEAE RQALQSLRQG GTLTGKFMST SSIPGCLLGV ALEGDGSPHG HASLLQHVLL LEQARQQSTL IAVPLHGQSP LVTGERVATS MRTVGKLPRH RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQLQ LGKILTKTGE LPRQPTTHPE ETEEELTEQQ EVLLGEGALT MPREGSTESE STQEDLEEED EEDDGEEEED CIQVKDEEGE SGAEEGPDLE EPGAGYKKLF SDAQPLQPLQ VYQAPLSLAT VPHQALGRTQ SSPAAPGGMK SPPDQPVKHL FTTGVVYDTF MLKHQCMCGN THVHPEHAGR IQSIWSRLQE TGLLSKCERI RGRKATLDEI QTVHSEYHTL LYGTSPLNRQ KLDSKKLLGP ISQKMYAVLP CGGIGVDSDT VWNEMHSSSA VRMAVGCLLE LAFKVAAGEL KNGFAIIRPP GHHAEESTAM GFCFFNSVAI TAKLLQQKLN VGKVLIVDWD IHHGNGTQQA FYNDPSVLYI SLHRYDNGNF FPGSGAPEEV GGGPGVGYNV NVAWTGGVDP PIGDVEYLTA FRTVVMPIAH EFSPDVVLVS AGFDAVEGHL SPLGGYSVTA RCFGHLTRQL MTLAGGRVVL ALEGGHDLTA ICDASEACVS ALLSVELQPL DEAVLQQKPN INAVATLEKV IEIQSKHWSC VQKFAAGLGR SLREAQAGET EEAETVSAMA LLSVGAEQAQ AAAAREHSPR PAEEPMEQEP AL // ID HDAC9_MOUSE Reviewed; 588 AA. AC Q99N13; Q4QQN7; Q8R4Y6; Q9EPT2; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 2. DT 11-NOV-2015, entry version 132. DE RecName: Full=Histone deacetylase 9; DE Short=HD9; DE EC=3.5.1.98; DE AltName: Full=Histone deacetylase 7B; DE Short=HD7b; DE AltName: Full=Histone deacetylase-related protein; DE AltName: Full=MEF2-interacting transcription repressor MITR; GN Name=Hdac9; Synonyms=Hdac7b, Hdrp, Mitr; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), HOMODIMERIZATION, INTERACTION RP WITH CTBP1; HDAC1; HDAC3; HDAC4 AND HDAC5, AND MUTAGENESIS OF RP 25-ASP-LEU-26. RC STRAIN=NIH Swiss; TISSUE=Embryonic heart; RX PubMed=11022042; DOI=10.1074/jbc.M007364200; RA Zhang C.L., McKinsey T.A., Lu J.R., Olson E.N.; RT "Association of COOH-terminal-binding protein (CtBP) and MEF2- RT interacting transcription repressor (MITR) contributes to RT transcriptional repression of the MEF2 transcription factor."; RL J. Biol. Chem. 276:35-39(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC STRAIN=Swiss Webster / NIH; RA Zhou X., Richon V.M., Rifkind R.A., Marks P.A.; RT "Cloning of the mouse HDRP cDNA."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Retina; 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 FUNCTION, PHOSPHORYLATION AT SER-220 AND SER-450, TISSUE SPECIFICITY, RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION. RX PubMed=11390982; DOI=10.1073/pnas.131198498; RA Zhang C.L., McKinsey T.A., Olson E.N.; RT "The transcriptional corepressor MITR is a signal-responsive inhibitor RT of myogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7354-7359(2001). RN [5] RP PHOSPHORYLATION AT SER-220 AND SER-450, FUNCTION, AND DISRUPTION RP PHENOTYPE. RX PubMed=12202037; DOI=10.1016/S0092-8674(02)00861-9; RA Zhang C.L., McKinsey T.A., Chang S., Antos C.L., Hill J.A., RA Olson E.N.; RT "Class II histone deacetylases act as signal-responsive repressors of RT cardiac hypertrophy."; RL Cell 110:479-488(2002). RN [6] RP PHOSPHORYLATION AT SER-240, AND SUBCELLULAR LOCATION. RX PubMed=15546868; DOI=10.1074/jbc.M411894200; RA Deng X., Ewton D.Z., Mercer S.E., Friedman E.; RT "Mirk/dyrk1B decreases the nuclear accumulation of class II histone RT deacetylases during skeletal muscle differentiation."; RL J. Biol. Chem. 280:4894-4905(2005). RN [7] RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOWN-REGULATION BY RP DENERVATION, INTERACTION WITH HDAC1 AND HDAC3, AND SUBCELLULAR RP LOCATION. RX PubMed=15711539; DOI=10.1038/nn1408; RA Mejat A., Ramond F., Bassel-Duby R., Khochbin S., Olson E.N., RA Schaeffer L.; RT "Histone deacetylase 9 couples neuronal activity to muscle chromatin RT acetylation and gene expression."; RL Nat. Neurosci. 8:313-321(2005). RN [8] RP DOWN-REGULATION BY NEURONAL APOPTOSIS, FUNCTION, AND INTERACTION WITH RP HDAC1 AND MAPK10. RX PubMed=16611996; DOI=10.1128/MCB.26.9.3550-3564.2006; RA Morrison B.E., Majdzadeh N., Zhang X., Lyles A., Bassel-Duby R., RA Olson E.N., D'Mello S.R.; RT "Neuroprotection by histone deacetylase-related protein."; RL Mol. Cell. Biol. 26:3550-3564(2006). RN [9] RP INDUCTION BY MEF2, AND DEVELOPMENTAL STAGE. RX PubMed=17101791; DOI=10.1128/MCB.01415-06; RA Haberland M., Arnold M.A., McAnally J., Phan D., Kim Y., Olson E.N.; RT "Regulation of HDAC9 gene expression by MEF2 establishes a negative- RT feedback loop in the transcriptional circuitry of muscle RT differentiation."; RL Mol. Cell. Biol. 27:518-525(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-552, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 139-158 IN COMPLEX WITH MEF2 RP AND DNA. RX PubMed=15567413; DOI=10.1016/j.jmb.2004.10.033; RA Han A., He J., Wu Y., Liu J.O., Chen L.; RT "Mechanism of recruitment of class II histone deacetylases by myocyte RT enhancer factor-2."; RL J. Mol. Biol. 345:91-102(2005). CC -!- FUNCTION: Devoided of intrinsic deacetylase activity, promotes the CC deacetylation of lysine residues on the N-terminal part of the CC core histones (H2A, H2B, H3 and H4) by recruiting HDAC1 and HDAC3. 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. Represses MEF2-dependent CC transcription, inhibits skeletal myogenesis and may be involved in CC heart development. Protects neurons from apoptosis, both by CC inhibiting JUN phosphorylation by MAPK10 and by repressing JUN CC transcription via HDAC1 recruitment to JUN promoter. CC {ECO:0000269|PubMed:11390982, ECO:0000269|PubMed:12202037, CC ECO:0000269|PubMed:15711539, ECO:0000269|PubMed:16611996}. CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of CC a histone to yield a deacetylated histone. CC -!- SUBUNIT: Homodimer. Interacts with ETV6 (By similarity). Interacts CC with MEF2, HDAC1, HDAC3, HDAC4, HDAC5, CTBP1 and MAPK10. The CC phosphorylated form interacts with 14-3-3. Interacts with FOXP3 in CC the absence of T-cell stimulation (By similarity). CC {ECO:0000250|UniProtKB:Q9UKV0, ECO:0000269|PubMed:11022042, CC ECO:0000269|PubMed:15567413, ECO:0000269|PubMed:15711539, CC ECO:0000269|PubMed:16611996}. CC -!- INTERACTION: CC P60335:Pcbp1; NbExp=6; IntAct=EBI-645361, EBI-309059; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11390982, CC ECO:0000269|PubMed:15546868, ECO:0000269|PubMed:15711539}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q99N13-1; Sequence=Displayed; CC Name=2; Synonyms=Hdrpa; CC IsoId=Q99N13-2; Sequence=VSP_023769; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q99N13-3; Sequence=VSP_029173; CC -!- TISSUE SPECIFICITY: Expressed at high levels in heart, brain and CC spleen. Expressed in skeletal muscle. CC {ECO:0000269|PubMed:11390982, ECO:0000269|PubMed:15711539}. CC -!- DEVELOPMENTAL STAGE: At E10.5, expressed in heart, skeletal muscle CC and neural lineages. At E11.5, expressed in heart, dorsal root CC ganglia and neural tube. At E12.5, expressed in heart, skeletal CC muscle, dorsal root ganglia, neural tube and retina. Strongly up- CC regulated in muscle between E14 and E19 as a result of motor CC innervation. {ECO:0000269|PubMed:11390982, CC ECO:0000269|PubMed:15711539, ECO:0000269|PubMed:17101791}. CC -!- INDUCTION: By MEF2 during muscle differentiation. Down-regulated CC by muscle denervation. Down-regulated by trichostatin A or sodium CC butyrate, and during neuronal apoptosis (at protein level). CC {ECO:0000269|PubMed:17101791}. CC -!- PTM: Sumoylated. {ECO:0000250}. CC -!- PTM: Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3- CC binding, impairs interaction with MEF2, and antagonizes CC antimyogenic activity. Phosphorylated on Ser-240 by DYRK1B; which CC impairs nuclear accumulation. Phosphorylated by the PKC kinases CC PKN1 and PKN2, impairing nuclear import. CC {ECO:0000269|PubMed:11390982, ECO:0000269|PubMed:12202037, CC ECO:0000269|PubMed:15546868}. CC -!- DISRUPTION PHENOTYPE: Mice do not present any abnormality at early CC age but develop cardiac hypertrophy by eight months of age. CC {ECO:0000269|PubMed:12202037}. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2 CC subfamily. {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; AF324492; AAG48332.1; -; mRNA. DR EMBL; AF235053; AAK15027.1; -; mRNA. DR EMBL; AF279371; AAL86358.1; -; mRNA. DR EMBL; BC098187; AAH98187.1; -; mRNA. DR CCDS; CCDS36432.1; -. [Q99N13-1] DR RefSeq; NP_077038.2; NM_024124.3. DR UniGene; Mm.310551; -. DR UniGene; Mm.483009; -. DR PDB; 1TQE; X-ray; 2.70 A; X/Y=139-158. DR PDBsum; 1TQE; -. DR ProteinModelPortal; Q99N13; -. DR SMR; Q99N13; 37-101. DR BioGrid; 219748; 8. DR DIP; DIP-41905N; -. DR IntAct; Q99N13; 5. DR MINT; MINT-146908; -. DR STRING; 10090.ENSMUSP00000106443; -. DR PhosphoSite; Q99N13; -. DR MaxQB; Q99N13; -. DR PaxDb; Q99N13; -. DR PRIDE; Q99N13; -. DR GeneID; 79221; -. DR UCSC; uc007nja.1; mouse. [Q99N13-3] DR UCSC; uc007njb.1; mouse. [Q99N13-2] DR UCSC; uc007njc.2; mouse. [Q99N13-1] DR CTD; 9734; -. DR MGI; MGI:1931221; Hdac9. DR eggNOG; KOG1343; Eukaryota. DR eggNOG; COG0123; LUCA. DR HOGENOM; HOG000232065; -. DR HOVERGEN; HBG057100; -. DR InParanoid; Q99N13; -. DR OrthoDB; EOG7RFTH5; -. DR PhylomeDB; Q99N13; -. DR TreeFam; TF106174; -. DR EvolutionaryTrace; Q99N13; -. DR NextBio; 349885; -. DR PRO; PR:Q99N13; -. DR Proteomes; UP000000589; Unplaced. DR Bgee; Q99N13; -. DR CleanEx; MM_HDAC9; -. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. DR GO; GO:0000118; C:histone deacetylase complex; TAS:UniProtKB. DR GO; GO:0035097; C:histone methyltransferase complex; IDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0005667; C:transcription factor complex; ISO:MGI. DR GO; GO:0004407; F:histone deacetylase activity; TAS:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0033558; F:protein deacetylase activity; ISO:MGI. DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI. DR GO; GO:0070491; F:repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI. DR GO; GO:0008134; F:transcription factor binding; TAS:UniProtKB. DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI. DR GO; GO:0016568; P:chromatin modification; TAS:UniProtKB. DR GO; GO:0007507; P:heart development; IGI:MGI. DR GO; GO:0016575; P:histone deacetylation; ISO:MGI. DR GO; GO:0070932; P:histone H3 deacetylation; ISO:MGI. DR GO; GO:0070933; P:histone H4 deacetylation; ISO:MGI. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; TAS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; TAS:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB. DR GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:MGI. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:MGI. DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; IGI:MGI. DR GO; GO:0051153; P:regulation of striated muscle cell differentiation; IGI:MGI. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR000286; His_deacetylse. DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N. DR PANTHER; PTHR10625; PTHR10625; 1. DR Pfam; PF12203; HDAC4_Gln; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; KW Complete proteome; Hydrolase; Nucleus; Phosphoprotein; KW Reference proteome; Repressor; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1 588 Histone deacetylase 9. FT /FTId=PRO_0000114711. FT REGION 23 27 Interaction with CTBP1. FT REGION 136 154 Interaction with MEF2. FT REGION 175 343 Interaction with MAPK10. FT REGION 218 261 Interaction with ETV6. {ECO:0000250}. FT MOD_RES 22 22 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9UKV0}. FT MOD_RES 220 220 Phosphoserine. FT {ECO:0000269|PubMed:11390982, FT ECO:0000269|PubMed:12202037}. FT MOD_RES 240 240 Phosphoserine; by DYRK1B. FT {ECO:0000269|PubMed:15546868}. FT MOD_RES 450 450 Phosphoserine. FT {ECO:0000269|PubMed:11390982, FT ECO:0000269|PubMed:12202037}. FT MOD_RES 552 552 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT VAR_SEQ 177 178 Missing (in isoform 3). FT {ECO:0000303|PubMed:11022042}. FT /FTId=VSP_029173. FT VAR_SEQ 219 262 Missing (in isoform 2). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_023769. FT MUTAGEN 25 26 DL->AS: Abolishes binding to CTBP1 and FT impairs function in transcription FT repression. FT {ECO:0000269|PubMed:11022042}. FT CONFLICT 120 120 R -> K (in Ref. 2; AAK15027/AAL86358). FT {ECO:0000305}. FT CONFLICT 136 136 R -> K (in Ref. 2; AAK15027/AAL86358). FT {ECO:0000305}. FT CONFLICT 388 388 N -> T (in Ref. 3; AAH98187). FT {ECO:0000305}. FT CONFLICT 523 523 N -> T (in Ref. 1; AAG48332). FT {ECO:0000305}. FT HELIX 143 153 {ECO:0000244|PDB:1TQE}. SQ SEQUENCE 588 AA; 65687 MW; 4ED7FA9F02BD4621 CRC64; MHSMISSVDV KSEVPMGLEP ISPLDLRTDL RMMMPVVDPV VREKQLQQEL LLIQQQQQIQ KQLLIAEFQK QHENLTRQHQ AQLQEHIKEL LAIKQQQELL EKEQKLEQQR QEQEVERHRR EQQLPPLRGK DRGRERAVAS TEVKQKLQEF LLSKSATKDT PTNGKNHSVG RHPKLWYTAA HHTSLDQSSP PLSGTSPSYK YTLPGAQDSK DDFPLRKTAS EPNLKVRSRL KQKVAERRSS PLLRRKDGNL VTSFKKRVFE VAESSVSSSS PGSGPSSPNN GPAGNVTENE ASALPPTPHP EQLVPQQRIL IHEDSMNLLS LYTSPSLPNI TLGLPAVPSP LNASNSLKDK QKCETQMLRQ GVPLPSQYGS SIAASSSHVH VAMEGKPNSS HQALLQHLLL KEQMRQQKLL VAGGVPLHPQ SPLATKERIS PGIRGTHKLP RHRPLNRTQS APLPQSTLAQ LVIQQQHQQF LEKQKQYQQQ IHMNKLLSKS IEQLKQPGSH LEEAEEELQG DQSMEDRAAS KDNSARSDSS ACVEDTLGQV GAVKVKEEPV DSDEDAQIQE MECGEQAAFM QQVIGKDLAP GFVIKVII // ID HDAC7_MOUSE Reviewed; 938 AA. AC Q8C2B3; Q8C2C9; Q8C8X4; Q8CB80; Q8CDA3; Q9JL72; DT 16-MAY-2003, integrated into UniProtKB/Swiss-Prot. DT 16-MAY-2003, sequence version 2. DT 11-NOV-2015, entry version 136. DE RecName: Full=Histone deacetylase 7; DE Short=HD7; DE EC=3.5.1.98; DE AltName: Full=Histone deacetylase 7A; DE Short=HD7a; GN Name=Hdac7; Synonyms=Hdac7a; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH NCOR2 AND SIN3A. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=10640276; RA Kao H.-Y., Downes M., Ordentlich P., Evans R.M.; RT "Isolation of a novel histone deacetylase reveals that class I and RT class II deacetylases promote SMRT-mediated repression."; RL Genes Dev. 14:55-66(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4; 5 AND 6). RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone, Retina, and Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; 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 [4] RP INTERACTION WITH HDAC1; HDAC2; HDAC3; HDAC4; HDAC5; NCOR1; NCOR2; RP SIN3A; SIN3B; RBBP4; RBBP7; MTA1L1; SAP30 AND MBD3, AND MUTAGENESIS OF RP HIS-657; ASP-692; ASP-694 AND HIS-717. RX PubMed=10984530; DOI=10.1073/pnas.97.19.10330; RA Downes M., Ordentlich P., Kao H.-Y., Alvarez J.G.A., Evans R.M.; RT "Identification of a nuclear domain with deacetylase activity."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10330-10335(2000). RN [5] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH MEF2C, AND RP MUTAGENESIS OF HIS-657. RX PubMed=11279209; DOI=10.1074/jbc.M101508200; RA Dressel U., Bailey P.J., Wang S.-C.M., Downes M., Evans R.M., RA Muscat G.E.O.; RT "A dynamic role for HDAC7 in MEF2-mediated muscle differentiation."; RL J. Biol. Chem. 276:17007-17013(2001). RN [6] RP SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH YWHAE; MEF2A; RP MEF2B AND MEF2C, AND MUTAGENESIS OF SER-178; SER-344 AND SER-479. RX PubMed=11585834; DOI=10.1074/jbc.M107631200; RA Kao H.-Y., Verdel A., Tsai C.-C., Simon C., Juguilon H., Khochbin S.; RT "Mechanism for nucleocytoplasmic shuttling of histone deacetylase 7."; RL J. Biol. Chem. 276:47496-47507(2001). RN [7] RP NUCLEAR EXPORT SIGNAL. RX PubMed=11509672; DOI=10.1128/MCB.21.18.6312-6321.2001; RA McKinsey T.A., Zhang C.-L., Olson E.N.; RT "Identification of a signal-responsive nuclear export sequence in RT class II histone deacetylases."; RL Mol. Cell. Biol. 21:6312-6321(2001). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [9] RP PHOSPHORYLATION AT SER-178; SER-344 AND SER-479. RX PubMed=18509061; DOI=10.1073/pnas.0802857105; RA Wang S., Li X., Parra M., Verdin E., Bassel-Duby R., Olson E.N.; RT "Control of endothelial cell proliferation and migration by VEGF RT signaling to histone deacetylase 7."; RL Proc. Natl. Acad. Sci. U.S.A. 105:7738-7743(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=19131326; DOI=10.1074/mcp.M800451-MCP200; RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; RT "Large scale localization of protein phosphorylation by use of RT electron capture dissociation mass spectrometry."; RL Mol. Cell. Proteomics 8:904-912(2009). RN [11] RP INTERACTION WITH FOXP3. RX PubMed=19696312; DOI=10.1126/science.1176077; RA Pan F., Yu H., Dang E.V., Barbi J., Pan X., Grosso J.F., Jinasena D., RA Sharma S.M., McCadden E.M., Getnet D., Drake C.G., Liu J.O., RA Ostrowski M.C., Pardoll D.M.; RT "Eos mediates Foxp3-dependent gene silencing in CD4+ regulatory T RT cells."; RL Science 325:1142-1146(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Heart, Kidney, Lung, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and RT expression."; RL Cell 143:1174-1189(2010). RN [13] RP INTERACTION WITH ZMYND15. RX PubMed=20675388; DOI=10.1074/jbc.M110.116418; RA Yan W., Si Y., Slaymaker S., Li J., Zheng H., Young D.L., Aslanian A., RA Saunders L., Verdin E., Charo I.F.; RT "Zmynd15 encodes a histone deacetylase-dependent transcriptional RT repressor essential for spermiogenesis and male fertility."; RL J. Biol. Chem. 285:31418-31426(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. Involved in muscle CC maturation by repressing transcription of myocyte enhancer factors CC such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it CC shuttles into the cytoplasm, allowing the expression of myocyte CC enhancer factors. Positively regulates the transcriptional CC repressor activity of FOXP3 (By similarity). CC {ECO:0000250|UniProtKB:Q8WUI4, ECO:0000269|PubMed:10640276}. CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of CC a histone to yield a deacetylated histone. CC -!- SUBUNIT: Interacts with KDM5B (By similarity). Interacts with KAT5 CC and EDNRA. Interacts with HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, CC NCOR1, NCOR2, SIN3A, SIN3B, RBBP4, RBBP7, MTA1L1, SAP30 and MBD3. CC Interacts with the 14-3-3 protein YWHAE, MEF2A, MEF2B and MEF2C. CC Interacts with ZMYND15. Interacts with PML (By similarity). CC Interacts with FOXP3. {ECO:0000250|UniProtKB:Q8WUI4, CC ECO:0000269|PubMed:10640276, ECO:0000269|PubMed:10984530, CC ECO:0000269|PubMed:11279209, ECO:0000269|PubMed:11585834, CC ECO:0000269|PubMed:19696312, ECO:0000269|PubMed:20675388}. CC -!- INTERACTION: CC P62259:Ywhae; NbExp=6; IntAct=EBI-643830, EBI-356480; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=In the nucleus, it CC associates with distinct subnuclear dot-like structures. Shuttles CC between the nucleus and the cytoplasm. In muscle cells, it CC shuttles into the cytoplasm during myocyte differentiation. The CC export to cytoplasm depends on the interaction with the 14-3-3 CC protein YWHAE and is due to its phosphorylation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; CC IsoId=Q8C2B3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8C2B3-2; Sequence=VSP_007432, VSP_007434, VSP_007435; CC Name=3; CC IsoId=Q8C2B3-3; Sequence=VSP_007432, VSP_007434; CC Name=4; CC IsoId=Q8C2B3-4; Sequence=VSP_007433, VSP_007434, VSP_007435; CC Name=5; CC IsoId=Q8C2B3-5; Sequence=VSP_007432; CC Name=6; CC IsoId=Q8C2B3-6; Sequence=VSP_007433; CC -!- TISSUE SPECIFICITY: Highly expressed in heart and lung. Expressed CC at intermediate level in muscle. {ECO:0000269|PubMed:10640276, CC ECO:0000269|PubMed:11279209}. CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between CC the nucleus and the cytoplasm. {ECO:0000250}. CC -!- PTM: May be phosphorylated by CaMK1. Phosphorylated by the PKC CC kinases PKN1 and PKN2, impairing nuclear import. Phosphorylation CC at Ser-178 by MARK2, MARK3 and PRKD1 promotes interaction with 14- CC 3-3 proteins and export from the nucleus. Phosphorylation at Ser- CC 178 is a prerequisite for phosphorylation at Ser-204 (By CC similarity). {ECO:0000250}. CC -!- MISCELLANEOUS: Its activity is inhibited by Trichostatin A (TSA), CC a known histone deacetylase inhibitor. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2 CC subfamily. {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; AF207749; AAF31419.1; -; mRNA. DR EMBL; AK030863; BAC27161.1; -; mRNA. DR EMBL; AK036586; BAC29493.1; -; mRNA. DR EMBL; AK044287; BAC31856.1; -; mRNA. DR EMBL; AK088828; BAC40598.1; -; mRNA. DR EMBL; AK088945; BAC40666.1; -; mRNA. DR EMBL; BC057332; AAH57332.1; -; mRNA. DR CCDS; CCDS37188.1; -. [Q8C2B3-1] DR CCDS; CCDS57004.1; -. [Q8C2B3-5] DR CCDS; CCDS57005.1; -. [Q8C2B3-2] DR CCDS; CCDS57006.1; -. [Q8C2B3-3] DR CCDS; CCDS57007.1; -. [Q8C2B3-4] DR RefSeq; NP_001191204.1; NM_001204275.1. [Q8C2B3-3] DR RefSeq; NP_001191205.1; NM_001204276.1. [Q8C2B3-2] DR RefSeq; NP_001191206.1; NM_001204277.1. [Q8C2B3-4] DR RefSeq; NP_001191207.1; NM_001204278.1. [Q8C2B3-5] DR RefSeq; NP_062518.2; NM_019572.3. [Q8C2B3-1] DR RefSeq; XP_006521268.1; XM_006521205.2. DR RefSeq; XP_006521270.1; XM_006521207.2. [Q8C2B3-3] DR RefSeq; XP_006521271.1; XM_006521208.2. [Q8C2B3-3] DR RefSeq; XP_006521272.1; XM_006521209.2. [Q8C2B3-3] DR RefSeq; XP_006521273.1; XM_006521210.1. [Q8C2B3-3] DR RefSeq; XP_011244002.1; XM_011245700.1. [Q8C2B3-5] DR UniGene; Mm.384027; -. DR ProteinModelPortal; Q8C2B3; -. DR SMR; Q8C2B3; 507-887. DR BioGrid; 207862; 5. DR DIP; DIP-42594N; -. DR IntAct; Q8C2B3; 4. DR MINT; MINT-1551781; -. DR STRING; 10090.ENSMUSP00000112110; -. DR PhosphoSite; Q8C2B3; -. DR MaxQB; Q8C2B3; -. DR PaxDb; Q8C2B3; -. DR PRIDE; Q8C2B3; -. DR Ensembl; ENSMUST00000079838; ENSMUSP00000078766; ENSMUSG00000022475. [Q8C2B3-4] DR Ensembl; ENSMUST00000088402; ENSMUSP00000085744; ENSMUSG00000022475. [Q8C2B3-1] DR Ensembl; ENSMUST00000116408; ENSMUSP00000112109; ENSMUSG00000022475. [Q8C2B3-5] DR Ensembl; ENSMUST00000116409; ENSMUSP00000112110; ENSMUSG00000022475. [Q8C2B3-3] DR Ensembl; ENSMUST00000118294; ENSMUSP00000113380; ENSMUSG00000022475. [Q8C2B3-2] DR GeneID; 56233; -. DR KEGG; mmu:56233; -. DR UCSC; uc007xle.2; mouse. [Q8C2B3-1] DR UCSC; uc007xlf.2; mouse. [Q8C2B3-2] DR UCSC; uc007xlg.2; mouse. [Q8C2B3-4] DR UCSC; uc007xlh.2; mouse. [Q8C2B3-3] DR CTD; 51564; -. DR MGI; MGI:1891835; Hdac7. DR eggNOG; KOG1343; Eukaryota. DR eggNOG; COG0123; LUCA. DR GeneTree; ENSGT00530000062809; -. DR HOGENOM; HOG000232065; -. DR HOVERGEN; HBG057100; -. DR InParanoid; Q8C2B3; -. DR KO; K11408; -. DR OMA; AFRIVVM; -. DR OrthoDB; EOG7RFTH5; -. DR PhylomeDB; Q8C2B3; -. DR TreeFam; TF106173; -. DR Reactome; R-MMU-2122947; NOTCH1 Intracellular Domain Regulates Transcription. DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins. DR ChiTaRS; Hdac7; mouse. DR NextBio; 312136; -. DR PMAP-CutDB; Q8C2B3; -. DR PRO; PR:Q8C2B3; -. DR Proteomes; UP000000589; Chromosome 15. DR Bgee; Q8C2B3; -. DR CleanEx; MM_HDAC7; -. DR ExpressionAtlas; Q8C2B3; baseline and differential. DR Genevisible; Q8C2B3; MM. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0000118; C:histone deacetylase complex; TAS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0071889; F:14-3-3 protein binding; ISS:UniProtKB. DR GO; GO:0033613; F:activating transcription factor binding; ISO:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0004407; F:histone deacetylase activity; TAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI. DR GO; GO:0070491; F:repressing transcription factor binding; ISO:MGI. DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI. DR GO; GO:0008134; F:transcription factor binding; TAS:UniProtKB. DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB. DR GO; GO:0007043; P:cell-cell junction assembly; IMP:MGI. DR GO; GO:0016568; P:chromatin modification; TAS:UniProtKB. DR GO; GO:0016575; P:histone deacetylation; TAS:GOC. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISO:MGI. DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISO:MGI. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:MGI. DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; TAS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; TAS:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:MGI. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0001570; P:vasculogenesis; IMP:MGI. DR Gene3D; 3.40.800.20; -; 1. DR InterPro; IPR000286; His_deacetylse. DR InterPro; IPR023801; His_deacetylse_dom. DR PANTHER; PTHR10625; PTHR10625; 2. DR Pfam; PF00850; Hist_deacetyl; 1. DR PRINTS; PR01270; HDASUPER. PE 1: Evidence at protein level; KW Alternative splicing; Chromatin regulator; Complete proteome; KW Cytoplasm; Hydrolase; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Zinc. FT CHAIN 1 938 Histone deacetylase 7. FT /FTId=PRO_0000114706. FT REGION 1 121 Interaction with MEF2C. FT REGION 2 254 Transcription repression 1. FT REGION 72 172 Interaction with MEF2A. FT REGION 241 533 Transcription repression 2. FT REGION 505 852 Histone deacetylase. FT REGION 864 938 Interaction with SIN3A. FT MOTIF 904 938 Nuclear export signal. {ECO:0000250}. FT COMPBIAS 220 226 Poly-Ser. FT ACT_SITE 657 657 {ECO:0000250}. FT METAL 520 520 Zinc. {ECO:0000250}. FT METAL 522 522 Zinc. {ECO:0000250}. FT METAL 528 528 Zinc. {ECO:0000250}. FT METAL 605 605 Zinc. {ECO:0000250}. FT SITE 830 830 Contributes to catalysis. {ECO:0000250}. FT MOD_RES 132 132 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8WUI4}. FT MOD_RES 178 178 Phosphoserine; by MARK2, MARK3 and FT PKD/PRKD1. {ECO:0000305|PubMed:18509061}. FT MOD_RES 204 204 Phosphoserine; by PKD/PRKD2. FT {ECO:0000250}. FT MOD_RES 344 344 Phosphoserine; by PKD/PRKD1. FT {ECO:0000269|PubMed:18509061}. FT MOD_RES 350 350 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8WUI4}. FT MOD_RES 479 479 Phosphoserine; by PKD/PRKD1. FT {ECO:0000269|PubMed:18509061}. FT MOD_RES 582 582 Phosphoserine. FT {ECO:0000244|PubMed:21183079}. FT VAR_SEQ 1 22 Missing (in isoform 2, isoform 3 and FT isoform 5). FT {ECO:0000303|PubMed:16141072}. FT /FTId=VSP_007432. FT VAR_SEQ 138 161 Missing (in isoform 4 and isoform 6). FT {ECO:0000303|PubMed:16141072}. FT /FTId=VSP_007433. FT VAR_SEQ 249 249 E -> EALLGQRLRLQETSLAPFALPTVSLLPAITLGLPAP FT AR (in isoform 2, isoform 3 and isoform FT 4). {ECO:0000303|PubMed:16141072}. FT /FTId=VSP_007434. FT VAR_SEQ 376 382 Missing (in isoform 2 and isoform 4). FT {ECO:0000303|PubMed:16141072}. FT /FTId=VSP_007435. FT MUTAGEN 178 178 S->A: Strong reduction of CaMK1-dependent FT nuclear export. Reduces interaction with FT YWHAE. {ECO:0000269|PubMed:11585834}. FT MUTAGEN 344 344 S->A: Strong reduction of CaMK1-dependent FT nuclear export. Reduces interaction with FT YWHAE. {ECO:0000269|PubMed:11585834}. FT MUTAGEN 479 479 S->A: Strong reduction of CaMK1-dependent FT nuclear export. Reduces interaction with FT YWHAE. {ECO:0000269|PubMed:11585834}. FT MUTAGEN 657 657 H->A: Abolishes deacetylase activity, but FT not the interaction with HDAC2 and HDAC3. FT {ECO:0000269|PubMed:10984530, FT ECO:0000269|PubMed:11279209}. FT MUTAGEN 692 692 D->A: Disrupts the dot-like nuclear FT pattern. {ECO:0000269|PubMed:10984530}. FT MUTAGEN 694 694 D->A: Disrupts the dot-like nuclear FT pattern. Abolishes deacetylase activity, FT but not the interaction with HDAC2 and FT HDAC3. {ECO:0000269|PubMed:10984530}. FT MUTAGEN 717 717 H->A: Abolishes deacetylase activity, but FT not the interaction with HDAC2 and HDAC3. FT {ECO:0000269|PubMed:10984530}. FT CONFLICT 169 169 E -> G (in Ref. 2; BAC27161). FT {ECO:0000305}. FT CONFLICT 183 183 K -> M (in Ref. 2; BAC29493). FT {ECO:0000305}. FT CONFLICT 228 228 P -> T (in Ref. 2; BAC27161). FT {ECO:0000305}. FT CONFLICT 487 487 L -> M (in Ref. 1; AAF31419 and 2; FT BAC40598/BAC40666). {ECO:0000305}. FT CONFLICT 645 645 K -> R (in Ref. 2; BAC29493). FT {ECO:0000305}. FT CONFLICT 661 661 S -> P (in Ref. 2; BAC40598). FT {ECO:0000305}. FT CONFLICT 737 737 G -> A (in Ref. 1; AAF31419). FT {ECO:0000305}. SQ SEQUENCE 938 AA; 101287 MW; 8D4B455CE6F95483 CRC64; MHSPGAGCPA LQPDTPGSQP QPMDLRVGQR PTVEPPPEPA LLTLQHPQRL HRHLFLAGLH QQQRSAEPMR LSMDPPMPEL QGGQQEQELR QLLNKDKSKR SAVASSVVKQ KLAEVILKKQ QAALERTVHP SSPSIPYRTL EPLDTEGAAR SVLSSFLPPV PSLPTEPPEH FPLRKTVSEP NLKLRYKPKK SLERRKNPLL RKESAPPSLR RRPAETLGDS SPSSSSTPAS GCSSPNDSEH GPNPALGSEA DGDRRTHSTL GPRGPVLGNP HAPLFLHHGL EPEAGGTLPS RLQPILLLDP SVSHAPLWTV PGLGPLPFHF AQPLLTTERL SGSGLHRPLN RTRSEPLPPS ATASPLLAPL QPRQDRLKPH VQLIKPAISP PQRPAKPSEK PRLRQIPSAE DLETDGGGVG PMANDGLEHR ESGRGPPEGR GSISLQQHQQ VPPWEQQHLA GRLSQGSPGD SVLIPLAQVG HRPLSRTQSS PAAPVSLLSP EPTCQTQVLN SSETPATGLV YDSVMLKHQC SCGDNSKHPE HAGRIQSIWS RLQERGLRSQ CECLRGRKAS LEELQSVHSE RHVLLYGTNP LSRLKLDNGK LTGLLAQRTF VMLPCGGVGV DTDTIWNELH SSNAARWAAG SVTDLAFKVA SRELKNGFAV VRPPGHHADH STAMGFCFFN SVAIACRQLQ QHGKASKILI VDWDVHHGNG TQQTFYQDPS VLYISLHRHD DGNFFPGSGA VDEVGTGSGE GFNVNVAWAG GLDPPMGDPE YLAAFRIVVM PIAREFAPDL VLVSAGFDAA EGHPAPLGGY HVSAKCFGYM TQQLMNLAGG AVVLALEGGH DLTAICDASE ACVAALLGNK VDPLSEESWK QKPNLSAIRS LEAVVRVHRK YWGCMQRLAS CPDSWLPRVP GADAEVEAVT ALASLSVGIL AEDRPSERLV EEEEPMNL // 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"; 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; 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"; 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; 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 IKZF4_HUMAN Reviewed; 585 AA. AC Q9H2S9; Q96JP3; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 11-SEP-2007, sequence version 2. DT 11-NOV-2015, entry version 115. DE RecName: Full=Zinc finger protein Eos; DE AltName: Full=Ikaros family zinc finger protein 4; GN Name=IKZF4; Synonyms=KIAA1782, ZNFN1A4; 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=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). 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 [MRNA] OF 53-585 (ISOFORM 1), FUNCTION, TISSUE RP SPECIFICITY, AND INTERACTION WITH IKZF1; IKZF2; IKZF3 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 [4] RP FUNCTION. RX PubMed=12015313; DOI=10.1074/jbc.M201694200; RA Koipally J., Georgopoulos K.; RT "A molecular dissection of the repression circuitry of Ikaros."; RL J. Biol. Chem. 277:27697-27705(2002). RN [5] RP FUNCTION, INTERACTION WITH CTBP2, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF 425-PRO--ASP-427. RX PubMed=12444977; DOI=10.1046/j.1432-1033.2002.03313.x; RA Perdomo J., Crossley M.; RT "The Ikaros family protein Eos associates with C-terminal-binding RT protein corepressors."; RL Eur. J. Biochem. 269:5885-5892(2002). RN [6] RP STRUCTURE BY NMR OF 155-216 IN COMPLEX WITH ZINC IONS. RG Northeast structural genomics consortium (NESG); RT "Solution NMR structure of zinc finger protein EOS from Homo sapiens, RT Northeast structural genomics consortium (NESG) target HR7992A."; RL Submitted (SEP-2013) to the PDB data bank. CC -!- FUNCTION: DNA-binding protein that binds to the 5'GGGAATRCC-3' CC Ikaros-binding sequence. Transcriptional repressor. Interacts with CC SPI1 and MITF to repress transcription of the CTSK and ACP5 CC promoters via recruitment of corepressors SIN3A and CTBP2. May be CC involved in the development of central and peripheral nervous CC systems. Essential for the inhibitory function of regulatory T- CC cells (Treg). Mediates FOXP3-mediated gene silencing in regulatory CC T-cells (Treg) via recruitment of corepressor CTBP1 (By CC similarity). {ECO:0000250|UniProtKB:Q8C208, CC ECO:0000269|PubMed:10978333, ECO:0000269|PubMed:12015313, CC ECO:0000269|PubMed:12444977}. CC -!- SUBUNIT: Self-associates. Interacts with other family members; CC IKZF1, IKZF2, IKZF3 and IKZF5. Interacts with CTBP2. Interacts CC with SPI1, MITF, FOXP3 and CTBP1 (By similarity). CC {ECO:0000250|UniProtKB:Q8C208, ECO:0000269|PubMed:12444977}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12444977}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H2S9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H2S9-2; Sequence=VSP_027688; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle, low CC levels of expression in heart, thymus, kidney, liver, and spleen. CC Expressed in the hematopoietic cell lines MOLT-4, NALM-6 and K- CC 562. Highly expressed in THP-1 and M-07e cell lines, which have CC characteristics of myeloid and early megakaryocytic cells CC respectively. {ECO:0000269|PubMed:10978333}. CC -!- DOMAIN: The N-terminal zinc fingers are involved in sequence- CC specific DNA binding and heterotypic associations with other CC family members. CC -!- DOMAIN: C-terminal zinc fingers mediate homodimerization. CC -!- MISCELLANEOUS: 'Eos' means 'rising sun' in Greek. 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 -!- SEQUENCE CAUTION: CC Sequence=AAG39221.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB47411.1; Type=Erroneous initiation; 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; AB058685; BAB47411.1; ALT_INIT; mRNA. DR EMBL; BX647761; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AF230809; AAG39221.1; ALT_INIT; mRNA. DR CCDS; CCDS44917.1; -. [Q9H2S9-1] DR RefSeq; NP_071910.3; NM_022465.3. [Q9H2S9-1] DR RefSeq; XP_011536969.1; XM_011538667.1. [Q9H2S9-2] DR UniGene; Hs.553221; -. DR PDB; 2MA7; NMR; -; A=155-216. DR PDBsum; 2MA7; -. DR DisProt; DP00376; -. DR ProteinModelPortal; Q9H2S9; -. DR SMR; Q9H2S9; 99-137, 154-267, 521-561. DR BioGrid; 122146; 16. DR IntAct; Q9H2S9; 2. DR STRING; 9606.ENSP00000262032; -. DR PhosphoSite; Q9H2S9; -. DR BioMuta; IKZF4; -. DR DMDM; 158564025; -. DR MaxQB; Q9H2S9; -. DR PaxDb; Q9H2S9; -. DR PRIDE; Q9H2S9; -. DR DNASU; 64375; -. DR Ensembl; ENST00000262032; ENSP00000262032; ENSG00000123411. [Q9H2S9-1] DR Ensembl; ENST00000431367; ENSP00000412101; ENSG00000123411. [Q9H2S9-1] DR Ensembl; ENST00000547167; ENSP00000448419; ENSG00000123411. [Q9H2S9-1] DR GeneID; 64375; -. DR KEGG; hsa:64375; -. DR UCSC; uc001sjb.1; human. [Q9H2S9-1] DR UCSC; uc001sje.1; human. [Q9H2S9-2] DR CTD; 64375; -. DR GeneCards; IKZF4; -. DR HGNC; HGNC:13179; IKZF4. DR HPA; HPA049016; -. DR MIM; 606239; gene. DR neXtProt; NX_Q9H2S9; -. DR PharmGKB; PA162391948; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00550000074392; -. DR HOGENOM; HOG000049114; -. DR HOVERGEN; HBG004752; -. DR InParanoid; Q9H2S9; -. DR KO; K09220; -. DR OMA; QPSSDKM; -. DR OrthoDB; EOG79GT61; -. DR PhylomeDB; Q9H2S9; -. DR TreeFam; TF331189; -. DR GeneWiki; IKZF4; -. DR GenomeRNAi; 64375; -. DR NextBio; 66301; -. DR PRO; PR:Q9H2S9; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; Q9H2S9; -. DR CleanEx; HS_IKZF4; -. DR ExpressionAtlas; Q9H2S9; baseline and differential. DR Genevisible; Q9H2S9; HS. DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; TAS: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; TAS:UniProtKB. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IBA:GO_Central. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; TAS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. 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 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 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW DNA-binding; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 585 Zinc finger protein Eos. FT /FTId=PRO_0000299468. FT ZN_FING 159 181 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 187 209 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 215 237 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 248 271 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 530 552 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 558 582 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 281 585 Interaction with FOXP3. FT {ECO:0000250|UniProtKB:Q8C208}. FT MOTIF 425 429 CTBP-binding motif PEDLA. FT MOD_RES 105 105 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9UKS7}. FT MOD_RES 335 335 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q9UKS7}. FT VAR_SEQ 1 61 MHTPPALPRRFQGGGRVRTPGSHRQGKDNLERDPSGGCVPD FT FLPQAQDSNHFIMESLFCES -> MDSRYLQLQLYLPSCSL FT LQG (in isoform 2). FT {ECO:0000303|PubMed:11347906}. FT /FTId=VSP_027688. FT MUTAGEN 425 427 PED->AAA: No effect on CTBP2 interaction. FT {ECO:0000269|PubMed:12444977}. FT CONFLICT 145 145 E -> K (in Ref. 3; AAG39221). FT {ECO:0000305}. FT CONFLICT 310 310 P -> A (in Ref. 3; AAG39221). FT {ECO:0000305}. FT CONFLICT 361 361 A -> G (in Ref. 3; AAG39221). FT {ECO:0000305}. FT CONFLICT 390 390 N -> H (in Ref. 3; AAG39221). FT {ECO:0000305}. FT CONFLICT 524 524 G -> S (in Ref. 3; AAG39221). FT {ECO:0000305}. FT HELIX 173 181 {ECO:0000244|PDB:2MA7}. FT STRAND 187 189 {ECO:0000244|PDB:2MA7}. FT TURN 190 193 {ECO:0000244|PDB:2MA7}. FT STRAND 194 197 {ECO:0000244|PDB:2MA7}. FT HELIX 199 205 {ECO:0000244|PDB:2MA7}. FT TURN 206 209 {ECO:0000244|PDB:2MA7}. SQ SEQUENCE 585 AA; 64106 MW; 42AE169A3E2E14D3 CRC64; MHTPPALPRR FQGGGRVRTP GSHRQGKDNL ERDPSGGCVP DFLPQAQDSN HFIMESLFCE SSGDSSLEKE FLGAPVGPSV STPNSQHSSP SRSLSANSIK VEMYSDEESS RLLGPDERLL EKDDSVIVED SLSEPLGYCD GSGPEPHSPG GIRLPNGKLK CDVCGMVCIG PNVLMVHKRS HTGERPFHCN QCGASFTQKG NLLRHIKLHS GEKPFKCPFC NYACRRRDAL TGHLRTHSVS SPTVGKPYKC NYCGRSYKQQ STLEEHKERC HNYLQSLSTE AQALAGQPGD EIRDLEMVPD SMLHSSSERP TFIDRLANSL TKRKRSTPQK FVGEKQMRFS LSDLPYDVNS GGYEKDVELV AHHSLEPGFG SSLAFVGAEH LRPLRLPPTN CISELTPVIS SVYTQMQPLP GRLELPGSRE AGEGPEDLAD GGPLLYRPRG PLTDPGASPS NGCQDSTDTE SNHEDRVAGV VSLPQGPPPQ PPPTIVVGRH SPAYAKEDPK PQEGLLRGTP GPSKEVLRVV GESGEPVKAF KCEHCRILFL DHVMFTIHMG CHGFRDPFEC NICGYHSQDR YEFSSHIVRG EHKVG // ID KLF3_HUMAN Reviewed; 345 AA. AC P57682; Q6PIR1; Q86TN0; Q9P2X6; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 1. DT 11-NOV-2015, entry version 140. DE RecName: Full=Krueppel-like factor 3; DE AltName: Full=Basic krueppel-like factor; DE AltName: Full=CACCC-box-binding protein BKLF; DE AltName: Full=TEF-2; GN Name=KLF3; Synonyms=BKLF; 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). RA Matsumoto N., Yoshida T., Terada M.; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=12812068; RA Wang M.J., Qu X.H., Wang L.S., Zhai Y., Wu S.L., He F.C.; RT "cDNA cloning, subcellular localization and tissue expression of a new RT human Kruppel-like transcription factor: human basic Kruppel-like RT factor (hBKLF)."; RL Yi Chuan Xue Bao 30:1-9(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Hippocampus; 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-250, 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 [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92 AND SER-101, 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-92 AND SER-111, 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 [7] 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 [8] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-198, 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: Binds to the CACCC box of erythroid cell-expressed CC genes. May play a role in hematopoiesis (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Monomer. {ECO:0000250}. CC -!- INTERACTION: CC Q92997:DVL3; NbExp=3; IntAct=EBI-8472267, EBI-739789; CC A2ABF9:EHMT2; NbExp=3; IntAct=EBI-8472267, EBI-10174566; CC Q13643:FHL3; NbExp=4; IntAct=EBI-8472267, EBI-741101; CC Q68G74:LHX8; NbExp=3; IntAct=EBI-8472267, EBI-8474075; CC Q12933:TRAF2; NbExp=3; IntAct=EBI-8472267, EBI-355744; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P57682-1; Sequence=Displayed; CC Name=2; CC IsoId=P57682-2; Sequence=VSP_014532; CC Note=May be due to intron retention. No experimental CC confirmation available.; CC -!- PTM: Sumoylated with SUMO1. Sumoylation is enhanced by PIAS1, CC PIAS2alpha and PIAS2beta, and PIAS4, but not by Pc2. Enhances CC transcriptional repression, but has no effect on DNA binding. CC Sumoylation on Lys-198 is the major site (By similarity). CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 3 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; AB024523; BAA92271.1; -; mRNA. DR EMBL; AF285837; AAK27329.1; -; mRNA. DR EMBL; BC030662; AAH30662.1; -; mRNA. DR EMBL; BC051687; AAH51687.1; -; mRNA. DR CCDS; CCDS3444.1; -. [P57682-1] DR RefSeq; NP_057615.3; NM_016531.5. [P57682-1] DR UniGene; Hs.298658; -. DR ProteinModelPortal; P57682; -. DR SMR; P57682; 251-345. DR BioGrid; 119426; 9. DR IntAct; P57682; 8. DR MINT; MINT-4786517; -. DR STRING; 9606.ENSP00000261438; -. DR PhosphoSite; P57682; -. DR BioMuta; KLF3; -. DR DMDM; 12644533; -. DR MaxQB; P57682; -. DR PaxDb; P57682; -. DR PRIDE; P57682; -. DR DNASU; 51274; -. DR Ensembl; ENST00000261438; ENSP00000261438; ENSG00000109787. [P57682-1] DR Ensembl; ENST00000514033; ENSP00000421252; ENSG00000109787. [P57682-2] DR GeneID; 51274; -. DR KEGG; hsa:51274; -. DR UCSC; uc003gtg.2; human. [P57682-1] DR CTD; 51274; -. DR GeneCards; KLF3; -. DR HGNC; HGNC:16516; KLF3. DR HPA; HPA049512; -. DR MIM; 609392; gene. DR neXtProt; NX_P57682; -. DR PharmGKB; PA30137; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00760000118998; -. DR HOGENOM; HOG000232138; -. DR HOVERGEN; HBG003941; -. DR InParanoid; P57682; -. DR KO; K15605; -. DR OMA; MKKYSPP; -. DR OrthoDB; EOG747PJ4; -. DR PhylomeDB; P57682; -. DR TreeFam; TF350556; -. DR ChiTaRS; KLF3; human. DR GeneWiki; KLF3; -. DR GenomeRNAi; 51274; -. DR NextBio; 54481; -. DR PRO; PR:P57682; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; P57682; -. DR CleanEx; HS_KLF3; -. DR ExpressionAtlas; P57682; baseline and differential. DR Genevisible; P57682; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; NAS:ProtInc. DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl. DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 3. 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; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Complete proteome; DNA-binding; KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 345 Krueppel-like factor 3. FT /FTId=PRO_0000047165. FT ZN_FING 260 284 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 290 314 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 320 342 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 1 74 Repressor domain. FT MOTIF 61 65 CTBP-binding motif. FT COMPBIAS 1 251 Pro-rich. FT MOD_RES 92 92 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 101 101 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 108 108 Phosphoserine. FT {ECO:0000250|UniProtKB:Q60980}. FT MOD_RES 111 111 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 216 216 Phosphoserine. FT {ECO:0000250|UniProtKB:Q60980}. FT MOD_RES 224 224 Phosphoserine. FT {ECO:0000250|UniProtKB:Q60980}. FT MOD_RES 250 250 Phosphoserine. FT {ECO:0000244|PubMed:17081983}. FT CROSSLNK 10 10 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT {ECO:0000250}. FT CROSSLNK 198 198 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 233 345 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_014532. FT VARIANT 207 207 R -> S (in dbSNP:rs17616226). FT /FTId=VAR_052715. FT CONFLICT 85 85 P -> R (in Ref. 3; AAH51687). FT {ECO:0000305}. FT CONFLICT 116 116 P -> H (in Ref. 3; AAH51687). FT {ECO:0000305}. FT CONFLICT 305 305 D -> G (in Ref. 3; AAH30662). FT {ECO:0000305}. SQ SEQUENCE 345 AA; 38829 MW; A490D642AB8F1FDC CRC64; MLMFDPVPVK QEAMDPVSVS YPSNYMESMK PNKYGVIYST PLPEKFFQTP EGLSHGIQME PVDLTVNKRS SPPSAGNSPS SLKFPSSHRR ASPGLSMPSS SPPIKKYSPP SPGVQPFGVP LSMPPVMAAA LSRHGIRSPG ILPVIQPVVV QPVPFMYTSH LQQPLMVSLS EEMENSSSSM QVPVIESYEK PISQKKIKIE PGIEPQRTDY YPEEMSPPLM NSVSPPQALL QENHPSVIVQ PGKRPLPVES PDTQRKRRIH RCDYDGCNKV YTKSSHLKAH RRTHTGEKPY KCTWEGCTWK FARSDELTRH FRKHTGIKPF QCPDCDRSFS RSDHLALHRK RHMLV // ID KLF8_HUMAN Reviewed; 359 AA. AC O95600; B4DJN3; E7EQQ8; L0R3U8; L0R4U2; Q2M246; Q59GV5; Q5HYQ5; AC Q5JXP7; Q6MZJ7; Q9UGC4; DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2001, sequence version 2. DT 11-NOV-2015, entry version 131. DE RecName: Full=Krueppel-like factor 8; DE AltName: Full=Basic krueppel-like factor 3; DE AltName: Full=Zinc finger protein 741; GN Name=KLF8; Synonyms=BKLF3, ZNF741; 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). RA Gorski J.L., MacDonald M., Vananthwerp M., Burright E.N., Bialecki M.; RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), AND ALTERNATIVE RP SPLICING. RX PubMed=23134681; DOI=10.1096/fj.12-220319; RA Camacho-Vanegas O., Till J., Miranda-Lorenzo I., Ozturk B., RA Camacho S.C., Martignetti J.A.; RT "Shaking the family tree: Identification of novel and biologically RT active alternatively spliced isoforms across the KLF family of RT transcription factors."; RL FASEB J. 27:432-436(2013). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [8] RP FUNCTION, SUBUNIT, AND TISSUE SPECIFICITY. RX PubMed=10756197; DOI=10.1093/nar/28.9.1955; RA van Vliet J., Turner J., Crossley M.; RT "Human Kruppel-like factor 8: a CACCC-box binding protein that RT associates with CtBP and represses transcription."; RL Nucleic Acids Res. 28:1955-1962(2000). RN [9] RP FUNCTION. RX PubMed=12820964; DOI=10.1016/S1097-2765(03)00179-5; RA Zhao J., Bian Z.C., Yee K., Chen B.P., Chien S., Guan J.L.; RT "Identification of transcription factor KLF8 as a downstream target of RT focal adhesion kinase in its regulation of cyclin D1 and cell cycle RT progression."; RL Mol. Cell 11:1503-1515(2003). RN [10] RP SUMOYLATION AT LYS-67, INTERACTION WITH PIAS1; PIAS2 AND PIAS4, RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-67 AND LYS-217. RX PubMed=16617055; DOI=10.1074/jbc.M513135200; RA Wei H., Wang X., Gan B., Urvalek A.M., Melkoumian Z.K., Guan J.-L., RA Zhao J.; RT "Sumoylation delimits KLF8 transcriptional activity associated with RT the cell cycle regulation."; RL J. Biol. Chem. 281:16664-16671(2006). CC -!- FUNCTION: Transcriptional repressor and activator. Binds to CACCC- CC boxes promoter elements. Also binds the GT-box of cyclin D1 CC promoter and mediates cell cycle progression at G(1) phase as a CC downstream target of focal adhesion kinase (FAK). CC {ECO:0000269|PubMed:10756197, ECO:0000269|PubMed:12820964, CC ECO:0000269|PubMed:16617055}. CC -!- SUBUNIT: Interacts with corepressor CtBP2. Interacts with PIAS1, CC PIAS2, AND PIAS4; the interaction with each ligase sumoylates CC KLF8. {ECO:0000269|PubMed:10756197, ECO:0000269|PubMed:16617055}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16617055}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O95600-1; Sequence=Displayed; CC Name=2; CC IsoId=O95600-3; Sequence=VSP_045460; CC Name=3; CC IsoId=O95600-4; Sequence=VSP_047480, VSP_045460; CC Name=4; CC IsoId=O95600-5; Sequence=VSP_047481; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10756197}. CC -!- PTM: Sumoylation at Lys-67 represses transcriptional activity and CC reduces cell cycle progression into the G(1) phase. Has no effect CC on subcellular location. {ECO:0000269|PubMed:16617055}. CC -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 3 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; U28282; AAC99849.1; -; mRNA. DR EMBL; HF546207; CCO02793.1; -; mRNA. DR EMBL; HF546208; CCO02794.1; -; mRNA. DR EMBL; HF546209; CCO02795.1; -; mRNA. DR EMBL; AK296156; BAG58895.1; -; mRNA. DR EMBL; AB209004; BAD92241.1; ALT_SEQ; mRNA. DR EMBL; BX641066; CAE46033.1; ALT_SEQ; mRNA. DR EMBL; BX322609; CAI41397.1; -; Genomic_DNA. DR EMBL; AL050309; CAI41397.1; JOINED; Genomic_DNA. DR EMBL; AL050309; CAI42343.1; -; Genomic_DNA. DR EMBL; BX322609; CAI42343.1; JOINED; Genomic_DNA. DR EMBL; BC105130; AAI05131.1; -; mRNA. DR EMBL; BC112109; AAI12110.1; -; mRNA. DR CCDS; CCDS14373.1; -. [O95600-1] DR CCDS; CCDS55428.1; -. [O95600-3] DR RefSeq; NP_001152768.1; NM_001159296.1. [O95600-3] DR RefSeq; NP_009181.2; NM_007250.4. [O95600-1] DR RefSeq; XP_005262034.1; XM_005261977.1. [O95600-1] DR RefSeq; XP_005262035.1; XM_005261978.2. [O95600-1] DR RefSeq; XP_005262036.1; XM_005261979.2. [O95600-1] DR RefSeq; XP_006724638.1; XM_006724575.2. [O95600-3] DR RefSeq; XP_011529062.1; XM_011530760.1. [O95600-4] DR UniGene; Hs.646614; -. DR ProteinModelPortal; O95600; -. DR SMR; O95600; 274-356. DR BioGrid; 116435; 8. DR IntAct; O95600; 1. DR MINT; MINT-7969747; -. DR STRING; 9606.ENSP00000417303; -. DR PhosphoSite; O95600; -. DR BioMuta; KLF8; -. DR PaxDb; O95600; -. DR PRIDE; O95600; -. DR DNASU; 11279; -. DR Ensembl; ENST00000374928; ENSP00000364063; ENSG00000102349. [O95600-3] DR Ensembl; ENST00000468660; ENSP00000417303; ENSG00000102349. [O95600-1] DR GeneID; 11279; -. DR KEGG; hsa:11279; -. DR UCSC; uc004dur.3; human. [O95600-1] DR UCSC; uc011mop.2; human. DR CTD; 11279; -. DR GeneCards; KLF8; -. DR HGNC; HGNC:6351; KLF8. DR MIM; 300286; gene. DR neXtProt; NX_O95600; -. DR PharmGKB; PA30141; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00760000118998; -. DR HOVERGEN; HBG003941; -. DR InParanoid; O95600; -. DR KO; K09205; -. DR OMA; SMLQAPV; -. DR OrthoDB; EOG7Z69CW; -. DR PhylomeDB; O95600; -. DR TreeFam; TF350556; -. DR GeneWiki; KLF8; -. DR GenomeRNAi; 11279; -. DR NextBio; 42937; -. DR PRO; PR:O95600; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; O95600; -. DR CleanEx; HS_KLF8; -. DR ExpressionAtlas; O95600; baseline and differential. DR Genevisible; O95600; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 3. 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; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; DNA-binding; Isopeptide bond; KW Metal-binding; Nucleus; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 359 Krueppel-like factor 8. FT /FTId=PRO_0000047176. FT ZN_FING 274 298 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 304 328 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 334 356 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT CROSSLNK 67 67 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 1 27 MVDMDKLINNLEVQLNSEGGSMQVFKQ -> MSLPEDGMSS FT GHFRSPQLVTWS (in isoform 3). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047480. FT VAR_SEQ 216 299 Missing (in isoform 4). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047481. FT VAR_SEQ 254 359 PAAMAQMQGEESLDLKRRRIHQCDFAGCSKVYTKSSHLKAH FT RRIHTGEKPYKCTWDGCSWKFARSDELTRHFRKHTGIKPFR FT CTDCNRSFSRSDHLSLHRRRHDTM -> REAL (in FT isoform 2 and isoform 3). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:23134681}. FT /FTId=VSP_045460. FT MUTAGEN 67 67 K->R: Abolishes sumoylation. No change in FT nuclear location. Increases FT transcriptional activity and cell cycle FT progression. Abolishes sumoylation; when FT associated with R-217. FT {ECO:0000269|PubMed:16617055}. FT MUTAGEN 217 217 K->R: No change in sumoylation. Abolishes FT sumoylation; when associated with R-67. FT {ECO:0000269|PubMed:16617055}. FT CONFLICT 167 167 S -> I (in Ref. 3; BAG58895). FT {ECO:0000305}. FT CONFLICT 263 263 E -> G (in Ref. 1; AAC99849). FT {ECO:0000305}. SQ SEQUENCE 359 AA; 39314 MW; F8FDCC1FD477C04F CRC64; MVDMDKLINN LEVQLNSEGG SMQVFKQVTA SVRNRDPPEI EYRSNMTSPT LLDANPMENP ALFNDIKIEP PEELLASDFS LPQVEPVDLS FHKPKAPLQP ASMLQAPIRP PKPQSSPQTL VVSTSTSDMS TSANIPTVLT PGSVLTSSQS TGSQQILHVI HTIPSVSLPN KMGGLKTIPV VVQSLPMVYT TLPADGGPAA ITVPLIGGDG KNAGSVKVDP TSMSPLEIPS DSEESTIESG SSALQSLQGL QQEPAAMAQM QGEESLDLKR RRIHQCDFAG CSKVYTKSSH LKAHRRIHTG EKPYKCTWDG CSWKFARSDE LTRHFRKHTG IKPFRCTDCN RSFSRSDHLS LHRRRHDTM // ID KNIR_DROME Reviewed; 429 AA. AC P10734; Q540X6; Q9VPC6; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 11-NOV-2015, entry version 149. DE RecName: Full=Zygotic gap protein knirps; DE AltName: Full=Nuclear receptor subfamily 0 group A member 1; GN Name=kni; Synonyms=NR0A1; ORFNames=CG4717; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; OC Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Oregon-R; TISSUE=Salivary gland; RX PubMed=2904128; DOI=10.1038/336489a0; RA Nauber U., Pankratz M.J., Kilnlin A., Seyffert E., Klemm U., RA Jackle H.; RT "Abdominal segmentation of the Drosophila embryo requires a hormone RT receptor-like protein encoded by the gap gene knirps."; RL Nature 336:489-492(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [3] RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Head; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [5] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=8670869; RA Arnosti D.N., Gray S., Barolo S., Zhou J., Levine M.; RT "The gap protein knirps mediates both quenching and direct repression RT in the Drosophila embryo."; RL EMBO J. 15:3659-3666(1996). CC -!- FUNCTION: Transcriptional repressor. Binds to multiple sites in CC the eve stripe 3 enhancer element. Plays an essential role in the CC segmentation process both by refining the expression patterns of CC gap genes and by establishing pair-rules stripes of gene CC expression. {ECO:0000269|PubMed:8670869}. CC -!- INTERACTION: CC O46036:CtBP; NbExp=2; IntAct=EBI-170297, EBI-159330; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00407, ECO:0000269|PubMed:8670869}. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR0 CC subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00407}. 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; X13331; CAA31709.1; -; Genomic_DNA. DR EMBL; AE014296; AAF51629.2; -; Genomic_DNA. DR EMBL; AY118798; AAM50658.1; -; mRNA. DR PIR; S01919; S01919. DR RefSeq; NP_524187.1; NM_079463.3. DR UniGene; Dm.2511; -. DR ProteinModelPortal; P10734; -. DR SMR; P10734; 5-72. DR BioGrid; 65544; 13. DR DIP; DIP-17716N; -. DR IntAct; P10734; 6. DR MINT; MINT-750168; -. DR STRING; 7227.FBpp0077941; -. DR PaxDb; P10734; -. DR PRIDE; P10734; -. DR GeneID; 40287; -. DR CTD; 40287; -. DR FlyBase; FBgn0001320; kni. DR eggNOG; ENOG410IXHB; Eukaryota. DR eggNOG; ENOG4111HXR; LUCA. DR InParanoid; P10734; -. DR OMA; MSKGGSR; -. DR OrthoDB; EOG7KDF9R; -. DR PhylomeDB; P10734; -. DR SignaLink; P10734; -. DR GenomeRNAi; 40287; -. DR NextBio; 817990; -. DR PRO; PR:P10734; -. DR Proteomes; UP000000803; Chromosome 3L. DR Bgee; P10734; -. DR ExpressionAtlas; P10734; differential. DR Genevisible; P10734; DM. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0070491; F:repressing transcription factor binding; IPI:FlyBase. DR GO; GO:0004879; F:RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding; NAS:FlyBase. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:FlyBase. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:FlyBase. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0046845; P:branched duct epithelial cell fate determination, open tracheal system; TAS:FlyBase. DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase. DR GO; GO:0008544; P:epidermis development; IMP:FlyBase. DR GO; GO:0007427; P:epithelial cell migration, open tracheal system; TAS:FlyBase. DR GO; GO:0030522; P:intracellular receptor signaling pathway; NAS:GOC. DR GO; GO:0007517; P:muscle organ development; IMP:FlyBase. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:FlyBase. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:FlyBase. DR GO; GO:0007424; P:open tracheal system development; TAS:FlyBase. DR GO; GO:0007088; P:regulation of mitotic nuclear division; IMP:FlyBase. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:FlyBase. DR GO; GO:0035151; P:regulation of tube size, open tracheal system; TAS:FlyBase. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0035290; P:trunk segmentation; TAS:FlyBase. DR GO; GO:0007354; P:zygotic determination of anterior/posterior axis, embryo; NAS:FlyBase. DR Gene3D; 3.30.50.10; -; 1. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00047; STROIDFINGER. DR SMART; SM00399; ZnF_C4; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. PE 1: Evidence at protein level; KW Complete proteome; Developmental protein; DNA-binding; Metal-binding; KW Nucleus; Receptor; Reference proteome; Repressor; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 429 Zygotic gap protein knirps. FT /FTId=PRO_0000053743. FT DNA_BIND 2 78 Nuclear receptor. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT ZN_FING 5 25 NR C4-type. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT ZN_FING 42 66 NR C4-type. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT COMPBIAS 97 101 Poly-Ala. FT COMPBIAS 137 142 Poly-His. FT COMPBIAS 143 149 Poly-Gln. FT COMPBIAS 200 213 Poly-Ala. FT COMPBIAS 375 382 Poly-Ser. SQ SEQUENCE 429 AA; 45611 MW; 79CEE86A66AB00C7 CRC64; MNQTCKVCGE PAAGFHFGAF TCEGCKSFFG RSYNNISTIS ECKNEGKCII DKKNRTTCKA CRLRKCYNVG MSKGGSRYGR RSNWFKIHCL LQEHEQAAAA AGKAPPLAGG VSVGGAPSAS SPVGSPHTPG FGDMAAHLHH HHQQQQQQQV PRHPHMPLLG YPSYLSDPSA ALPFFSMMGG VPHQSPFQLP PHLLFPGYHA SAAAAAASAA DAAYRQEMYK HRQSVDSVES QNRFSPASQP PVVQPTSSAR QSPIDVCLEE DVHSVHSHQS SASLLHPIAI RATPTTPTSS SPLSFAAKMQ SLSPVSVCSI GGETTSVVPV HPPTVSAQEG PMDLSMKTSR SSVHSFNDSG SEDQEVEVAP RRKFYQLEAE CLTTSSSSSS HSAAHSPNTT TAHAEVKRQK LGGAEATHFG GFAVAHNAAS AMRGIFVCV // 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 ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms 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 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"; 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; 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 SOX6_HUMAN Reviewed; 828 AA. AC P35712; Q86VX7; Q9BXQ3; Q9BXQ4; Q9BXQ5; Q9H0I8; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 11-NOV-2015, entry version 147. DE RecName: Full=Transcription factor SOX-6; GN Name=SOX6; 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 / MRNA] (ISOFORM 3), ALTERNATIVE RP SPLICING, AND TISSUE SPECIFICITY. RC TISSUE=Lymphocyte, and Myoblast; RX PubMed=11255018; DOI=10.1016/S0378-1119(01)00346-8; RA Cohen-Barak O., Hagiwara N., Arlt M.F., Horton J.P., Brilliant M.H.; RT "Cloning, characterization and chromosome mapping of the human SOX6 RT gene."; RL Gene 265:157-164(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.GR1547R; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D., RA Wambutt R., Korn B., Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and RT analysis of 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). 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 NUCLEOTIDE SEQUENCE [MRNA] OF 632-685 (ISOFORMS 1/2/3). RX PubMed=1614875; DOI=10.1093/nar/20.11.2887; RA Denny P., Swift S., Brand N., Dabhade N., Barton P., Ashworth A.; RT "A conserved family of genes related to the testis determining gene, RT SRY."; RL Nucleic Acids Res. 20:2887-2887(1992). RN [7] RP SUMOYLATION AT LYS-404 AND LYS-417, MUTAGENESIS OF LYS-404 AND RP LYS-417, AND SUBCELLULAR LOCATION. RX PubMed=16442531; DOI=10.1016/j.febslet.2006.01.031; RA Fernandez-Lloris R., Osses N., Jaffray E., Shen L.N., Vaughan O.A., RA Girwood D., Bartrons R., Rosa J.L., Hay R.T., Ventura F.; RT "Repression of SOX6 transcriptional activity by SUMO modification."; RL FEBS Lett. 580:1215-1221(2006). RN [8] 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 [9] 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). CC -!- FUNCTION: Transcriptional activator. Binds specifically to the DNA CC sequence 5'-AACAAT-3'. Plays a key role in several developmental CC processes, including neurogenesis and skeleton formation. CC -!- SUBUNIT: Interacts with DAZAP2. {ECO:0000250}. CC -!- INTERACTION: CC O15266:SHOX; NbExp=3; IntAct=EBI-3505706, EBI-3505698; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00267, ECO:0000269|PubMed:16442531}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P35712-1; Sequence=Displayed; CC Name=2; CC IsoId=P35712-2; Sequence=VSP_039693, VSP_039694, VSP_039695; CC Name=3; CC IsoId=P35712-3; Sequence=VSP_039696; CC Name=4; CC IsoId=P35712-4; Sequence=VSP_039694, VSP_039695; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in a wide variety of tissues, most CC abundantly in skeletal muscle. {ECO:0000269|PubMed:11255018}. CC -!- PTM: Sumoylation inhibits the transcriptional activity. CC {ECO:0000269|PubMed:16442531}. CC -!- SIMILARITY: Contains 1 HMG box DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00267}. CC -!- SEQUENCE CAUTION: CC Sequence=BC037866; Type=Frameshift; Positions=505; 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; AF309034; AAK26115.1; -; mRNA. DR EMBL; AF309476; AAK26243.1; -; Genomic_DNA. DR EMBL; AF309471; AAK26243.1; JOINED; Genomic_DNA. DR EMBL; AF309472; AAK26243.1; JOINED; Genomic_DNA. DR EMBL; AF309473; AAK26243.1; JOINED; Genomic_DNA. DR EMBL; AF309474; AAK26243.1; JOINED; Genomic_DNA. DR EMBL; AF309475; AAK26243.1; JOINED; Genomic_DNA. DR EMBL; AF309476; AAK26244.1; -; Genomic_DNA. DR EMBL; AF309471; AAK26244.1; JOINED; Genomic_DNA. DR EMBL; AF309472; AAK26244.1; JOINED; Genomic_DNA. DR EMBL; AF309473; AAK26244.1; JOINED; Genomic_DNA. DR EMBL; AF309474; AAK26244.1; JOINED; Genomic_DNA. DR EMBL; AF309475; AAK26244.1; JOINED; Genomic_DNA. DR EMBL; AL136780; CAB66714.1; -; mRNA. DR EMBL; AC009869; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC013595; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC027016; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC068405; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC103794; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68458.1; -; Genomic_DNA. DR EMBL; BC037866; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC047064; AAH47064.2; -; mRNA. DR EMBL; X65663; CAA46614.1; -; mRNA. DR CCDS; CCDS53604.1; -. [P35712-4] DR CCDS; CCDS53605.1; -. [P35712-2] DR CCDS; CCDS7821.1; -. [P35712-3] DR RefSeq; NP_001139283.1; NM_001145811.1. [P35712-4] DR RefSeq; NP_001139291.1; NM_001145819.1. DR RefSeq; NP_059978.1; NM_017508.2. [P35712-2] DR RefSeq; NP_201583.2; NM_033326.3. [P35712-3] DR UniGene; Hs.368226; -. DR ProteinModelPortal; P35712; -. DR SMR; P35712; 619-688. DR BioGrid; 120714; 11. DR IntAct; P35712; 3. DR MINT; MINT-4719252; -. DR STRING; 9606.ENSP00000324948; -. DR PhosphoSite; P35712; -. DR BioMuta; SOX6; -. DR DMDM; 215274178; -. DR MaxQB; P35712; -. DR PaxDb; P35712; -. DR PRIDE; P35712; -. DR DNASU; 55553; -. DR Ensembl; ENST00000316399; ENSP00000324948; ENSG00000110693. [P35712-3] DR Ensembl; ENST00000396356; ENSP00000379644; ENSG00000110693. [P35712-3] DR Ensembl; ENST00000527619; ENSP00000434455; ENSG00000110693. [P35712-2] DR Ensembl; ENST00000528252; ENSP00000432134; ENSG00000110693. [P35712-4] DR Ensembl; ENST00000528429; ENSP00000433233; ENSG00000110693. [P35712-1] DR GeneID; 55553; -. DR KEGG; hsa:55553; -. DR UCSC; uc001mmd.3; human. [P35712-2] DR UCSC; uc001mme.3; human. [P35712-1] DR UCSC; uc001mmf.3; human. [P35712-4] DR UCSC; uc001mmg.3; human. [P35712-3] DR CTD; 55553; -. DR GeneCards; SOX6; -. DR HGNC; HGNC:16421; SOX6. DR HPA; HPA001923; -. DR HPA; HPA003908; -. DR MIM; 607257; gene. DR neXtProt; NX_P35712; -. DR PharmGKB; PA38137; -. DR eggNOG; KOG0528; Eukaryota. DR eggNOG; ENOG410YZNG; LUCA. DR GeneTree; ENSGT00760000119274; -. DR HOGENOM; HOG000056455; -. DR HOVERGEN; HBG003915; -. DR InParanoid; P35712; -. DR KO; K09269; -. DR OMA; QQRMESE; -. DR OrthoDB; EOG70087H; -. DR PhylomeDB; P35712; -. DR TreeFam; TF320471; -. DR Reactome; R-HSA-3769402; deactivation of the beta-catenin transactivating complex. DR ChiTaRS; SOX6; human. DR GeneWiki; SOX6; -. DR GenomeRNAi; 55553; -. DR NextBio; 60012; -. DR PRO; PR:P35712; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P35712; -. DR CleanEx; HS_SOX6; -. DR ExpressionAtlas; P35712; baseline and differential. DR Genevisible; P35712; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; NAS:UniProtKB. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IEA:Ensembl. DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl. DR GO; GO:0051216; P:cartilage development; IEA:Ensembl. DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:UniProtKB. DR GO; GO:0048821; P:erythrocyte development; IEA:Ensembl. DR GO; GO:0016458; P:gene silencing; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0007517; P:muscle organ development; NAS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0021778; P:oligodendrocyte cell fate specification; IEA:Ensembl. DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:UniProtKB. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IDA:UniProtKB. DR GO; GO:2000741; P:positive regulation of mesenchymal stem cell differentiation; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.30.10; -; 1. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR027153; SOX-6. DR PANTHER; PTHR10270:SF89; PTHR10270:SF89; 3. DR Pfam; PF00505; HMG_box; 1. DR SMART; SM00398; HMG; 1. DR SUPFAM; SSF47095; SSF47095; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Coiled coil; Complete proteome; KW Developmental protein; DNA-binding; Isopeptide bond; Nucleus; KW Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1 828 Transcription factor SOX-6. FT /FTId=PRO_0000048729. FT DNA_BIND 621 689 HMG box. {ECO:0000255|PROSITE- FT ProRule:PRU00267}. FT COILED 184 262 {ECO:0000255}. FT COMPBIAS 219 261 Gln-rich. FT COMPBIAS 280 285 Poly-Ala. FT COMPBIAS 313 317 Poly-Ala. FT MOD_RES 119 119 Phosphothreonine. FT {ECO:0000250|UniProtKB:P40645}. FT MOD_RES 399 399 Phosphoserine. FT {ECO:0000250|UniProtKB:P40645}. FT MOD_RES 401 401 Phosphothreonine. FT {ECO:0000250|UniProtKB:P40645}. FT MOD_RES 439 439 Phosphoserine. FT {ECO:0000250|UniProtKB:P40645}. FT MOD_RES 442 442 Phosphoserine. FT {ECO:0000250|UniProtKB:P40645}. FT CROSSLNK 404 404 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 417 417 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 1 1 M -> MGRM (in isoform 2). FT {ECO:0000303|PubMed:11230166}. FT /FTId=VSP_039693. FT VAR_SEQ 327 367 Missing (in isoform 2 and isoform 4). FT {ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_039694. FT VAR_SEQ 477 477 S -> SLGKWKSQHQEETYE (in isoform 2 and FT isoform 4). {ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_039695. FT VAR_SEQ 578 597 Missing (in isoform 3). FT {ECO:0000303|PubMed:11255018}. FT /FTId=VSP_039696. FT MUTAGEN 404 404 K->R: Partial loss of sumoylation. FT Complete loss of sumoylation; when FT associated with R-417. FT {ECO:0000269|PubMed:16442531}. FT MUTAGEN 417 417 K->R: Partial loss of sumoylation. FT Complete loss of sumoylation; when FT associated with R-404. FT {ECO:0000269|PubMed:16442531}. FT CONFLICT 330 330 V -> A (in Ref. 1; AAK26115). FT {ECO:0000305}. FT CONFLICT 633 633 K -> R (in Ref. 6; CAA46614). FT {ECO:0000305}. SQ SEQUENCE 828 AA; 91921 MW; 38CA781528C839CF CRC64; MSSKQATSPF ACAADGEDAM TQDLTSREKE EGSDQHVASH LPLHPIMHNK PHSEELPTLV STIQQDADWD SVLSSQQRME SENNKLCSLY SFRNTSTSPH KPDEGSRDRE IMTSVTFGTP ERRKGSLADV VDTLKQKKLE EMTRTEQEDS SCMEKLLSKD WKEKMERLNT SELLGEIKGT PESLAEKERQ LSTMITQLIS LREQLLAAHD EQKKLAASQI EKQRQQMDLA RQQQEQIARQ QQQLLQQQHK INLLQQQIQV QGHMPPLMIP IFPHDQRTLA AAAAAQQGFL FPPGITYKPG DNYPVQFIPS TMAAAAASGL SPLQLQKGHV SHPQINQRLK GLSDRFGRNL DTFEHGGGHS YNHKQIEQLY AAQLASMQVS PGAKMPSTPQ PPNTAGTVSP TGIKNEKRGT SPVTQVKDEA AAQPLNLSSR PKTAEPVKSP TSPTQNLFPA SKTSPVNLPN KSSIPSPIGG SLGRGSSLDI LSSLNSPALF GDQDTVMKAI QEARKMREQI QREQQQQQPH GVDGKLSSIN NMGLNSCRNE KERTRFENLG PQLTGKSNED GKLGPGVIDL TRPEDAEGSK AMNGSAAKLQ QYYCWPTGGA TVAEARVYRD ARGRASSEPH IKRPMNAFMV WAKDERRKIL QAFPDMHNSN ISKILGSRWK SMSNQEKQPY YEEQARLSKI HLEKYPNYKY KPRPKRTCIV DGKKLRIGEY KQLMRSRRQE MRQFFTVGQQ PQIPITTGTG VVYPGAITMA TTTPSPQMTS DCSSTSASPE PSLPVIQSTY GMKTDGGSLA GNEMINGEDE MEMYDDYEDD PKSDYSSENE APEAVSAN // ID T7L1A_XENLA Reviewed; 554 AA. AC P70062; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 14-OCT-2015, entry version 96. DE RecName: Full=Transcription factor 7-like 1-A; DE AltName: Full=HMG box transcription factor 3-A; DE Short=TCF-3-A; DE Short=xTcf-3; GN Name=tcf7l1-a; Synonyms=tcf3, tcf3a; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Amphibia; Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; OC Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DNA-BINDING, AND SUBCELLULAR RP LOCATION. RX PubMed=8756721; DOI=10.1016/S0092-8674(00)80112-9; RA Molenaar M., van de Wetering M., Peterson-Maduro J., Godsave S., RA Korinkek V., Roose J., Destree O., Clevers H.; RT "XTcf-3 transcription factor mediates beta-catenin-induced axis RT formation in Xenopus embryos."; RL Cell 86:391-399(1996). RN [2] RP FUNCTION, DNA-BINDING, AND INTERACTION WITH CTNNB1-A. RX PubMed=9308964; DOI=10.1101/gad.11.18.2359; RA Brannon M., Gomperts M., Sumoy L., Moon R.T., Kimelman D.; RT "A beta-catenin/XTcf-3 complex binds to the siamois promoter to RT regulate dorsal axis specification in Xenopus."; RL Genes Dev. 11:2359-2370(1997). RN [3] RP FUNCTION, AND INTERACTION WITH AES AND TLE4-A. RX PubMed=9783587; DOI=10.1038/26989; RA Roose J., Molenaar M., Peterson J., Hurenkamp J., Brantjes H., RA Moerer P., van de Wetering M., Destree O., Clevers H.; RT "The Xenopus Wnt effector XTcf-3 interacts with Groucho-related RT transcriptional repressors."; RL Nature 395:608-612(1998). RN [4] RP FUNCTION, INTERACTION WITH CTBP-B, AND MUTAGENESIS OF 469-PRO-LEU-470 RP AND 545-PRO-LEU-546. RX PubMed=10375506; RA Brannon M., Brown J.D., Bates R., Kimelman D., Moon R.T.; RT "XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus RT development."; RL Development 126:3159-3170(1999). RN [5] RP FUNCTION. RX PubMed=10495268; DOI=10.1016/S0925-4773(99)00136-7; RA McGrew L.L., Takemaru K., Bates R., Moon R.T.; RT "Direct regulation of the Xenopus engrailed-2 promoter by the Wnt RT signaling pathway, and a molecular screen for Wnt-responsive genes, RT confirm a role for Wnt signaling during neural patterning in RT Xenopus."; RL Mech. Dev. 87:21-32(1999). RN [6] RP FUNCTION. RX PubMed=10559484; DOI=10.1016/S0925-4773(99)00210-5; RA Marikawa Y., Elinson R.P.; RT "Relationship of vegetal cortical dorsal factors in the Xenopus egg RT with the Wnt/beta-catenin signaling pathway."; RL Mech. Dev. 89:93-102(1999). RN [7] RP FUNCTION. RX PubMed=11493528; RA Hamilton F.S., Wheeler G.N., Hoppler S.; RT "Difference in XTcf-3 dependency accounts for change in response to RT beta-catenin-mediated Wnt signalling in Xenopus blastula."; RL Development 128:2063-2073(2001). RN [8] RP FUNCTION. RX PubMed=11356018; DOI=10.1006/dbio.2001.0253; RA Darken R.S., Wilson P.A.; RT "Axis induction by wnt signaling: target promoter responsiveness RT regulates competence."; RL Dev. Biol. 234:42-54(2001). RN [9] RP FUNCTION, INTERACTION WITH CSNK1E; CTNNB1-A AND GSK3B, SUBCELLULAR RP LOCATION, AND PHOSPHORYLATION. RX PubMed=11524435; DOI=10.1083/jcb.200102074; RA Lee E., Salic A., Kirschner M.W.; RT "Physiological regulation of beta-catenin stability by Tcf3 and RT CK1epsilon."; RL J. Cell Biol. 154:983-993(2001). RN [10] RP FUNCTION, AND DNA-BINDING. RX PubMed=11238923; DOI=10.1128/MCB.21.5.1866-1873.2001; RA Snider L., Thirlwell H., Miller J.R., Moon R.T., Groudine M., RA Tapscott S.J.; RT "Inhibition of Tcf3 binding by I-mfa domain proteins."; RL Mol. Cell. Biol. 21:1866-1873(2001). RN [11] RP FUNCTION. RX PubMed=12445388; DOI=10.1016/S0960-9822(02)01280-0; RA Roeel G., Hamilton F.S., Gent Y., Bain A.A., Destree O., Hoppler S.; RT "Lef-1 and Tcf-3 transcription factors mediate tissue-specific Wnt RT signaling during Xenopus development."; RL Curr. Biol. 12:1941-1945(2002). RN [12] RP FUNCTION. RX PubMed=12163405; RA Houston D.W., Kofron M., Resnik E., Langland R., Destree O., Wylie C., RA Heasman J.; RT "Repression of organizer genes in dorsal and ventral Xenopus cells RT mediated by maternal XTcf3."; RL Development 129:4015-4025(2002). RN [13] RP FUNCTION. RX PubMed=11934150; RA Rex M., Hilton E., Old R.W.; RT "Multiple interactions between maternally-activated signalling RT pathways control Xenopus nodal-related genes."; RL Int. J. Dev. Biol. 46:217-226(2002). RN [14] RP DNA-BINDING. RX PubMed=12049769; DOI=10.1016/S0925-4773(02)00121-1; RA Yang J., Mei W., Otto A., Xiao L., Tao Q., Geng X., Rupp R.A.W., RA Ding X.; RT "Repression through a distal TCF-3 binding site restricts Xenopus myf- RT 5 expression in gastrula mesoderm."; RL Mech. Dev. 115:79-89(2002). RN [15] RP FUNCTION. RX PubMed=14568102; DOI=10.1016/j.mod.2003.08.004; RA Hilton E., Rex M., Old R.; RT "VegT activation of the early zygotic gene Xnr5 requires lifting of RT Tcf-mediated repression in the Xenopus blastula."; RL Mech. Dev. 120:1127-1138(2003). RN [16] RP FUNCTION, AND INTERACTION WITH DACT1-A. RX PubMed=15329348; DOI=10.1242/dev.01369; RA Hikasa H., Sokol S.Y.; RT "The involvement of Frodo in TCF-dependent signaling and neural tissue RT development."; RL Development 131:4725-4734(2004). RN [17] RP FUNCTION. RX PubMed=15747128; DOI=10.1007/s00427-005-0474-0; RA Tsuji S., Hashimoto C.; RT "Choice of either beta-catenin or Groucho/TLE as a co-factor for Xtcf- RT 3 determines dorsal-ventral cell fate of diencephalon during Xenopus RT development."; RL Dev. Genes Evol. 215:275-284(2005). RN [18] RP FUNCTION. RX PubMed=15923623; DOI=10.1128/MCB.25.12.5061-5072.2005; RA Snider L., Tapscott S.J.; RT "XIC is required for Siamois activity and dorsoanterior development."; RL Mol. Cell. Biol. 25:5061-5072(2005). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-61. RX PubMed=11136974; DOI=10.1016/S0092-8674(00)00192-6; RA Graham T.A., Weaver C., Mao F., Kimelman D., Xu W.; RT "Crystal structure of a beta-catenin/Tcf complex."; RL Cell 103:885-896(2000). CC -!- FUNCTION: Participates in the Wnt signaling pathway. Binds to DNA CC and acts as a repressor in the absence of ctnnb1-A and possibly CC ctnnb1-B, and as an activator in the presence of these proteins. CC Required early in development for the establishment of the dorsal CC body axis in response to maternal Wnt signaling. Also required CC during development of the CNS for the establishment of dorsal- CC ventral patterning in the prospective diencephalon. CC {ECO:0000269|PubMed:10375506, ECO:0000269|PubMed:10495268, CC ECO:0000269|PubMed:10559484, ECO:0000269|PubMed:11238923, CC ECO:0000269|PubMed:11356018, ECO:0000269|PubMed:11493528, CC ECO:0000269|PubMed:11524435, ECO:0000269|PubMed:11934150, CC ECO:0000269|PubMed:12163405, ECO:0000269|PubMed:12445388, CC ECO:0000269|PubMed:14568102, ECO:0000269|PubMed:15329348, CC ECO:0000269|PubMed:15747128, ECO:0000269|PubMed:15923623, CC ECO:0000269|PubMed:8756721, ECO:0000269|PubMed:9308964, CC ECO:0000269|PubMed:9783587}. CC -!- SUBUNIT: Interacts with csnk1e, ctnnb1-A, ctbp-B, dact1-A and CC gsk3b. May interact with ase and tle4-A. CC {ECO:0000269|PubMed:10375506, ECO:0000269|PubMed:11524435, CC ECO:0000269|PubMed:15329348, ECO:0000269|PubMed:9308964, CC ECO:0000269|PubMed:9783587}. CC -!- INTERACTION: CC Q8JJ48:dact1-a; NbExp=3; IntAct=EBI-6259044, EBI-6259065; CC A0SNQ7:tshz3; NbExp=2; IntAct=EBI-6259044, EBI-7373787; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- PTM: Phosphorylated. Phosphorylation by csnk1e promotes binding to CC ctnnb1-A while phosphorylation by gsk3b may reverse this effect. CC {ECO:0000269|PubMed:11524435}. CC -!- SIMILARITY: Belongs to the TCF/LEF family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 HMG box DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00267}. 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; X99308; CAA67686.1; -; mRNA. DR RefSeq; NP_001081483.1; NM_001088014.1. DR UniGene; Xl.1100; -. DR PDB; 1G3J; X-ray; 2.10 A; B/D=1-61. DR PDBsum; 1G3J; -. DR ProteinModelPortal; P70062; -. DR SMR; P70062; 2-52, 323-398. DR IntAct; P70062; 5. DR MINT; MINT-4790980; -. DR GeneID; 397863; -. DR KEGG; xla:397863; -. DR CTD; 397863; -. DR Xenbase; XB-GENE-6252329; tcf7l1. DR HOVERGEN; HBG000419; -. DR KO; K04490; -. DR EvolutionaryTrace; P70062; -. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IC:UniProtKB. DR GO; GO:0005667; C:transcription factor complex; IPI:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:InterPro. 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:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.30.10; -; 1. DR Gene3D; 4.10.900.10; -; 1. DR InterPro; IPR027397; Catenin_binding_dom. DR InterPro; IPR013558; CTNNB1-bd_N. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR024940; TCF/LEF. DR InterPro; IPR028778; Tcf7l1. DR PANTHER; PTHR10373; PTHR10373; 1. DR PANTHER; PTHR10373:SF25; PTHR10373:SF25; 1. DR Pfam; PF08347; CTNNB1_binding; 1. DR Pfam; PF00505; HMG_box; 1. DR SMART; SM00398; HMG; 1. DR SUPFAM; SSF47095; SSF47095; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Cytoplasm; Developmental protein; KW DNA-binding; Nucleus; Phosphoprotein; Repressor; Transcription; KW Transcription regulation; Wnt signaling pathway. FT CHAIN 1 554 Transcription factor 7-like 1-A. FT /FTId=PRO_0000048616. FT DNA_BIND 324 392 HMG box. {ECO:0000255|PROSITE- FT ProRule:PRU00267}. FT REGION 1 61 Interaction with CTNNB1-A. FT REGION 109 312 Interaction with AES and TLE4-A. FT REGION 408 554 Interaction with CTBP-B. FT COMPBIAS 148 291 Pro-rich. FT COMPBIAS 483 528 Ser-rich. FT MUTAGEN 469 470 PL->AS: May abrogate binding to CTBP-B. FT {ECO:0000269|PubMed:10375506}. FT MUTAGEN 545 546 PL->AS: May abrogate binding to CTBP-B. FT {ECO:0000269|PubMed:10375506}. FT HELIX 42 49 {ECO:0000244|PDB:1G3J}. SQ SEQUENCE 554 AA; 60300 MW; 90B24D134AE4EBDD CRC64; MPQLNSGGGD ELGANDELIR FKDEGEQEEK SPGEGSAEGD LADVKSSLVN ESENHSSDSD SEVERRPPPR EAFEKHRDYL TEALRRQQDA AFFKGPPYAG YPFLMIPDLG GHYLPNGALS PSARTYLQMK WPLLDSPSTA GLKDARSPSP AHLSNKVPVV QHPHHMHPLT PLITYSNEHF SPGTPPGHLS PEIDPKTGIP RPPHPSELSP YYPLSPGAVG QIPHPLGWLV PPQGQPMYSI PPGGFRHPYP ALAMNASMSS LVSSRFSPHM VPPPHHSLHT SGIPHPAIVS PIVKQEPSSG NISPNLHTKS NMIVKKEEEK KPHIKKPLNA FMLYMKEMRA KVVAECTLKE SAAINQILGR RWHSLSREEQ AKYYELARKE RQLHSQLYPS WSARDNYGKR KKRKREKQSP EMETHTKTKK MCVQHLPADK SCDSPASSHG SMLDSPATPS AALASPAAPA ATHSEQAQPL SLTTKPEARA QLSLSHSAAF LASKSPSSSS FSGHLSSPVG SPLLSRPIPL TSSILSPSGV FPSALQALPL LQAQPLSLVT KSSD // ID TGIF1_HUMAN Reviewed; 401 AA. AC Q15583; A6NE42; A6NLU7; F8VZB6; Q6ICR0; Q8N5X9; Q9NRS0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 11-NOV-2015, entry version 169. DE RecName: Full=Homeobox protein TGIF1; DE AltName: Full=5'-TG-3'-interacting factor 1; GN Name=TGIF1; Synonyms=TGIF; 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 2). RC TISSUE=Liver; RX PubMed=8537382; DOI=10.1074/jbc.270.52.31178; RA Bertolino E., Reimund B., Wildt-Perinic D., Clerc R.G.; RT "A novel homeobox protein which recognizes a TGT core and functionally RT interferes with a retinoid-responsive motif."; RL J. Biol. Chem. 270:31178-31188(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT SER-292. RC TISSUE=Brain; RX PubMed=10764806; DOI=10.1074/jbc.M908382199; RA Yang Y., Hwang C.K., D'Souza U.M., Lee S.-H., Junn E., Mouradian M.M.; RT "Three-amino acid extension loop homeodomain proteins Meis2 and TGIF RT differentially regulate transcription."; RL J. Biol. Chem. 275:20734-20741(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT RP SER-292. 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 (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-137 (ISOFORM 4). RC TISSUE=Brain, Placenta, and Rhabdomyosarcoma; 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 STRUCTURE BY NMR OF 171-248. RG Northeast structural genomics consortium (NESG); RT "Solution NMR structure of homeobox domain (171-248) of human homeobox RT protein TGIF1, northeast structural genomics consortium target RT hr4411b."; RL Submitted (OCT-2011) to the PDB data bank. RN [9] RP VARIANTS HPE4 CYS-157; ARG-192; ALA-280 AND PHE-291. RX PubMed=10835638; DOI=10.1038/76074; RA Gripp K.W., Wotton D., Edwards M.C., Roessler E., Ades L., RA Meinecke P., Richieri-Costa A., Zackai E.H., Massague J., Muenke M., RA Elledge S.J.; RT "Mutations in TGIF cause holoprosencephaly and link NODAL signalling RT to human neural axis determination."; RL Nat. Genet. 25:205-208(2000). RN [10] RP VARIANT HPE4 LEU-236. RX PubMed=15221788; DOI=10.1002/humu.20056; RA Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., RA Le Duff F., Durou M.-R., Odent S., David V.; RT "Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients RT with features of holoprosencephaly spectrum: mutation review and RT genotype-phenotype correlations."; RL Hum. Mutat. 24:43-51(2004). CC -!- FUNCTION: Binds to a retinoid X receptor (RXR) responsive element CC from the cellular retinol-binding protein II promoter (CRBPII- CC RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha CC transcription activation of the retinoic acid responsive element. CC Active transcriptional corepressor of SMAD2. Links the nodal CC signaling pathway to the bifurcation of the forebrain and the CC establishment of ventral midline structures. May participate in CC the transmission of nuclear signals during development and in the CC adult, as illustrated by the down-modulation of the RXR alpha CC activities. CC -!- SUBUNIT: Interacts with CTBP, SMAD2, SMAD3 and HDAC1. CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-714215, EBI-10171858; CC P56545:CTBP2; NbExp=5; IntAct=EBI-714215, EBI-741533; CC O00214:LGALS8; NbExp=10; IntAct=EBI-714215, EBI-740058; CC Q99750:MDFI; NbExp=4; IntAct=EBI-714215, EBI-724076; CC P29590:PML; NbExp=3; IntAct=EBI-714215, EBI-295890; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q15583-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15583-2; Sequence=VSP_013020, VSP_013021; CC Name=3; CC IsoId=Q15583-3; Sequence=VSP_043108, VSP_043109; CC Name=4; CC IsoId=Q15583-4; Sequence=VSP_046848; CC Note=No experimental confirmation available.; CC -!- DISEASE: Holoprosencephaly 4 (HPE4) [MIM:142946]: A structural CC anomaly of the brain, in which the developing forebrain fails to CC correctly separate into right and left hemispheres. CC Holoprosencephaly is genetically heterogeneous and associated with CC several distinct facies and phenotypic variability. CC {ECO:0000269|PubMed:10835638, ECO:0000269|PubMed:15221788}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the TALE/TGIF homeobox family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. 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; X89750; CAA61897.1; -; mRNA. DR EMBL; AF179900; AAF81643.1; -; mRNA. DR EMBL; CR450333; CAG29329.1; -; mRNA. DR EMBL; AK291112; BAF83801.1; -; mRNA. DR EMBL; AP001025; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471113; EAX01672.1; -; Genomic_DNA. DR EMBL; BC000814; AAH00814.1; -; mRNA. DR EMBL; BC031268; AAH31268.1; -; mRNA. DR EMBL; BE296707; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS11832.1; -. [Q15583-3] DR CCDS; CCDS11833.1; -. [Q15583-2] DR CCDS; CCDS11834.1; -. [Q15583-1] DR CCDS; CCDS11835.1; -. [Q15583-4] DR RefSeq; NP_001265611.1; NM_001278682.1. DR RefSeq; NP_001265613.1; NM_001278684.1. [Q15583-2] DR RefSeq; NP_001265615.1; NM_001278686.1. [Q15583-4] DR RefSeq; NP_003235.1; NM_003244.3. [Q15583-2] DR RefSeq; NP_733796.2; NM_170695.3. [Q15583-1] DR RefSeq; NP_775299.1; NM_173207.2. [Q15583-3] DR RefSeq; NP_775300.1; NM_173208.2. [Q15583-2] DR RefSeq; NP_775301.1; NM_173209.2. [Q15583-4] DR RefSeq; NP_775302.1; NM_173210.2. [Q15583-4] DR RefSeq; NP_775303.1; NM_173211.1. [Q15583-4] DR RefSeq; NP_777480.1; NM_174886.2. [Q15583-4] DR RefSeq; XP_011524037.1; XM_011525735.1. [Q15583-4] DR UniGene; Hs.373550; -. DR PDB; 2LK2; NMR; -; A=171-248. DR PDBsum; 2LK2; -. DR ProteinModelPortal; Q15583; -. DR SMR; Q15583; 171-248. DR BioGrid; 112908; 21. DR IntAct; Q15583; 9. DR MINT; MINT-145985; -. DR STRING; 9606.ENSP00000327959; -. DR PhosphoSite; Q15583; -. DR BioMuta; TGIF1; -. DR DMDM; 215274200; -. DR MaxQB; Q15583; -. DR PaxDb; Q15583; -. DR PRIDE; Q15583; -. DR Ensembl; ENST00000330513; ENSP00000327959; ENSG00000177426. [Q15583-1] DR Ensembl; ENST00000343820; ENSP00000339631; ENSG00000177426. [Q15583-2] DR Ensembl; ENST00000345133; ENSP00000343969; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000400167; ENSP00000383031; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000401449; ENSP00000385206; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000405385; ENSP00000384970; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000407501; ENSP00000384133; ENSG00000177426. [Q15583-2] DR Ensembl; ENST00000472042; ENSP00000449501; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000548489; ENSP00000447747; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000551541; ENSP00000450025; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000618001; ENSP00000483499; ENSG00000177426. [Q15583-3] DR GeneID; 7050; -. DR KEGG; hsa:7050; -. DR UCSC; uc002klu.3; human. [Q15583-1] DR UCSC; uc002klv.3; human. [Q15583-3] DR UCSC; uc002klw.3; human. [Q15583-2] DR CTD; 7050; -. DR GeneCards; TGIF1; -. DR GeneReviews; TGIF1; -. DR H-InvDB; HIX0174209; -. DR HGNC; HGNC:11776; TGIF1. DR HPA; CAB004596; -. DR HPA; HPA062160; -. DR MIM; 142946; phenotype. DR MIM; 602630; gene. DR neXtProt; NX_Q15583; -. DR Orphanet; 93925; Alobar holoprosencephaly. DR Orphanet; 93924; Lobar holoprosencephaly. DR Orphanet; 280200; Microform holoprosencephaly. DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly. DR Orphanet; 220386; Semilobar holoprosencephaly. DR Orphanet; 280195; Septopreoptic holoprosencephaly. DR PharmGKB; PA36489; -. DR eggNOG; KOG0773; Eukaryota. DR eggNOG; ENOG410XPMQ; LUCA. DR GeneTree; ENSGT00550000074260; -. DR HOGENOM; HOG000232039; -. DR HOVERGEN; HBG001143; -. DR InParanoid; Q15583; -. DR KO; K19383; -. DR OMA; IAANNFT; -. DR PhylomeDB; Q15583; -. DR TreeFam; TF318093; -. DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR SignaLink; Q15583; -. DR EvolutionaryTrace; Q15583; -. DR GeneWiki; Homeobox_protein_TGIF1; -. DR GenomeRNAi; 7050; -. DR NextBio; 27551; -. DR PRO; PR:Q15583; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; Q15583; -. DR CleanEx; HS_TGIF1; -. DR ExpressionAtlas; Q15583; baseline and differential. DR Genevisible; Q15583; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0038092; P:nodal signaling pathway; IEA:Ensembl. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0010470; P:regulation of gastrulation; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; TAS:Reactome. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR Gene3D; 1.10.10.60; -; 1. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR008422; Homeobox_KN_domain. DR InterPro; IPR009057; Homeodomain-like. DR Pfam; PF05920; Homeobox_KN; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Disease mutation; DNA-binding; Holoprosencephaly; Homeobox; Nucleus; KW Polymorphism; Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1 401 Homeobox protein TGIF1. FT /FTId=PRO_0000049318. FT DNA_BIND 164 226 Homeobox; TALE-type. FT {ECO:0000255|PROSITE-ProRule:PRU00108}. FT MOTIF 153 157 CTBP-binding motif. FT COMPBIAS 165 168 Poly-Arg. FT VAR_SEQ 1 149 Missing (in isoform 4). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_046848. FT VAR_SEQ 1 129 Missing (in isoform 2). FT {ECO:0000303|PubMed:10764806, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8537382, FT ECO:0000303|Ref.3}. FT /FTId=VSP_013020. FT VAR_SEQ 1 115 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043108. FT VAR_SEQ 116 134 PSQGAQGPAPRRRLLETMK -> MTCSGKSCALARSSLTSS FT Q (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043109. FT VAR_SEQ 130 133 LETM -> MKGK (in isoform 2). FT {ECO:0000303|PubMed:10764806, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8537382, FT ECO:0000303|Ref.3}. FT /FTId=VSP_013021. FT VARIANT 157 157 S -> C (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009961. FT VARIANT 192 192 P -> R (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009962. FT VARIANT 236 236 Q -> L (in HPE4). FT {ECO:0000269|PubMed:15221788}. FT /FTId=VAR_023803. FT VARIANT 280 280 T -> A (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009963. FT VARIANT 289 289 P -> S (in dbSNP:rs11571512). FT /FTId=VAR_047363. FT VARIANT 291 291 S -> F (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009964. FT VARIANT 292 292 P -> L (in dbSNP:rs2229333). FT /FTId=VAR_020151. FT VARIANT 292 292 P -> S (in dbSNP:rs4468717). FT {ECO:0000269|PubMed:10764806, FT ECO:0000269|Ref.3}. FT /FTId=VAR_061268. FT CONFLICT 96 96 P -> Q (in Ref. 7; AAH31268). FT {ECO:0000305}. FT HELIX 173 185 {ECO:0000244|PDB:2LK2}. FT HELIX 188 190 {ECO:0000244|PDB:2LK2}. FT HELIX 194 203 {ECO:0000244|PDB:2LK2}. FT STRAND 204 206 {ECO:0000244|PDB:2LK2}. FT HELIX 208 230 {ECO:0000244|PDB:2LK2}. SQ SEQUENCE 401 AA; 43013 MW; 4D9C76AFB37A29F0 CRC64; MVLAQSRVSA GVGSPHCSGS GGGGSDSFPW PASHPGNPQC SFSTAFLASP RLSRGTLAYL PPAPWSSLAT PSALLGSSCA PPPPPARCPQ PRALSPELGT KAGPRRPHRW ELPRSPSQGA QGPAPRRRLL ETMKGIVAAS GSETEDEDSM DIPLDLSSSA GSGKRRRRGN LPKESVQILR DWLYEHRYNA YPSEQEKALL SQQTHLSTLQ VCNWFINARR RLLPDMLRKD GKDPNQFTIS RRGAKISETS SVESVMGIKN FMPALEETPF HSCTAGPNPT LGRPLSPKPS SPGSVLARPS VICHTTVTAL KDVPFSLCQS VGVGQNTDIQ QIAAKNFTDT SLMYPEDTCK SGPSTNTQSG LFNTPPPTPP DLNQDFSGFQ LLVDVALKRA AEMELQAKLT A // ID TRPS1_HUMAN Reviewed; 1281 AA. AC Q9UHF7; B4E1Z5; Q08AU2; Q9NWE1; Q9UHH6; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 27-MAR-2002, sequence version 2. DT 11-NOV-2015, entry version 140. DE RecName: Full=Zinc finger transcription factor Trps1; DE AltName: Full=Tricho-rhino-phalangeal syndrome type I protein; DE AltName: Full=Zinc finger protein GC79; GN Name=TRPS1; 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 2). RX PubMed=10615131; DOI=10.1038/71717; RA Momeni P., Gloeckner G., Schmidt O., von Holtum D., Albrecht B., RA Gillessen-Kaesbach G., Hennekam R.C.M., Meinecke P., Zabel B., RA Rosenthal A., Horsthemke B., Luedecke H.-J.; RT "Mutations in a new gene, encoding a zinc-finger protein, cause RT tricho-rhino-phalangeal syndrome type I."; RL Nat. Genet. 24:71-74(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Prostate; RX PubMed=10974077; DOI=10.1093/jnci/92.17.1414; RA Chang G.T.G., Steenbeek M., Schippers E., Blok L.J., van Weerden W.M., RA van Alewijk D.C.J.G., Eussen B.H.J., van Steenbrugge G.J., RA Brinkmann A.O.; RT "Characterization of a zinc-finger protein and its association with RT apoptosis in prostate cancer cells."; RL J. Natl. Cancer Inst. 92:1414-1421(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 495-1281 (ISOFORM 1). RC TISSUE=Embryo, and Trachea; 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=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., RA Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 RNF4, AND SUBCELLULAR LOCATION. RX PubMed=12885770; DOI=10.1074/jbc.M306259200; RA Kaiser F.J., Moeroey T., Chang G.T., Horsthemke B., Luedecke H.J.; RT "The RING finger protein RNF4, a co-regulator of transcription, RT interacts with the TRPS1 transcription factor."; RL J. Biol. Chem. 278:38780-38785(2003). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1085, 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 [8] RP SUMOYLATION AT LYS-1192 AND LYS-1201, FUNCTION, AND MUTAGENESIS OF RP LYS-1192 AND LYS-1201. RX PubMed=17391059; DOI=10.1515/BC.2007.051; RA Kaiser F.J., Ludecke H.J., Weger S.; RT "SUMOylation modulates transcriptional repression by TRPS1."; RL Biol. Chem. 388:381-390(2007). 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 INTERACTION WITH GLI3. RX PubMed=19389374; DOI=10.1016/j.ydbio.2009.01.012; RA Wuelling M., Kaiser F.J., Buelens L.A., Braunholz D., Shivdasani R.A., RA Depping R., Vortkamp A.; RT "Trps1, a regulator of chondrocyte proliferation and differentiation, RT interacts with the activator form of Gli3."; RL Dev. Biol. 328:40-53(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-751; SER-1041 AND RP SER-1085, 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 [12] 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 [13] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-766; LYS-850 AND LYS-1201, RP AND 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 [14] RP VARIANTS TRPS3 ASP-894; PRO-901; GLN-908; PRO-908 AND THR-919. RX PubMed=11112658; DOI=10.1086/316926; RA Luedecke H.-J., Schaper J., Meinecke P., Momeni P., Gross S., RA von Holtum D., Hirche H., Abramowicz M.J., Albrecht B., Apacik C., RA Christen H.-J., Claussen U., Devriendt K., Fastnacht E., Forderer A., RA Friedrich U., Goodship T.H.J., Greiwe M., Hamm H., Hennekam R.C.M., RA Hinkel G.K., Hoeltzenbein M., Kayserili H., Majewski F., Mathieu M., RA McLeod R., Midro A.T., Moog U., Nagai T., Niikawa N., Oerstavik K.H., RA Ploechl E., Seitz C., Schmidtke J., Tranebjaerg L., Tsukahara M., RA Wittwer B., Zabel B., Gillessen-Kaesbach G., Horsthemke B.; RT "Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome RT types I and III."; RL Am. J. Hum. Genet. 68:81-91(2001). RN [15] RP VARIANT TRPS3 GLN-908. RX PubMed=11807863; DOI=10.1002/ajmg.10081; RA Kobayashi H., Hino M., Shimodahira M., Iwakura T., Ishihara T., RA Ikekubo K., Ogawa Y., Nakao K., Kurahachi H.; RT "Missense mutation of TRPS1 in a family of tricho-rhino-phalangeal RT syndrome type III."; RL Am. J. Med. Genet. 107:26-29(2002). RN [16] RP VARIANTS TRPS1 CYS-952 AND HIS-952, AND CHARACTERIZATION OF VARIANTS RP TRPS1 CYS-952 AND HIS-952. RX PubMed=14560312; DOI=10.1038/sj.ejhg.5201094; RA Kaiser F.J., Brega P., Raff M.L., Byers P.H., Gallati S., Kay T.T., RA de Almeida S., Horsthemke B., Luedecke H.-J.; RT "Novel missense mutations in the TRPS1 transcription factor define the RT nuclear localization signal."; RL Eur. J. Hum. Genet. 12:121-126(2004). CC -!- FUNCTION: Transcriptional repressor. Binds specifically to GATA CC sequences and represses expression of GATA-regulated genes at CC selected sites and stages in vertebrate development. Regulates CC chondrocyte proliferation and differentiation. Executes multiple CC functions in proliferating chondrocytes, expanding the region of CC distal chondrocytes, activating proliferation in columnar cells CC and supporting the differentiation of columnar into hypertrophic CC chondrocytes. {ECO:0000269|PubMed:12885770, CC ECO:0000269|PubMed:17391059}. CC -!- SUBUNIT: Interacts with RNF4; regulates TRPS1 repressor activity. CC Interacts specifically with the activator form of GLI3 (GLI3A) but CC not with the repressor form (GLI3R). {ECO:0000269|PubMed:12885770, CC ECO:0000269|PubMed:19389374}. CC -!- INTERACTION: CC Q9Q2G4:ORF (xeno); NbExp=3; IntAct=EBI-2556151, EBI-6248094; CC P78317:RNF4; NbExp=2; IntAct=EBI-2556151, EBI-2340927; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12885770}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9UHF7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UHF7-2; Sequence=VSP_037549; CC Name=3; CC IsoId=Q9UHF7-3; Sequence=VSP_037550; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in the adult. Found in CC fetal brain, lung, kidney, liver, spleen and thymus. More highly CC expressed in androgen-dependent than in androgen-independent CC prostate cancer cells. CC -!- PTM: Sumoylated. Sumoylation in the repressor domain inhibits the CC transcription repression activity. Sumoylation on Lys-1201 is the CC major site. Appears to be sumoylated on multiple sites. CC {ECO:0000269|PubMed:17391059}. CC -!- DISEASE: Tricho-rhino-phalangeal syndrome 1 (TRPS1) [MIM:190350]: CC Autosomal dominant disorder characterized by craniofacial and CC skeletal abnormalities. It is allelic with tricho-rhino-phalangeal CC type 3. Typical features include sparse scalp hair, a bulbous tip CC of the nose, protruding ears, a long flat philtrum and a thin CC upper vermilion border. Skeletal defects include cone-shaped CC epiphyses at the phalanges, hip malformations and short stature. CC {ECO:0000269|PubMed:14560312}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Tricho-rhino-phalangeal syndrome 2 (TRPS2) [MIM:150230]: CC A syndrome that combines the clinical features of tricho-rhino- CC phalangeal syndrome type 1 and multiple exostoses type 1. Affected CC individuals manifest multiple dysmorphic facial features including CC large, laterally protruding ears, a bulbous nose, an elongated CC upper lip, as well as sparse scalp hair, winged scapulae, multiple CC cartilaginous exostoses, redundant skin, and mental retardation. CC Note=The gene represented in this entry is involved in disease CC pathogenesis. A chromosomal aberration resulting in the loss of CC functional copies of TRPS1 and EXT1 has been found in TRPS2 CC patients. CC -!- DISEASE: Tricho-rhino-phalangeal syndrome 3 (TRPS3) [MIM:190351]: CC Autosomal dominant disorder characterized by craniofacial and CC skeletal abnormalities. It is allelic with tricho-rhino-phalangeal CC type 1. In TRPS3 a more severe brachydactyly and growth CC retardation are observed. {ECO:0000269|PubMed:11112658, CC ECO:0000269|PubMed:11807863}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Contains 7 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 1 GATA-type zinc finger. CC {ECO:0000255|PROSITE-ProRule:PRU00094}. CC -!- SEQUENCE CAUTION: CC Sequence=AAI25021.1; Type=Erroneous termination; Positions=854; Note=Translated as Gln.; Evidence={ECO:0000305}; CC Sequence=BAA91441.1; Type=Frameshift; Positions=1276; 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; AF183810; AAF23614.1; -; mRNA. DR EMBL; AF264784; AAG21134.1; -; mRNA. DR EMBL; AK000948; BAA91441.1; ALT_FRAME; mRNA. DR EMBL; AK304046; BAG64957.1; -; mRNA. DR EMBL; AF178030; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC125020; AAI25021.1; ALT_SEQ; mRNA. DR CCDS; CCDS6318.2; -. [Q9UHF7-2] DR CCDS; CCDS64957.1; -. [Q9UHF7-3] DR RefSeq; NP_001269831.1; NM_001282902.2. [Q9UHF7-3] DR RefSeq; NP_001269832.1; NM_001282903.2. DR RefSeq; NP_054831.2; NM_014112.4. [Q9UHF7-2] DR RefSeq; XP_005251106.1; XM_005251049.2. [Q9UHF7-1] DR RefSeq; XP_006716688.1; XM_006716625.1. [Q9UHF7-2] DR RefSeq; XP_011515566.1; XM_011517264.1. [Q9UHF7-2] DR RefSeq; XP_011515567.1; XM_011517265.1. [Q9UHF7-2] DR RefSeq; XP_011515568.1; XM_011517266.1. [Q9UHF7-2] DR RefSeq; XP_011515570.1; XM_011517268.1. [Q9UHF7-1] DR UniGene; Hs.657018; -. DR ProteinModelPortal; Q9UHF7; -. DR SMR; Q9UHF7; 893-938. DR BioGrid; 113078; 13. DR IntAct; Q9UHF7; 6. DR MINT; MINT-271027; -. DR STRING; 9606.ENSP00000379065; -. DR PhosphoSite; Q9UHF7; -. DR DMDM; 20140909; -. DR MaxQB; Q9UHF7; -. DR PaxDb; Q9UHF7; -. DR PRIDE; Q9UHF7; -. DR Ensembl; ENST00000220888; ENSP00000220888; ENSG00000104447. [Q9UHF7-1] DR Ensembl; ENST00000395715; ENSP00000379065; ENSG00000104447. [Q9UHF7-2] DR Ensembl; ENST00000520276; ENSP00000428680; ENSG00000104447. [Q9UHF7-3] DR GeneID; 7227; -. DR KEGG; hsa:7227; -. DR UCSC; uc003yny.3; human. [Q9UHF7-2] DR UCSC; uc003ynz.3; human. [Q9UHF7-1] DR UCSC; uc011lhy.2; human. [Q9UHF7-3] DR CTD; 7227; -. DR GeneCards; TRPS1; -. DR HGNC; HGNC:12340; TRPS1. DR MIM; 150230; phenotype. DR MIM; 190350; phenotype. DR MIM; 190351; phenotype. DR MIM; 604386; gene. DR neXtProt; NX_Q9UHF7; -. DR Orphanet; 502; Langer-Giedion syndrome. DR Orphanet; 77258; Trichorhinophalangeal syndrome type 1 and 3. DR PharmGKB; PA37013; -. DR eggNOG; KOG1601; Eukaryota. DR eggNOG; COG5641; LUCA. DR GeneTree; ENSGT00760000119221; -. DR HOGENOM; HOG000146438; -. DR HOVERGEN; HBG067120; -. DR InParanoid; Q9UHF7; -. DR OMA; ENKEHSC; -. DR OrthoDB; EOG72ZCD8; -. DR PhylomeDB; Q9UHF7; -. DR TreeFam; TF350812; -. DR ChiTaRS; TRPS1; human. DR GeneWiki; Tricho-rhino-phalangeal_syndrome_Type_1; -. DR GenomeRNAi; 7227; -. DR NextBio; 28303; -. DR PRO; PR:Q9UHF7; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; Q9UHF7; -. DR CleanEx; HS_TRPS1; -. DR ExpressionAtlas; Q9UHF7; baseline and differential. DR Genevisible; Q9UHF7; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription factor complex; IBA:GO_Central. DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central. DR GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0001085; F:RNA polymerase II transcription factor binding; IBA:GO_Central. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IBA:GO_Central. DR GO; GO:0048468; P:cell development; IBA:GO_Central. DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central. DR GO; GO:0002062; P:chondrocyte differentiation; IEA:Ensembl. DR GO; GO:0048565; P:digestive tract development; IBA:GO_Central. DR GO; GO:0007507; P:heart development; IBA:GO_Central. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0006607; P:NLS-bearing protein import into nucleus; TAS:ProtInc. DR GO; GO:0009887; P:organ morphogenesis; IBA:GO_Central. DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GOC. DR GO; GO:0032330; P:regulation of chondrocyte differentiation; ISS:UniProtKB. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR GO; GO:0009888; P:tissue development; IBA:GO_Central. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IEA:Ensembl. DR Gene3D; 3.30.50.10; -; 1. DR InterPro; IPR028440; Trps1. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR000679; Znf_GATA. DR InterPro; IPR013088; Znf_NHR/GATA. DR PANTHER; PTHR10071:SF176; PTHR10071:SF176; 2. DR Pfam; PF00320; GATA; 1. DR PRINTS; PR00619; GATAZNFINGER. DR SMART; SM00355; ZnF_C2H2; 9. DR SMART; SM00401; ZnF_GATA; 1. DR PROSITE; PS00344; GATA_ZN_FINGER_1; 1. DR PROSITE; PS50114; GATA_ZN_FINGER_2; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Disease mutation; KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 1281 Zinc finger transcription factor Trps1. FT /FTId=PRO_0000083508. FT ZN_FING 222 247 C2H2-type 1; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT ZN_FING 333 358 C2H2-type 2; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT ZN_FING 614 637 C2H2-type 3; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT ZN_FING 666 689 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 692 715 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 896 920 GATA-type. {ECO:0000255|PROSITE- FT ProRule:PRU00094}. FT ZN_FING 1215 1237 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 1243 1267 C2H2-type 7. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 635 819 Mediates interaction with GLI3. FT REGION 985 1184 Mediates interaction with RNF4. FT {ECO:0000250}. FT REGION 1163 1281 Transcriptional repressor domain. FT {ECO:0000250}. FT MOD_RES 127 127 Phosphoserine. FT {ECO:0000250|UniProtKB:Q925H1}. FT MOD_RES 216 216 Phosphoserine. FT {ECO:0000250|UniProtKB:Q925H1}. FT MOD_RES 751 751 Phosphothreonine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 1041 1041 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 1085 1085 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:20068231}. FT CROSSLNK 766 766 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 850 850 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 1192 1192 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 1201 1201 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. FT CROSSLNK 1201 1201 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 1 1 M -> MPYEVNAGYDFTNM (in isoform 2). FT {ECO:0000303|PubMed:10615131}. FT /FTId=VSP_037549. FT VAR_SEQ 1 1 M -> MQSNM (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_037550. FT VARIANT 654 654 S -> L (in dbSNP:rs7002384). FT /FTId=VAR_038197. FT VARIANT 894 894 V -> D (in TRPS3; in heterozygous status FT has a milder effect causing TRPS1). FT {ECO:0000269|PubMed:11112658}. FT /FTId=VAR_012807. FT VARIANT 901 901 T -> P (in TRPS3; severe). FT {ECO:0000269|PubMed:11112658}. FT /FTId=VAR_012808. FT VARIANT 908 908 R -> P (in TRPS3; severe). FT {ECO:0000269|PubMed:11112658}. FT /FTId=VAR_012809. FT VARIANT 908 908 R -> Q (in TRPS3). FT {ECO:0000269|PubMed:11112658, FT ECO:0000269|PubMed:11807863}. FT /FTId=VAR_012810. FT VARIANT 919 919 A -> T (in TRPS3). FT {ECO:0000269|PubMed:11112658}. FT /FTId=VAR_012811. FT VARIANT 952 952 R -> C (in TRPS1; prevents the transport FT into the nucleus and thus reduces the FT nuclear TRPS1 concentration consistent FT with haploinsufficiency). FT {ECO:0000269|PubMed:14560312}. FT /FTId=VAR_038198. FT VARIANT 952 952 R -> H (in TRPS1; prevents the transport FT into the nucleus and thus reduces the FT nuclear TRPS1 concentration consistent FT with haploinsufficiency). FT {ECO:0000269|PubMed:14560312}. FT /FTId=VAR_038199. FT MUTAGEN 1192 1192 K->R: Very little change in sumoylation FT and 30% reduction in repression activity. FT Almost complete loss of sumoylation and FT 70% reduction in repression activity; FT when associated with R-1201. FT {ECO:0000269|PubMed:17391059}. FT MUTAGEN 1201 1201 K->R: Great loss of sumoylation and 30% FT reduction in repression activity. Almost FT complete loss of sumoylation and 70% FT reduction in repression activity; when FT associated with R-1192. FT {ECO:0000269|PubMed:17391059}. FT CONFLICT 115 115 S -> F (in Ref. 1; AAF23614). FT {ECO:0000305}. FT CONFLICT 582 582 T -> A (in Ref. 3; BAG64957). FT {ECO:0000305}. SQ SEQUENCE 1281 AA; 141521 MW; 2157B04F5BEB71CC CRC64; MVRKKNPPLR NVASEGEGQI LEPIGTESKV SGKNKEFSAD QMSENTDQSD AAELNHKEEH SLHVQDPSSS SKKDLKSAVL SEKAGFNYES PSKGGNFPSF PHDEVTDRNM LAFSSPAAGG VCEPLKSPQR AEADDPQDMA CTPSGDSLET KEDQKMSPKA TEETGQAQSG QANCQGLSPV SVASKNPQVP SDGGVRLNKS KTDLLVNDNP DPAPLSPELQ DFKCNICGYG YYGNDPTDLI KHFRKYHLGL HNRTRQDAEL DSKILALHNM VQFSHSKDFQ KVNRSVFSGV LQDINSSRPV LLNGTYDVQV TSGGTFIGIG RKTPDCQGNT KYFRCKFCNF TYMGNSSTEL EQHFLQTHPN KIKASLPSSE VAKPSEKNSN KSIPALQSSD SGDLGKWQDK ITVKAGDDTP VGYSVPIKPL DSSRQNGTEA TSYYWCKFCS FSCESSSSLK LLEHYGKQHG AVQSGGLNPE LNDKLSRGSV INQNDLAKSS EGETMTKTDK SSSGAKKKDF SSKGAEDNMV TSYNCQFCDF RYSKSHGPDV IVVGPLLRHY QQLHNIHKCT IKHCPFCPRG LCSPEKHLGE ITYPFACRKS NCSHCALLLL HLSPGAAGSS RVKHQCHQCS FTTPDVDVLL FHYESVHESQ ASDVKQEANH LQGSDGQQSV KESKEHSCTK CDFITQVEEE ISRHYRRAHS CYKCRQCSFT AADTQSLLEH FNTVHCQEQD ITTANGEEDG HAISTIKEEP KIDFRVYNLL TPDSKMGEPV SESVVKREKL EEKDGLKEKV WTESSSDDLR NVTWRGADIL RGSPSYTQAS LGLLTPVSGT QEQTKTLRDS PNVEAAHLAR PIYGLAVETK GFLQGAPAGG EKSGALPQQY PASGENKSKD ESQSLLRRRR GSGVFCANCL TTKTSLWRKN ANGGYVCNAC GLYQKLHSTP RPLNIIKQNN GEQIIRRRTR KRLNPEALQA EQLNKQQRGS NEEQVNGSPL ERRSEDHLTE SHQREIPLPS LSKYEAQGSL TKSHSAQQPV LVSQTLDIHK RMQPLHIQIK SPQESTGDPG NSSSVSEGKG SSERGSPIEK YMRPAKHPNY SPPGSPIEKY QYPLFGLPFV HNDFQSEADW LRFWSKYKLS VPGNPHYLSH VPGLPNPCQN YVPYPTFNLP PHFSAVGSDN DIPLDLAIKH SRPGPTANGA SKEKTKAPPN VKNEGPLNVV KTEKVDRSTQ DELSTKCVHC GIVFLDEVMY ALHMSCHGDS GPFQCSICQH LCTDKYDFTT HIQRGLHRNN AQVEKNGKPK E // ID TTKB_DROME Reviewed; 643 AA. AC P17789; A4V3Q4; Q32KE0; Q9V9V1; Q9V9V3; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2002, sequence version 2. DT 11-NOV-2015, entry version 157. DE RecName: Full=Protein tramtrack, beta isoform; DE AltName: Full=Repressor protein fushi tarazu; DE AltName: Full=Tramtrack p69; GN Name=ttk; Synonyms=FTZ-F2; ORFNames=CG1856; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; OC Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE. RC TISSUE=Embryo; RX PubMed=2104801; RA Harrison S.D., Travers A.A.; RT "The tramtrack gene encodes a Drosophila finger protein that interacts RT with the ftz transcriptional regulatory region and shows a novel RT embryonic expression pattern."; RL EMBO J. 9:207-216(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE. RC TISSUE=Embryo; RX PubMed=8223261; RA Brown J.L., Wu C.; RT "Repression of Drosophila pair-rule segmentation genes by ectopic RT expression of tramtrack."; RL Development 117:45-58(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=8504931; DOI=10.1101/gad.7.6.1085; RA Xiong W.C., Montell C.; RT "Tramtrack is a transcriptional repressor required for cell fate RT determination in the Drosophila eye."; RL Genes Dev. 7:1085-1096(1993). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [5] RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Embryo; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Embryo; RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., RA Pacleb J.M., Park S., Wan K.H., Yu C., Celniker S.E.; RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP DNA-BINDING. RX PubMed=1640455; DOI=10.1016/0022-2836(92)90952-G; RA Fairall L., Harrison S.D., Travers A.A., Rhodes D.; RT "Sequence-specific DNA binding by a two zinc-finger peptide from the RT Drosophila melanogaster Tramtrack protein."; RL J. Mol. Biol. 226:349-366(1992). RN [9] RP FUNCTION, INTERACTION WITH TRL, AND HOMODIMERIZATION. RX PubMed=12384587; DOI=10.1093/nar/gkf570; RA Pagans S., Ortiz-Lombardia M., Espinas M.L., Bernues J., Azorin F.; RT "The Drosophila transcription factor tramtrack (TTK) interacts with RT Trithorax-like (GAGA) and represses GAGA-mediated activation."; RL Nucleic Acids Res. 30:4406-4413(2002). RN [10] RP FUNCTION, AND INTERACTION WITH PHYL. RX PubMed=17962185; DOI=10.1074/jbc.M707765200; RA Cooper S.E., Murawsky C.M., Lowe N., Travers A.A.; RT "Two modes of degradation of the tramtrack transcription factors by RT Siah homologues."; RL J. Biol. Chem. 283:1076-1083(2008). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 499-561. RX PubMed=8247159; DOI=10.1038/366483a0; RA Fairall L., Schwabe J.W.R., Chapman L., Finch J.T., Rhodes D.; RT "The crystal structure of a two zinc-finger peptide reveals an RT extension to the rules for zinc-finger/DNA recognition."; RL Nature 366:483-487(1993). CC -!- FUNCTION: Binds to a number of sites in the transcriptional CC regulatory region of ftz. Isoform beta is required to repress CC inappropriate segmentation gene transcription and repress genes CC incompatible with development of photoreceptor cell fates. CC Probable repressor of the transcription of the segmentation genes CC ftz, eve, h, odd, run, and en. Inhibits Trl-dependent activation CC of eve. May bind to the region AGGGC/TGG. Degradation of ttk is CC directed by binding of sinah or sina, via the adapter molecule CC phyl which binds to the BTB domain of ttk. A second method of CC degradation exists that is phyl-independent, this is mediated by CC recognition of motifs in the C-terminus of ttk. CC {ECO:0000269|PubMed:12384587, ECO:0000269|PubMed:17962185, CC ECO:0000269|PubMed:2104801, ECO:0000269|PubMed:8223261, CC ECO:0000269|PubMed:8504931}. CC -!- SUBUNIT: Can form homodimers. Interacts with Trl in vivo via the CC BTB domain. Interacts with phyl. {ECO:0000269|PubMed:12384587, CC ECO:0000269|PubMed:17962185}. CC -!- INTERACTION: CC Q0E8J0:MEP-1; NbExp=6; IntAct=EBI-6173284, EBI-91014; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Beta; Synonyms=p69, C, D, F; CC IsoId=P17789-1; Sequence=Displayed; CC Name=Alpha; Synonyms=p88, A, E; CC IsoId=P42282-1; Sequence=External; CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. CC Expressed in preblastoderm embryos, followed by complete decay CC upon formation of the cellular blastoderm when ftz striped CC expression is at its peak. {ECO:0000269|PubMed:2104801, CC ECO:0000269|PubMed:8223261}. CC -!- SIMILARITY: Contains 1 BTB (POZ) domain. {ECO:0000255|PROSITE- CC ProRule:PRU00037}. CC -!- SIMILARITY: Contains 2 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-3 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA28544.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=ABB36443.1; Type=Frameshift; Positions=83, 426; Evidence={ECO:0000305}; CC Sequence=CAA34981.1; Type=Erroneous initiation; 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; X17121; CAA34981.1; ALT_INIT; mRNA. DR EMBL; M62856; AAA28544.1; ALT_INIT; mRNA. DR EMBL; X71627; CAA50634.1; -; mRNA. DR EMBL; AE014297; AAF57181.1; -; Genomic_DNA. DR EMBL; AE014297; AAF57182.3; -; Genomic_DNA. DR EMBL; AE014297; AAN14283.1; -; Genomic_DNA. DR EMBL; AY122169; AAM52681.1; -; mRNA. DR EMBL; BT001723; AAN71478.1; -; mRNA. DR EMBL; BT023939; ABB36443.1; ALT_FRAME; mRNA. DR PIR; S36017; S36017. DR RefSeq; NP_001189330.1; NM_001202401.1. [P17789-1] DR RefSeq; NP_524911.3; NM_080172.4. [P17789-1] DR RefSeq; NP_733446.1; NM_170567.3. [P17789-1] DR RefSeq; NP_733447.1; NM_170568.3. [P17789-1] DR UniGene; Dm.1526; -. DR PDB; 2DRP; X-ray; 2.80 A; A/D=501-563. DR PDBsum; 2DRP; -. DR ProteinModelPortal; P17789; -. DR SMR; P17789; 15-116, 501-562. DR BioGrid; 71315; 56. DR IntAct; P17789; 3. DR STRING; 7227.FBpp0085186; -. DR PaxDb; P17789; -. DR PRIDE; P17789; -. DR GeneID; 48317; -. DR CTD; 7272; -. DR FlyBase; FBgn0003870; ttk. DR eggNOG; ENOG410IFVR; Eukaryota. DR eggNOG; ENOG410XPVE; LUCA. DR OMA; VFSSQEY; -. DR EvolutionaryTrace; P17789; -. DR GenomeRNAi; 48317; -. DR NextBio; 839310; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; P17789; -. DR ExpressionAtlas; P17789; differential. DR Genevisible; P17789; DM. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0005700; C:polytene chromosome; IDA:FlyBase. DR GO; GO:0017053; C:transcriptional repressor complex; IPI:FlyBase. DR GO; GO:0003682; F:chromatin binding; IDA:FlyBase. DR GO; GO:0003677; F:DNA binding; IDA:FlyBase. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0031208; F:POZ domain binding; IDA:FlyBase. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:FlyBase. DR GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:FlyBase. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:FlyBase. DR GO; GO:0007298; P:border follicle cell migration; IMP:FlyBase. DR GO; GO:0048854; P:brain morphogenesis; IMP:FlyBase. DR GO; GO:0035147; P:branch fusion, open tracheal system; IMP:FlyBase. DR GO; GO:0060446; P:branching involved in open tracheal system development; IMP:FlyBase. DR GO; GO:0001709; P:cell fate determination; TAS:FlyBase. DR GO; GO:0040003; P:chitin-based cuticle development; IMP:FlyBase. DR GO; GO:0042675; P:compound eye cone cell differentiation; IMP:FlyBase. DR GO; GO:0048750; P:compound eye corneal lens morphogenesis; IMP:FlyBase. DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase. DR GO; GO:0046843; P:dorsal appendage formation; IMP:FlyBase. DR GO; GO:0035001; P:dorsal trunk growth, open tracheal system; IMP:FlyBase. DR GO; GO:0007476; P:imaginal disc-derived wing morphogenesis; IMP:FlyBase. DR GO; GO:0002121; P:inter-male aggressive behavior; IMP:FlyBase. DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IMP:FlyBase. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:GOC. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:FlyBase. DR GO; GO:0048666; P:neuron development; IMP:FlyBase. DR GO; GO:0030707; P:ovarian follicle cell development; IMP:FlyBase. DR GO; GO:0007422; P:peripheral nervous system development; TAS:FlyBase. DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:FlyBase. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:FlyBase. DR GO; GO:0048053; P:R1/R6 development; IMP:FlyBase. DR GO; GO:0045467; P:R7 cell development; IMP:FlyBase. DR GO; GO:0008360; P:regulation of cell shape; IMP:FlyBase. DR GO; GO:0042682; P:regulation of compound eye cone cell fate specification; IMP:FlyBase. DR GO; GO:0016476; P:regulation of embryonic cell shape; IMP:FlyBase. DR GO; GO:0035151; P:regulation of tube size, open tracheal system; IMP:FlyBase. DR GO; GO:0001964; P:startle response; IMP:FlyBase. DR GO; GO:0007426; P:tracheal outgrowth, open tracheal system; IMP:FlyBase. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 2. DR InterPro; IPR017956; AT_hook_DNA-bd_motif. DR InterPro; IPR000210; BTB/POZ_dom. 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 Pfam; PF00651; BTB; 1. DR SMART; SM00384; AT_hook; 1. DR SMART; SM00225; BTB; 1. DR SMART; SM00355; ZnF_C2H2; 2. DR SUPFAM; SSF54695; SSF54695; 1. DR PROSITE; PS50097; BTB; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; DNA-binding; KW Metal-binding; Nucleus; Reference proteome; Repeat; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 643 Protein tramtrack, beta isoform. FT /FTId=PRO_0000047079. FT DOMAIN 33 98 BTB. {ECO:0000255|PROSITE- FT ProRule:PRU00037}. FT ZN_FING 508 531 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 538 561 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT CONFLICT 255 255 T -> M (in Ref. 2; AAA28544). FT {ECO:0000305}. FT CONFLICT 281 281 H -> Q (in Ref. 2; AAA28544). FT {ECO:0000305}. FT CONFLICT 501 501 T -> I (in Ref. 2; AAA28544). FT {ECO:0000305}. FT STRAND 501 504 {ECO:0000244|PDB:2DRP}. FT STRAND 507 509 {ECO:0000244|PDB:2DRP}. FT TURN 511 513 {ECO:0000244|PDB:2DRP}. FT STRAND 516 519 {ECO:0000244|PDB:2DRP}. FT HELIX 520 530 {ECO:0000244|PDB:2DRP}. FT STRAND 531 534 {ECO:0000244|PDB:2DRP}. FT TURN 541 543 {ECO:0000244|PDB:2DRP}. FT STRAND 546 548 {ECO:0000244|PDB:2DRP}. FT HELIX 550 560 {ECO:0000244|PDB:2DRP}. SQ SEQUENCE 643 AA; 68771 MW; 98DAEA1A5E97DC59 CRC64; MKMASQRFCL RWNNHQSNLL SVFDQLLHAE TFTDVTLAVE GQHLKAHKMV LSACSPYFNT LFVSHPEKHP IVILKDVPYS DMKSLLDFMY RGEVSVDQER LTAFLRVAES LRIKGLTEVN DDKPSPAAAA AGAGATGSES TATTPQLQRI QPYLVPQRNR SQAGGLLASA ANAGNTPTLP VQPSLLSSAL MPKRKRGRPR KLSGSSNGTG NDYDDFDREN MMNDSSDLGN GKMCNESYSG NDDGSDDNQP NAGHTDDLNE SRDSLPSKRS KNSKDHRVVS HHEDNSTSDG NDSDGEGLDT SYMEPQLMLD EYDEPVEFKY NPLTDNSSPT QDHTDGSHLN EQARQQAFLI AAQRKHQVET AAAAAASGIK LNIIGMAAGG AQVKSMVSIP KLTPIGKVNA ASTPLVSPAG SFSTATVKPR VQKRPKLGKQ NGDVKPAVFS SQEYLDIYNS NDGFKLKAAG LSGSTPNLSA GLGTPSVKTK LNLSSNVGEG EAEGSVRDYC TKEGEHTYRC KVCSRVYTHI SNFCRHYVTS HKRNVKVYPC PFCFKEFTRK DNMTAHVKII HKIENPSTAL ATVAAANLAG QPLGVSGAST PPPPDLSGQN SNQSLPATSN ALSTSSSSST SSSSGSLGPL TTSAPPAPAA AAQ // ID ZEB1_HUMAN Reviewed; 1124 AA. AC P37275; B4DJV0; B4DUW9; E9PCM7; F5H4I8; Q12924; Q13800; Q2KJ05; AC Q5T968; Q5VZ84; Q8NB68; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 11-NOV-2015, entry version 164. DE RecName: Full=Zinc finger E-box-binding homeobox 1; DE AltName: Full=NIL-2-A zinc finger protein; DE AltName: Full=Negative regulator of IL2; DE AltName: Full=Transcription factor 8; DE Short=TCF-8; GN Name=ZEB1; Synonyms=AREB6, TCF8; 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). RX PubMed=8138542; RA Watanabe Y., Kawakami K., Hirayama Y., Nagano K.; RT "Transcription factors positively and negatively regulating the Na,K- RT ATPase alpha 1 subunit gene."; RL J. Biochem. 114:849-855(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Bachman N.J., Scarpulla R.C.; RT "A human zinc finger homeodomain protein homologous to the chicken RT delta-crystallin enhancer binding protein, delta EF1."; RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-798 (ISOFORM 5). RC TISSUE=Brain, and 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 [4] 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 [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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 390-1124. RX PubMed=1840704; DOI=10.1126/science.1840704; RA Williams T.M., Moolten D., Burlein J., Romano J., Bhaerman R., RA Godillot A., Mellon M., Rauscher F.J. III, Kant J.A.; RT "Identification of a zinc finger protein that inhibits IL-2 gene RT expression."; RL Science 254:1791-1794(1991). RN [8] RP INVOLVEMENT IN PPCD3. RX PubMed=16252232; DOI=10.1086/497348; RA Krafchak C.M., Pawar H., Moroi S.E., Sugar A., Lichter P.R., RA Mackey D.A., Mian S., Nairus T., Elner V., Schteingart M.T., RA Downs C.A., Kijek T.G., Johnson J.M., Trager E.H., Rozsa F.W., RA Mandal M.N.A., Epstein M.P., Vollrath D., Ayyagari R., Boehnke M., RA Richards J.E.; RT "Mutations in TCF8 cause posterior polymorphous corneal dystrophy and RT ectopic expression of COL4A3 by corneal endothelial cells."; RL Am. J. Hum. Genet. 77:694-708(2005). RN [9] RP SUMOYLATION AT LYS-347 AND LYS-774. 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 [10] RP IDENTIFICATION 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322, 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). RN [12] 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 [13] RP FUNCTION. RX PubMed=19935649; DOI=10.1038/ncb1998; RA Wellner U., Schubert J., Burk U.C., Schmalhofer O., Zhu F., RA Sonntag A., Waldvogel B., Vannier C., Darling D., zur Hausen A., RA Brunton V.G., Morton J., Sansom O., Schuler J., Stemmler M.P., RA Herzberger C., Hopt U., Keck T., Brabletz S., Brabletz T.; RT "The EMT-activator ZEB1 promotes tumorigenicity by repressing RT stemness-inhibiting microRNAs."; RL Nat. Cell Biol. 11:1487-1495(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642; SER-679 AND RP THR-702, 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 FUNCTION. RX PubMed=20175752; DOI=10.1042/BJ20091578; RA Papadopoulou V., Postigo A., Sanchez-Tillo E., Porter A.C., RA Wagner S.D.; RT "ZEB1 and CtBP form a repressive complex at a distal promoter element RT of the BCL6 locus."; RL Biochem. J. 427:541-550(2010). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SMARCA4, AND TISSUE RP SPECIFICITY. RX PubMed=20418909; DOI=10.1038/onc.2010.102; RA Sanchez-Tillo E., Lazaro A., Torrent R., Cuatrecasas M., Vaquero E.C., RA Castells A., Engel P., Postigo A.; RT "ZEB1 represses E-cadherin and induces an EMT by recruiting the RT SWI/SNF chromatin-remodeling protein BRG1."; RL Oncogene 29:3490-3500(2010). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-679, 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 [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 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-493; LYS-504 AND LYS-515, RP AND 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 [20] RP STRUCTURE BY NMR OF 583-642. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the homeobox domain from human NIL-2-A zinc RT finger protein, transcription factor 8."; RL Submitted (APR-2007) to the PDB data bank. RN [21] RP VARIANTS FECD6 THR-78; ALA-649; PRO-810; PRO-840 AND THR-905. RX PubMed=20036349; DOI=10.1016/j.ajhg.2009.12.001; RA Riazuddin S.A., Zaghloul N.A., Al-Saif A., Davey L., Diplas B.H., RA Meadows D.N., Eghrari A.O., Minear M.A., Li Y.J., Klintworth G.K., RA Afshari N., Gregory S.G., Gottsch J.D., Katsanis N.; RT "Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy RT and interact with FCD4 on chromosome 9p."; RL Am. J. Hum. Genet. 86:45-53(2010). RN [22] RP INVOLVEMENT IN FECD6 AND PPCD3, VARIANT FECD6 HIS-640, RP CHARACTERIZATION OF VARIANTS FECD6 THR-78 AND HIS-640, AND VARIANT RP GLU-525. RX PubMed=23599324; DOI=10.1167/iovs.13-11781; RA Lechner J., Dash D.P., Muszynska D., Hosseini M., Segev F., George S., RA Frazer D.G., Moore J.E., Kaye S.B., Young T., Simpson D.A., RA Churchill A.J., Heon E., Willoughby C.E.; RT "Mutational spectrum of the ZEB1 gene in corneal dystrophies supports RT a genotype-phenotype correlation."; RL Invest. Ophthalmol. Vis. Sci. 54:3215-3223(2013). RN [23] RP VARIANTS FECD6 THR-78; ALA-649; SER-696; PRO-810; PRO-840 AND GLY-905, RP CHARACTERIZATION OF VARIANTS FECD6 THR-78; ALA-649; SER-696; PRO-810; RP PRO-840 AND GLY-905, AND SUBCELLULAR LOCATION. RX PubMed=25190660; DOI=10.1167/iovs.14-15247; RA Chung D.W., Frausto R.F., Ann L.B., Jang M.S., Aldave A.J.; RT "Functional impact of ZEB1 mutations associated with posterior RT polymorphous and Fuchs' endothelial corneal dystrophies."; RL Invest. Ophthalmol. Vis. Sci. 55:6159-6166(2014). CC -!- FUNCTION: Acts as a transcriptional repressor. Inhibits CC interleukin-2 (IL-2) gene expression. Enhances or represses the CC promoter activity of the ATP1A1 gene depending on the quantity of CC cDNA and on the cell type. Represses E-cadherin promoter and CC induces an epithelial-mesenchymal transition (EMT) by recruiting CC SMARCA4/BRG1. Represses BCL6 transcription in the presence of the CC corepressor CTBP1. Positively regulates neuronal differentiation. CC Represses RCOR1 transcription activation during neurogenesis. CC Represses transcription by binding to the E box (5'-CANNTG-3'). CC Promotes tumorigenicity by repressing stemness-inhibiting CC microRNAs. {ECO:0000269|PubMed:19935649, CC ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. CC -!- SUBUNIT: Interacts (via N-terminus) with SMARCA4/BRG1. CC {ECO:0000269|PubMed:20418909}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20418909, CC ECO:0000269|PubMed:25190660}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P37275-1; Sequence=Displayed; CC Name=2; CC IsoId=P37275-2; Sequence=VSP_045184; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=P37275-3; Sequence=VSP_047280; CC Name=4; CC IsoId=P37275-4; Sequence=VSP_047281; CC Name=5; CC IsoId=P37275-5; Sequence=VSP_047279, VSP_045184; CC -!- TISSUE SPECIFICITY: Colocalizes with SMARCA4/BRG1 in E-cadherin- CC negative cells from established lines, and stroma of normal colon CC as well as in de-differentiated epithelial cells at the invasion CC front of colorectal carcinomas (at protein level). Expressed in CC heart and skeletal muscle, but not in liver, spleen, or pancreas. CC {ECO:0000269|PubMed:20418909}. CC -!- DISEASE: Corneal dystrophy, posterior polymorphous, 3 (PPCD3) CC [MIM:609141]: A subtype of posterior corneal dystrophy, a disease CC characterized by alterations of Descemet membrane presenting as CC vesicles, opacities or band-like lesions on slit-lamp examination CC and specular microscopy. Affected patient typically are CC asymptomatic. {ECO:0000269|PubMed:16252232, CC ECO:0000269|PubMed:23599324}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Corneal dystrophy, Fuchs endothelial, 6 (FECD6) CC [MIM:613270]: A corneal disease caused by loss of endothelium of CC the central cornea. It is characterized by focal wart-like guttata CC that arise from Descemet membrane and develop in the central CC cornea, epithelial blisters, reduced vision and pain. Descemet CC membrane is thickened by abnormal collagenous deposition. CC {ECO:0000269|PubMed:20036349, ECO:0000269|PubMed:23599324}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 7 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG62481.1; Type=Frameshift; Positions=177; 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; D15050; BAA03646.1; -; mRNA. DR EMBL; U12170; AAA20602.1; -; mRNA. DR EMBL; AK091478; BAC03673.1; -; mRNA. DR EMBL; AK296244; BAG58962.1; -; mRNA. DR EMBL; AK300830; BAG62481.1; ALT_FRAME; mRNA. DR EMBL; AL158080; CAI17320.1; -; Genomic_DNA. DR EMBL; AL117340; CAI17320.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAI17320.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAI17320.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAH74132.1; -; Genomic_DNA. DR EMBL; AL117340; CAH74132.1; JOINED; Genomic_DNA. DR EMBL; AL158080; CAH74132.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAH74132.1; JOINED; Genomic_DNA. DR EMBL; AL117340; CAI12550.1; -; Genomic_DNA. DR EMBL; AL158080; CAI12550.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAI12550.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAI12550.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAI15108.1; -; Genomic_DNA. DR EMBL; AL117340; CAI15108.1; JOINED; Genomic_DNA. DR EMBL; AL158080; CAI15108.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAI15108.1; JOINED; Genomic_DNA. DR EMBL; CH471072; EAW85989.1; -; Genomic_DNA. DR EMBL; BC112392; AAI12393.1; -; mRNA. DR EMBL; M81699; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS44370.1; -. [P37275-5] DR CCDS; CCDS53505.1; -. [P37275-2] DR CCDS; CCDS53506.1; -. [P37275-4] DR CCDS; CCDS53507.1; -. [P37275-3] DR CCDS; CCDS7169.1; -. [P37275-1] DR PIR; JX0293; JX0293. DR RefSeq; NP_001121600.1; NM_001128128.2. [P37275-5] DR RefSeq; NP_001167564.1; NM_001174093.1. [P37275-4] DR RefSeq; NP_001167565.1; NM_001174094.1. DR RefSeq; NP_001167566.1; NM_001174095.1. [P37275-3] DR RefSeq; NP_001167567.1; NM_001174096.1. [P37275-2] DR RefSeq; NP_110378.3; NM_030751.5. [P37275-1] DR UniGene; Hs.124503; -. DR PDB; 2E19; NMR; -; A=586-642. DR PDBsum; 2E19; -. DR ProteinModelPortal; P37275; -. DR SMR; P37275; 583-642. DR BioGrid; 112796; 22. DR IntAct; P37275; 2. DR MINT; MINT-94525; -. DR STRING; 9606.ENSP00000354487; -. DR PhosphoSite; P37275; -. DR BioMuta; ZEB1; -. DR DMDM; 6166575; -. DR MaxQB; P37275; -. DR PaxDb; P37275; -. DR PRIDE; P37275; -. DR Ensembl; ENST00000320985; ENSP00000319248; ENSG00000148516. [P37275-1] DR Ensembl; ENST00000361642; ENSP00000354487; ENSG00000148516. [P37275-2] DR Ensembl; ENST00000446923; ENSP00000391612; ENSG00000148516. [P37275-5] DR Ensembl; ENST00000542815; ENSP00000444891; ENSG00000148516. [P37275-3] DR Ensembl; ENST00000560721; ENSP00000452787; ENSG00000148516. [P37275-4] DR GeneID; 6935; -. DR KEGG; hsa:6935; -. DR UCSC; uc001ivr.4; human. [P37275-1] DR UCSC; uc001ivu.4; human. DR CTD; 6935; -. DR GeneCards; ZEB1; -. DR HGNC; HGNC:11642; ZEB1. DR HPA; CAB058686; -. DR HPA; HPA027524; -. DR MIM; 189909; gene. DR MIM; 609141; phenotype. DR MIM; 613270; phenotype. DR neXtProt; NX_P37275; -. DR Orphanet; 98974; Fuchs endothelial corneal dystrophy. DR Orphanet; 98973; Posterior polymorphous corneal dystrophy. DR PharmGKB; PA162409589; -. DR eggNOG; KOG3623; Eukaryota. DR eggNOG; ENOG410ZFMZ; LUCA. DR GeneTree; ENSGT00630000089829; -. DR HOGENOM; HOG000264256; -. DR HOVERGEN; HBG004697; -. DR InParanoid; P37275; -. DR KO; K09299; -. DR OMA; ECEKPQG; -. DR OrthoDB; EOG790G0D; -. DR PhylomeDB; P37275; -. DR TreeFam; TF331759; -. DR SignaLink; P37275; -. DR ChiTaRS; ZEB1; human. DR EvolutionaryTrace; P37275; -. DR GeneWiki; ZEB1; -. DR GenomeRNAi; 6935; -. DR NextBio; 27137; -. DR PRO; PR:P37275; -. DR Proteomes; UP000005640; Chromosome 10. DR Bgee; P37275; -. DR CleanEx; HS_ZEB1; -. DR ExpressionAtlas; P37275; baseline and differential. DR Genevisible; P37275; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. 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:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001227; F:transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding; IDA:HGNC. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0051216; P:cartilage development; IEA:Ensembl. DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl. DR GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl. DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IEA:Ensembl. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:HGNC. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl. 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; IEA:Ensembl. DR GO; GO:0010464; P:regulation of mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; IEA:Ensembl. DR GO; GO:0033081; P:regulation of T cell differentiation in thymus; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048752; P:semicircular canal morphogenesis; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.10.60; -; 1. DR Gene3D; 3.30.160.60; -; 5. DR InterPro; IPR008598; Di19_Zn_binding_dom. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00046; Homeobox; 1. DR Pfam; PF05605; zf-Di19; 1. DR SMART; SM00389; HOX; 1. DR SMART; SM00355; ZnF_C2H2; 7. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Complete proteome; KW Corneal dystrophy; Differentiation; Disease mutation; DNA-binding; KW Homeobox; Isopeptide bond; Metal-binding; Neurogenesis; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 1124 Zinc finger E-box-binding homeobox 1. FT /FTId=PRO_0000047231. FT ZN_FING 170 193 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 200 222 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 240 262 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 268 292 C2H2-type 4; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT DNA_BIND 581 640 Homeobox; atypical. FT ZN_FING 904 926 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 932 954 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 960 981 C2H2-type 7; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT COMPBIAS 989 1124 Glu-rich (acidic). FT MOD_RES 31 31 Phosphoserine. FT {ECO:0000250|UniProtKB:Q62947}. FT MOD_RES 33 33 Phosphoserine. FT {ECO:0000250|UniProtKB:Q62947}. FT MOD_RES 313 313 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 322 322 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 642 642 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 679 679 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 686 686 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 693 693 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 700 700 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 702 702 Phosphothreonine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 704 704 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT CROSSLNK 347 347 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 493 493 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 504 504 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 515 515 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 774 774 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 1 19 MADGPRCKRRKQANPRRNN -> MK (in isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047279. FT VAR_SEQ 20 87 VTNYNTVVETNSDSDDEDKLHIVEEESVTDAADCEGVPEDD FT LPTDQTVLPGRSSEREGNAKNCWEDDR -> G (in FT isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047280. FT VAR_SEQ 87 107 RKEGQEILGPEAQADEAGCTV -> I (in isoform FT 4). {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047281. FT VAR_SEQ 87 87 R -> TG (in isoform 2 and isoform 5). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_045184. FT VARIANT 78 78 N -> T (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization; dbSNP:rs80194531). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:23599324, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063759. FT VARIANT 90 90 G -> R (in dbSNP:rs12217419). FT /FTId=VAR_052731. FT VARIANT 525 525 G -> E (found in a patient with FECD6). FT {ECO:0000269|PubMed:23599324}. FT /FTId=VAR_072897. FT VARIANT 553 553 K -> R (in dbSNP:rs35753967). FT /FTId=VAR_031824. FT VARIANT 640 640 Q -> H (in FECD6; down-regulation of FT several collagen genes expression). FT {ECO:0000269|PubMed:23599324}. FT /FTId=VAR_072898. FT VARIANT 649 649 P -> A (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063760. FT VARIANT 696 696 N -> S (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:25190660}. FT /FTId=VAR_072899. FT VARIANT 810 810 Q -> P (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063761. FT VARIANT 840 840 Q -> P (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization; dbSNP:rs118020901). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063762. FT VARIANT 905 905 A -> G (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:25190660}. FT /FTId=VAR_072900. FT VARIANT 905 905 A -> T (in FECD6). FT {ECO:0000269|PubMed:20036349}. FT /FTId=VAR_063763. FT CONFLICT 12 12 Q -> R (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 81 81 N -> S (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 84 84 E -> K (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 220 220 T -> A (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 390 390 M -> T (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 420 420 V -> I (in Ref. 2; AAA20602). FT {ECO:0000305}. FT CONFLICT 472 472 K -> R (in Ref. 3; BAG58962). FT {ECO:0000305}. FT CONFLICT 609 609 E -> Q (in Ref. 7; M81699). FT {ECO:0000305}. FT CONFLICT 654 654 I -> T (in Ref. 2; AAA20602). FT {ECO:0000305}. FT CONFLICT 672 672 D -> H (in Ref. 7; M81699). FT {ECO:0000305}. FT CONFLICT 681 681 L -> S (in Ref. 7; M81699). FT {ECO:0000305}. FT CONFLICT 775 775 K -> T (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 793 794 IP -> KY (in Ref. 3; BAG58962). FT {ECO:0000305}. FT CONFLICT 797 797 A -> N (in Ref. 3; BAG58962). FT {ECO:0000305}. FT CONFLICT 818 818 A -> V (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 838 838 I -> T (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 1066 1066 E -> G (in Ref. 3; BAC03673). FT {ECO:0000305}. FT HELIX 590 600 {ECO:0000244|PDB:2E19}. FT HELIX 608 618 {ECO:0000244|PDB:2E19}. FT HELIX 622 634 {ECO:0000244|PDB:2E19}. SQ SEQUENCE 1124 AA; 124074 MW; 0A2714CC37C848D1 CRC64; MADGPRCKRR KQANPRRNNV TNYNTVVETN SDSDDEDKLH IVEEESVTDA ADCEGVPEDD LPTDQTVLPG RSSEREGNAK NCWEDDRKEG QEILGPEAQA DEAGCTVKDD ECESDAENEQ NHDPNVEEFL QQQDTAVIFP EAPEEDQRQG TPEASGHDEN GTPDAFSQLL TCPYCDRGYK RFTSLKEHIK YRHEKNEDNF SCSLCSYTFA YRTQLERHMT SHKSGRDQRH VTQSGCNRKF KCTECGKAFK YKHHLKEHLR IHSGEKPYEC PNCKKRFSHS GSYSSHISSK KCISLIPVNG RPRTGLKTSQ CSSPSLSASP GSPTRPQIRQ KIENKPLQEQ LSVNQIKTEP VDYEFKPIVV ASGINCSTPL QNGVFTGGGP LQATSSPQGM VQAVVLPTVG LVSPISINLS DIQNVLKVAV DGNVIRQVLE NNQANLASKE QETINASPIQ QGGHSVISAI SLPLVDQDGT TKIIINYSLE QPSQLQVVPQ NLKKENPVAT NSCKSEKLPE DLTVKSEKDK SFEGGVNDST CLLCDDCPGD INALPELKHY DLKQPTQPPP LPAAEAEKPE SSVSSATGDG NLSPSQPPLK NLLSLLKAYY ALNAQPSAEE LSKIADSVNL PLDVVKKWFE KMQAGQISVQ SSEPSSPEPG KVNIPAKNND QPQSANANEP QDSTVNLQSP LKMTNSPVLP VGSTTNGSRS STPSPSPLNL SSSRNTQGYL YTAEGAQEEP QVEPLDLSLP KQQGELLERS TITSVYQNSV YSVQEEPLNL SCAKKEPQKD SCVTDSEPVV NVIPPSANPI NIAIPTVTAQ LPTIVAIADQ NSVPCLRALA ANKQTILIPQ VAYTYSTTVS PAVQEPPLKV IQPNGNQDER QDTSSEGVSN VEDQNDSDST PPKKKMRKTE NGMYACDLCD KIFQKSSSLL RHKYEHTGKR PHECGICKKA FKHKHHLIEH MRLHSGEKPY QCDKCGKRFS HSGSYSQHMN HRYSYCKREA EERDSTEQEE AGPEILSNEH VGARASPSQG DSDERESLTR EEDEDSEKEE EEEDKEMEEL QEEKECEKPQ GDEEEEEEEE EVEEEEVEEA ENEGEEAKTE GLMKDDRAES QASSLGQKVG ESSEQVSEEK TNEA // ID ZEB2_HUMAN Reviewed; 1214 AA. AC O60315; A0JP09; B7Z2P2; F5H814; Q9UED1; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 11-NOV-2015, entry version 167. DE RecName: Full=Zinc finger E-box-binding homeobox 2; DE AltName: Full=Smad-interacting protein 1; DE Short=SMADIP1; DE AltName: Full=Zinc finger homeobox protein 1b; GN Name=ZEB2; Synonyms=KIAA0569, SIP1, ZFHX1B, ZFX1B; GN ORFNames=HRIHFB2411; 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], AND INVOLVEMENT IN MOWS. RX PubMed=11448942; DOI=10.1093/hmg/10.14.1503; RA Cacheux V., Dastot-Le Moal F., Kaeaeriaeinen H., Bondurand N., RA Rintala R., Boissier B., Wilson M., Mowat D., Goossens M.; RT "Loss-of-function mutations in SIP1 Smad interacting protein 1 result RT in a syndromic Hirschsprung disease."; RL Hum. Mol. Genet. 10:1503-1510(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=11279515; DOI=10.1038/86860; RA Wakamatsu N., Yamada Y., Yamada K., Ono T., Nomura N., Taniguchi H., RA Kitoh H., Mutoh N., Yamanaka T., Mushiake K., Kato K., Sonta S., RA Nagaya M.; RT "Mutations in SIP1, encoding Smad interacting protein 1, cause a form RT of Hirschsprung disease."; RL Nat. Genet. 27:369-370(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. RT The complete sequences of 100 new cDNA clones from brain which can RT code for large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [4] 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [LARGE SCALE MRNA] OF 1161-1214 (ISOFORM 1), AND RP SUBCELLULAR LOCATION. RC TISSUE=Fetal brain; RX PubMed=9853615; DOI=10.1038/4315; RA Ueki N., Oda T., Kondo M., Yano K., Noguchi T., Muramatsu M.-A.; RT "Selection system for genes encoding nuclear-targeted proteins."; RL Nat. Biotechnol. 16:1338-1342(1998). RN [8] RP FUNCTION, SUMOYLATION AT LYS-391 AND LYS-866, INTERACTION WITH CBX4 RP AND CTBP1, AND SUBCELLULAR LOCATION. 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 [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-377, 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 [10] 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 [11] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-391 AND LYS-866, 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 [12] RP STRUCTURE BY NMR OF 647-705. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the homeobox domain of zinc finger homeobox RT protein 1B (SMAD interacting protein 1)."; RL Submitted (DEC-2006) to the PDB data bank. RN [13] RP VARIANT MOWS ASN-99 DEL. RX PubMed=12451214; DOI=10.1212/01.WNL.0000034842.78350.4E; RA Yoneda M., Fujita T., Yamada Y., Yamada K., Fujii A., Inagaki T., RA Nakagawa H., Shimada A., Kishikawa M., Nagaya M., Azuma T., RA Kuriyama M., Wakamatsu N.; RT "Late infantile Hirschsprung disease-mental retardation syndrome with RT a 3-bp deletion in ZFHX1B."; RL Neurology 59:1637-1640(2002). RN [14] RP VARIANT MOWS GLY-953. RX PubMed=15384097; DOI=10.1002/ajmg.a.30312; RA Gregory-Evans C.Y., Vieira H., Dalton R., Adams G.G.W., Salt A., RA Gregory-Evans K.; RT "Ocular coloboma and high myopia with Hirschsprung disease associated RT with a novel ZFHX1B missense mutation and trisomy 21."; RL Am. J. Med. Genet. A 131:86-90(2004). RN [15] RP VARIANT MOWS ARG-1119. RX PubMed=16688751; DOI=10.1002/ajmg.a.31267; RA Heinritz W., Zweier C., Froster U.G., Strenge S., Kujat A., Syrbe S., RA Rauch A., Schuster V.; RT "A missense mutation in the ZFHX1B gene associated with an atypical RT Mowat-Wilson syndrome phenotype."; RL Am. J. Med. Genet. A 140:1223-1227(2006). RN [16] RP VARIANT [LARGE SCALE ANALYSIS] ASN-983. 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). CC -!- FUNCTION: Transcriptional inhibitor that binds to DNA sequence 5'- CC CACCT-3' in different promoters. Represses transcription of E- CC cadherin. {ECO:0000269|PubMed:16061479}. CC -!- SUBUNIT: Binds activated SMAD1, activated SMAD2 and activated CC SMAD3; binding with SMAD4 is not detected (By similarity). CC Interacts with CBX4 and CTBP1. {ECO:0000250, CC ECO:0000269|PubMed:16061479}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16061479, CC ECO:0000269|PubMed:9853615}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O60315-1; Sequence=Displayed; CC Name=2; CC IsoId=O60315-2; Sequence=VSP_044797; CC Note=No experimental confirmation available.; CC -!- PTM: Sumoylation on Lys-391 and Lys-866 is promoted by the E3 CC SUMO-protein ligase CBX4, and impairs interaction with CTBP1 and CC transcription repression activity. {ECO:0000269|PubMed:16061479}. CC -!- DISEASE: Mowat-Wilson syndrome (MOWS) [MIM:235730]: A complex CC developmental disorder characterized by mental retardation, CC delayed motor development, epilepsy, microcephaly and a wide CC spectrum of clinically heterogeneous features suggestive of CC neurocristopathies at the cephalic, cardiac, and vagal levels. CC Affected patients show an easily recognizable facial appearance CC with deep set eyes and hypertelorism, medially divergent, broad CC eyebrows, prominent columella, pointed chin and uplifted, notched CC ear lobes. Some patients manifest Hirschsprung disease. CC {ECO:0000269|PubMed:11448942, ECO:0000269|PubMed:12451214, CC ECO:0000269|PubMed:15384097, ECO:0000269|PubMed:16688751}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 8 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA25495.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; 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; AY029472; AAK52081.1; -; Genomic_DNA. DR EMBL; AB056507; BAB40819.1; -; mRNA. DR EMBL; AB011141; BAA25495.2; ALT_INIT; mRNA. DR EMBL; AK294928; BAH11928.1; -; mRNA. DR EMBL; AC009951; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC010130; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC127102; AAI27103.1; -; mRNA. DR EMBL; AB015341; BAA34798.1; -; mRNA. DR CCDS; CCDS2186.1; -. [O60315-1] DR CCDS; CCDS54403.1; -. [O60315-2] DR RefSeq; NP_001165124.1; NM_001171653.1. [O60315-2] DR RefSeq; NP_055610.1; NM_014795.3. [O60315-1] DR RefSeq; XP_006712944.1; XM_006712881.2. [O60315-1] DR RefSeq; XP_006712945.1; XM_006712882.2. [O60315-1] DR UniGene; Hs.34871; -. DR PDB; 2DA7; NMR; -; A=647-704. DR PDBsum; 2DA7; -. DR ProteinModelPortal; O60315; -. DR SMR; O60315; 648-705. DR BioGrid; 115175; 20. DR IntAct; O60315; 11. DR MINT; MINT-1181379; -. DR STRING; 9606.ENSP00000302501; -. DR PhosphoSite; O60315; -. DR BioMuta; ZEB2; -. DR MaxQB; O60315; -. DR PaxDb; O60315; -. DR PRIDE; O60315; -. DR Ensembl; ENST00000409487; ENSP00000386854; ENSG00000169554. [O60315-1] DR Ensembl; ENST00000539609; ENSP00000443792; ENSG00000169554. [O60315-2] DR Ensembl; ENST00000558170; ENSP00000454157; ENSG00000169554. [O60315-1] DR Ensembl; ENST00000627532; ENSP00000487174; ENSG00000169554. [O60315-1] DR GeneID; 9839; -. DR KEGG; hsa:9839; -. DR UCSC; uc002tvu.3; human. [O60315-1] DR CTD; 9839; -. DR GeneCards; ZEB2; -. DR GeneReviews; ZEB2; -. DR HGNC; HGNC:14881; ZEB2. DR HPA; HPA003456; -. DR MIM; 235730; phenotype. DR MIM; 605802; gene. DR neXtProt; NX_O60315; -. DR Orphanet; 261552; Mowat-Wilson syndrome due to a ZEB2 point mutation. DR Orphanet; 261537; Mowat-Wilson syndrome due to monosomy 2q22. DR PharmGKB; PA162409612; -. DR eggNOG; ENOG410IMF7; Eukaryota. DR eggNOG; ENOG410ZQ40; LUCA. DR GeneTree; ENSGT00630000089829; -. DR HOGENOM; HOG000264256; -. DR HOVERGEN; HBG004697; -. DR InParanoid; O60315; -. DR KO; K09299; -. DR OMA; LDHSRSN; -. DR OrthoDB; EOG790G0D; -. DR PhylomeDB; O60315; -. DR TreeFam; TF331759; -. DR SignaLink; O60315; -. DR ChiTaRS; ZEB2; human. DR EvolutionaryTrace; O60315; -. DR GeneWiki; ZEB2; -. DR GenomeRNAi; 9839; -. DR NextBio; 37070; -. DR PRO; PR:O60315; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; O60315; -. DR CleanEx; HS_SIP1; -. DR CleanEx; HS_ZEB2; -. DR ExpressionAtlas; O60315; baseline and differential. DR Genevisible; O60315; HS. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0019208; F:phosphatase regulator activity; NAS:UniProtKB. DR GO; GO:0048066; P:developmental pigmentation; ISS:BHF-UCL. DR GO; GO:0097324; P:melanocyte migration; ISS:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0007399; P:nervous system development; NAS:UniProtKB. DR GO; GO:0048023; P:positive regulation of melanin biosynthetic process; IC:BHF-UCL. DR GO; GO:0045636; P:positive regulation of melanocyte differentiation; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0050790; P:regulation of catalytic activity; NAS:GOC. DR GO; GO:1903056; P:regulation of melanosome organization; ISS:BHF-UCL. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 5. DR InterPro; IPR008598; Di19_Zn_binding_dom. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF05605; zf-Di19; 1. DR SMART; SM00389; HOX; 1. DR SMART; SM00355; ZnF_C2H2; 8. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Disease mutation; DNA-binding; Epilepsy; Hirschsprung disease; KW Homeobox; Isopeptide bond; Mental retardation; Metal-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 1214 Zinc finger E-box-binding homeobox 2. FT /FTId=PRO_0000047236. FT ZN_FING 211 234 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 241 263 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 282 304 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 310 334 C2H2-type 4; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT ZN_FING 581 605 C2H2-type 5; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT DNA_BIND 644 703 Homeobox; atypical. FT ZN_FING 999 1021 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 1027 1049 C2H2-type 7. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 1055 1076 C2H2-type 8; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT REGION 437 487 SMAD-MH2 binding domain. {ECO:0000250}. FT COMPBIAS 1084 1214 Glu-rich (acidic). FT MOD_RES 356 356 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT MOD_RES 360 360 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT MOD_RES 364 364 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT MOD_RES 377 377 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 731 731 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT MOD_RES 780 780 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT MOD_RES 784 784 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT MOD_RES 1124 1124 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT MOD_RES 1203 1203 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R0G7}. FT CROSSLNK 391 391 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. FT CROSSLNK 391 391 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447}. FT CROSSLNK 866 866 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. FT CROSSLNK 866 866 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 111 134 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_044797. FT VARIANT 99 99 Missing (in MOWS). FT {ECO:0000269|PubMed:12451214}. FT /FTId=VAR_027016. FT VARIANT 953 953 R -> G (in MOWS). FT {ECO:0000269|PubMed:15384097}. FT /FTId=VAR_027017. FT VARIANT 983 983 D -> N (in a colorectal cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035563. FT VARIANT 1119 1119 Q -> R (in MOWS). FT {ECO:0000269|PubMed:16688751}. FT /FTId=VAR_027018. FT CONFLICT 1155 1155 D -> G (in Ref. 4; BAH11928). FT {ECO:0000305}. FT HELIX 654 665 FT HELIX 671 681 FT HELIX 685 700 SQ SEQUENCE 1214 AA; 136447 MW; B578FD91339C3FDD CRC64; MKQPIMADGP RCKRRKQANP RRKNVVNYDN VVDTGSETDE EDKLHIAEDD GIANPLDQET SPASVPNHES SPHVSQALLP REEEEDEIRE GGVEHPWHNN EILQASVDGP EEMKEDYDTM GPEATIQTAI NNGTVKNANC TSDFEEYFAK RKLEERDGHA VSIEEYLQRS DTAIIYPEAP EELSRLGTPE ANGQEENDLP PGTPDAFAQL LTCPYCDRGY KRLTSLKEHI KYRHEKNEEN FSCPLCSYTF AYRTQLERHM VTHKPGTDQH QMLTQGAGNR KFKCTECGKA FKYKHHLKEH LRIHSGEKPY ECPNCKKRFS HSGSYSSHIS SKKCIGLISV NGRMRNNIKT GSSPNSVSSS PTNSAITQLR NKLENGKPLS MSEQTGLLKI KTEPLDFNDY KVLMATHGFS GTSPFMNGGL GATSPLGVHP SAQSPMQHLG VGMEAPLLGF PTMNSNLSEV QKVLQIVDNT VSRQKMDCKA EEISKLKGYH MKDPCSQPEE QGVTSPNIPP VGLPVVSHNG ATKSIIDYTL EKVNEAKACL QSLTTDSRRQ ISNIKKEKLR TLIDLVTDDK MIENHNISTP FSCQFCKESF PGPIPLHQHE RYLCKMNEEI KAVLQPHENI VPNKAGVFVD NKALLLSSVL SEKGMTSPIN PYKDHMSVLK AYYAMNMEPN SDELLKISIA VGLPQEFVKE WFEQRKVYQY SNSRSPSLER SSKPLAPNSN PPTKDSLLPR SPVKPMDSIT SPSIAELHNS VTNCDPPLRL TKPSHFTNIK PVEKLDHSRS NTPSPLNLSS TSSKNSHSSS YTPNSFSSEE LQAEPLDLSL PKQMKEPKSI IATKNKTKAS SISLDHNSVS SSSENSDEPL NLTFIKKEFS NSNNLDNKST NPVFSMNPFS AKPLYTALPP QSAFPPATFM PPVQTSIPGL RPYPGLDQMS FLPHMAYTYP TGAATFADMQ QRRKYQRKQG FQGELLDGAQ DYMSGLDDMT DSDSCLSRKK IKKTESGMYA CDLCDKTFQK SSSLLRHKYE HTGKRPHQCQ ICKKAFKHKH HLIEHSRLHS GEKPYQCDKC GKRFSHSGSY SQHMNHRYSY CKREAEEREA AEREAREKGH LEPTELLMNR AYLQSITPQG YSDSEERESM PRDGESEKEH EKEGEDGYGK LGRQDGDEEF EEEEEESENK SMDTDPETIR DEEETGDHSM DDSSEDGKME TKSDHEEDNM EDGM // ID ZFH1_DROME Reviewed; 1054 AA. AC P28166; Q59DT3; Q6NP51; Q8MSQ8; Q9VA39; Q9VA40; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2004, sequence version 2. DT 11-NOV-2015, entry version 148. DE RecName: Full=Zinc finger protein 1; DE AltName: Full=Zinc finger homeodomain protein 1; GN Name=zfh1; Synonyms=zfh-1; ORFNames=CG1322; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; OC Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=1680376; DOI=10.1016/0925-4773(91)90048-B; RA Fortini M.E., Lai Z., Rubin G.M.; RT "The Drosophila zfh-1 and zfh-2 genes encode novel proteins containing RT both zinc-finger and homeodomain motifs."; RL Mech. Dev. 34:113-122(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., RA Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [3] RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 30-1054 (ISOFORM B). RC STRAIN=Berkeley; TISSUE=Embryo; RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., RA Champe M., Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., RA George R.A., Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., RA Miranda A., Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., RA Patel S., Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., RA Celniker S.E.; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 540-1054. RC STRAIN=Berkeley; TISSUE=Embryo; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582; SER-586 AND RP SER-934, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryo; RX PubMed=18327897; DOI=10.1021/pr700696a; RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.; RT "Phosphoproteome analysis of Drosophila melanogaster embryos."; RL J. Proteome Res. 7:1675-1682(2008). CC -!- FUNCTION: Involved in the development of the embryonic central CC nervous system, embryonic mesoderm and adult musculature. CC {ECO:0000269|PubMed:1680376}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=B; CC IsoId=P28166-1; Sequence=Displayed; CC Name=A; CC IsoId=P28166-2; Sequence=VSP_009670, VSP_009671; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Mesoderm and mesodermally-derived structures CC in the embryo including the dorsal vessel, support cells of the CC gonads, and segment-specific arrays of adult muscle precursor. CC Also identified in motor neurons of developing CNS. CC {ECO:0000269|PubMed:1680376}. CC -!- SIMILARITY: Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 9 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. CC -!- SEQUENCE CAUTION: CC Sequence=AAM50023.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; 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; M63449; AAA29050.1; -; Genomic_DNA. DR EMBL; AE014297; AAF57083.1; -; Genomic_DNA. DR EMBL; AE014297; AAF57084.1; -; Genomic_DNA. DR EMBL; BT003277; AAO25034.1; -; mRNA. DR EMBL; BT011080; AAR82746.1; -; mRNA. DR EMBL; AY118654; AAM50023.1; ALT_SEQ; mRNA. DR PIR; S33641; S33641. DR RefSeq; NP_476850.1; NM_057502.5. [P28166-1] DR RefSeq; NP_733402.1; NM_170523.3. [P28166-2] DR UniGene; Dm.4708; -. DR ProteinModelPortal; P28166; -. DR SMR; P28166; 289-404, 694-756, 920-1053. DR BioGrid; 68501; 14. DR IntAct; P28166; 5. DR MINT; MINT-94472; -. DR STRING; 7227.FBpp0303607; -. DR PaxDb; P28166; -. DR GeneID; 43650; -. DR KEGG; dme:Dmel_CG1322; -. DR CTD; 43650; -. DR FlyBase; FBgn0004606; zfh1. DR eggNOG; KOG3623; Eukaryota. DR eggNOG; ENOG410ZFMZ; LUCA. DR InParanoid; P28166; -. DR KO; K09299; -. DR OrthoDB; EOG7C5M7G; -. DR PhylomeDB; P28166; -. DR SignaLink; P28166; -. DR GenomeRNAi; 43650; -. DR NextBio; 835065; -. DR PRO; PR:P28166; -. DR Proteomes; UP000000803; Chromosome 3R. DR Bgee; P28166; -. DR Genevisible; P28166; DM. DR GO; GO:0005634; C:nucleus; IDA:FlyBase. DR GO; GO:0003677; F:DNA binding; TAS:FlyBase. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:FlyBase. DR GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:FlyBase. DR GO; GO:0019730; P:antimicrobial humoral response; IMP:FlyBase. DR GO; GO:0061321; P:garland nephrocyte differentiation; IMP:FlyBase. DR GO; GO:0008354; P:germ cell migration; IMP:FlyBase. DR GO; GO:0008406; P:gonad development; TAS:FlyBase. DR GO; GO:0007507; P:heart development; NAS:FlyBase. DR GO; GO:0007516; P:hemocyte development; IMP:FlyBase. DR GO; GO:0048542; P:lymph gland development; IMP:FlyBase. DR GO; GO:0007498; P:mesoderm development; IGI:FlyBase. DR GO; GO:0008045; P:motor neuron axon guidance; IMP:FlyBase. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:FlyBase. DR GO; GO:0007399; P:nervous system development; IEP:FlyBase. DR GO; GO:0007280; P:pole cell migration; TAS:FlyBase. DR GO; GO:0048103; P:somatic stem cell division; IMP:FlyBase. DR Gene3D; 1.10.10.60; -; 1. DR Gene3D; 3.30.160.60; -; 5. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00046; Homeobox; 1. DR SMART; SM00389; HOX; 1. DR SMART; SM00355; ZnF_C2H2; 9. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 9. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; DNA-binding; Homeobox; KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Zinc; Zinc-finger. FT CHAIN 1 1054 Zinc finger protein 1. FT /FTId=PRO_0000047241. FT ZN_FING 74 97 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 289 311 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 324 346 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 355 377 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 383 407 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 628 651 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT DNA_BIND 699 758 Homeobox. {ECO:0000255|PROSITE- FT ProRule:PRU00108}. FT ZN_FING 967 989 C2H2-type 7. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 995 1017 C2H2-type 8. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 1023 1044 C2H2-type 9. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT COMPBIAS 222 246 Gln-rich (OPA repeat). FT MOD_RES 582 582 Phosphoserine. FT {ECO:0000269|PubMed:18327897}. FT MOD_RES 586 586 Phosphoserine. FT {ECO:0000269|PubMed:18327897}. FT MOD_RES 934 934 Phosphoserine. FT {ECO:0000269|PubMed:18327897}. FT VAR_SEQ 1 307 Missing (in isoform A). FT {ECO:0000303|Ref.4}. FT /FTId=VSP_009670. FT VAR_SEQ 308 324 EQLHSPCGPAAVSNVSQ -> MSAAACLLSSSTSSFEK FT (in isoform A). {ECO:0000303|Ref.4}. FT /FTId=VSP_009671. FT CONFLICT 78 78 Q -> K (in Ref. 4; AAR82746). FT {ECO:0000305}. FT CONFLICT 147 147 S -> T (in Ref. 4; AAR82746). FT {ECO:0000305}. FT CONFLICT 239 239 Q -> QMQQQQQ (in Ref. 1; AAA29050). FT {ECO:0000305}. FT CONFLICT 625 625 A -> S (in Ref. 1; AAA29050, 4; AAR82746 FT and 5; AAM50023). {ECO:0000305}. FT CONFLICT 954 954 A -> V (in Ref. 1; AAA29050). FT {ECO:0000305}. SQ SEQUENCE 1054 AA; 116598 MW; 5189AB2214AB5B8B CRC64; MLSCLAPSSS RFGQEDTIIQ QSMPSTSPFA MQFPSLASTL LHHNQSPKHS NPGSSGIQDA HPNQPGAAAD AFLVKCTQCH KRFPEYQSLS EHIASEHPHD KLNCGAAQPE SDAEDEQSNM SGSSRRYAKS PLASNNNSST ANANNNSTSS QSMNNNSELA KNHNSANKMS PMCSPGSLTP GDLFAQLQHP PPQLPPHLHA QFMAAAASLA MQSARTASSP SQQQQQQLQQ QQQLQQQQQH QMAMQQLLPP QLPGSNSSVG SNSAYDLDLS APRSTSSPGS TTGDLSGAYP CMQCTASFAS REQLEQHEQL HSPCGPAAVS NVSQTCRICH KAFANVYRLQ RHMISHDESA LLRKFKCKEC DKAFKFKHHL KEHVRIHSGE KPFGCDNCGK RFSHSGSFSS HMTSKKCISM GLKLNNNRAL LKRLEKSPGS ASSASRRSPS DHGKGKLPEQ PSLPGLPHPM SYFASDAQVQ GGSAAPAPFP PFHPNYMNAA LLAFPHNFMA AAAGLDPRVH PYSIQRLLQL SAAGQQQREE EREEQQKQQQ HDEEETPDEP KLVMDIEEPE TKEMAPTPEA TEAATPIKRE ESREASPDPE SYRSSSQAIK QEQEPLNVAE ERQTPVEEHA PVEHAADLRC SRCSKQFNHP TELVQHEKVL CGLIKEELEQ HFQQQQATSF ALASASEEDE EDEEMDVEEE PRQESGERKV RVRTAINEEQ QQQLKQHYSL NARPSRDEFR MIAARLQLDP RVVQVWFQNN RSRERKMQSF QNNQAAGAAP PMPIDSQASL TREDQPLDLS VKRDPLTPKS ESSPPYIAPP SGEALNPEAI NLSRKFSTSA SMSPASISPS SAAALYFGAA PPPSPPNSQL DSTPRSGQAF PGLPPYMLPM SLPMEALFKM RPGGDFASNH ALMNSIKLPD YRGTSLSPGG SEKRSWRDDD SRISHEDEFG AGVLMPPKPR RGKAETHGHA GDPDLPYVCD QCDKAFAKQS SLARHKYEHS GQRPYQCIEC PKAFKHKHHL TEHKRLHSGE KPFQCSKCLK RFSHSGSYSQ HMNHRYSYCK PYRE // ID Q91647_XENLA Unreviewed; 521 AA. AC Q91647; DT 01-NOV-1996, integrated into UniProtKB/TrEMBL. DT 01-NOV-1996, sequence version 1. DT 11-NOV-2015, entry version 75. DE SubName: Full=XPolycomb {ECO:0000313|EMBL:AAC59728.1}; GN Name=cbx4 {ECO:0000313|Xenbase:XB-GENE-986722}; GN Synonyms=XPolycomb {ECO:0000313|EMBL:AAC59728.1}; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Amphibia; Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; OC Xenopus. OX NCBI_TaxID=8355 {ECO:0000313|EMBL:AAC59728.1}; RN [1] {ECO:0000313|EMBL:AAC59728.1} RP NUCLEOTIDE SEQUENCE. RX PubMed=8555110; DOI=10.1016/0925-4773(95)00422-X; RA Reijnen M.J., Hamer K.M., den Blaauwen J.L., Lambrechts C., RA Schoneveld I., van Driel R., Otte A.P.; RT "Polycomb and bmi-1 homologs are expressed in overlapping patterns in RT Xenopus embryos and are able to interact with each other."; RL Mech. Dev. 53:35-46(1995). 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; U39929; AAC59728.1; -; mRNA. DR PIR; I51693; I51693. DR RefSeq; NP_001080949.1; NM_001087480.1. DR UniGene; Xl.338; -. DR ProteinModelPortal; Q91647; -. DR SMR; Q91647; 8-65. DR GeneID; 394294; -. DR KEGG; xla:394294; -. DR CTD; 8535; -. DR Xenbase; XB-GENE-986722; cbx4. DR HOVERGEN; HBG005257; -. DR KO; K11452; -. DR GO; GO:0005634; C:nucleus; 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 2: Evidence at transcript level; KW Nucleus {ECO:0000256|SAAS:SAAS00010661}. SQ SEQUENCE 521 AA; 58804 MW; 1AC11753EEF79B56 CRC64; MELPAVGEHV FAVESIEKKR IRKGRVEYLV KWRGWSSKYN TWEPEENILD PRLLVAFQNR ERQEQIMGYR KRGPKPKNNL VSMPSFARRS NVLSGLHDSS GENRTKLDLG PIPKSHQYQL NSKKHHQYQP SGKDHNEKHH SSNKKKYYYQ LNSKKHHHYQ PDPKLYEQYT IEKESQISTD VRNRHRDSLT HTQAADMGTQ LKNGTDSVIS GPERNGICNG VSSSPSTEMS SSPSTELSSS PSTELPSSGV GGKMKIVKNK NKNGRIVIVM SKYMENGMQS VKIKSSEEDC DMGDVRRRFD SPGTLNGDKT CTAQEEKTEH WKKRVESRVK IHEGSKSVDK GSVHLAGLRR TYSTASETLN DQPLQLTTKS SHVPMPNRTR SPVYAGEPYN DLVYTNPRKR CLSEANGNKE LCKKTLTSRS VSAPGIVECK GGLTPLNVPL QEPDIILLDS DLDEPIDLRC VKSRCDSDQE VDKPEIQVTQ NPQSVDVDVC ESQFKPFFGN IVITDVTANC LTVTFKEYIT V //