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 //