E1A_ADE02
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 25-MAY-2022, entry version 124.
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; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC Rowavirales; 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 AND
RP 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; EARLY
RP E1A 26 KDA PROTEIN AND EARLY E1A 6 KDA PROTEIN).
RX PubMed=7142161; DOI=10.1016/s0021-9258(18)33473-2;
RA Gingeras T.R., Sciaky D., Gelinas R.E., Bing-Dong J., Yen C.E., Kelly M.M.,
RA 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; DOI=10.1128/mcb.13.1.561-570.1993;
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 which
RT can directly associate with E1a.";
RL Mol. Cell. Biol. 13:561-570(1993).
CC -!- FUNCTION: Plays a role in viral genome replication by driving entry of
CC quiescent cells into the cell cycle. Stimulation of progression from G1
CC to S phase allows the virus to efficiently use the cellular DNA
CC replicating machinery to achieve viral genome replication. E1A protein
CC has both transforming and trans-activating activities. Induces the
CC disassembly of the E2F1 transcription factor from RB1 by direct
CC competition for the same binding site on RB1, with subsequent
CC transcriptional activation of E2F1-regulated S-phase genes and of the
CC E2 region of the adenoviral genome. Release of E2F1 leads to the ARF-
CC mediated inhibition of MDM2 and causes TP53/p53 to accumulate because
CC it is 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 by
CC the viral protein E1B-55K. Inactivation of the ability of RB1 to arrest
CC the cell cycle is critical for cellular transformation, uncontrolled
CC cellular growth and proliferation induced by viral infection.
CC Interaction with RBX1 and CUL1 inhibits ubiquitination of the proteins
CC targeted by SCF(FBXW7) ubiquitin ligase complex, and may be linked to
CC unregulated host cell proliferation. The tumorigenesis-restraining
CC activity of E1A may be related to the disruption of the host CtBP-CtIP
CC complex through the CtBP binding motif. Interacts with host TBP
CC protein; this interaction probably disrupts the TBP-TATA complex.
CC Interaction with host TMEM173/STING impairs the ability of
CC TMEM173/STING to sense cytosolic DNA and promote the production of type
CC I interferon (IFN-alpha and IFN-beta). Promotes the sumoylation of host
CC ZBED1/hDREF with SUMO1 (By similarity). {ECO:0000250|UniProtKB:P03255}.
CC -!- SUBUNIT: Interacts with host UBE2I; this interaction interferes with
CC polySUMOylation. Interacts with host RB1; this interaction induces the
CC aberrant dissociation of RB1-E2F1 complex thereby disrupting the
CC activity of RB1 and activating E2F1-regulated genes. Interacts with
CC host ATF7; the interaction enhances ATF7-mediated viral transactivation
CC activity which requires the zinc binding domains of both proteins
CC (PubMed:8417352). Isoform early E1A 32 kDa protein and isoform early
CC E1A 26 kDa protein interact (via N-terminus) with CUL1 and E3 ubiquitin
CC ligase RBX1; these interactions inhibit RBX1-CUL1-dependent elongation
CC reaction of ubiquitin chains and attenuate ubiquitination of SCF(FBXW7)
CC target proteins. Interacts (via PXLXP motif) with host ZMYND11/BS69
CC (via MYND-type zinc finger); this interaction inhibits E1A mediated
CC transactivation. Interacts with host EP300; this interaction stimulates
CC the acetylation of RB1 by recruiting EP300 and RB1 into a multimeric-
CC protein complex. Interacts with host CTBP1 and CTBP2; this interaction
CC seems to potentiate viral replication. Interacts with host DCAF7.
CC Interacts with host DYRK1A. Interacts with host KPNA4; this interaction
CC allows E1A import into the host nucleus. Interacts with host EP400;
CC this interaction stabilizes MYC. Interacts (via LXCXE motif) with host
CC TMEM173/STING; this interaction impairs the ability of TMEM173/STING to
CC sense cytosolic DNA and promote the production of type I interferon
CC (IFN-alpha and IFN-beta) (By similarity). Interacts (via C-terminus)
CC with host ZBED1/hDREF (via C-terminus); the interaction is direct (By
CC similarity). {ECO:0000250|UniProtKB:P03255,
CC ECO:0000269|PubMed:8417352}.
CC -!- INTERACTION:
CC P03254; P45481: Crebbp; Xeno; NbExp=3; IntAct=EBI-8599077, EBI-296306;
CC P03254; P06400: RB1; Xeno; NbExp=3; IntAct=EBI-8599077, EBI-491274;
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}.
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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 BMRB; P03254; -.
DR SMR; P03254; -.
DR DIP; DIP-570N; -.
DR ELM; P03254; -.
DR IntAct; P03254; 3.
DR MINT; P03254; -.
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:0039648; P:modulation by virus of host protein ubiquitination; 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:InterPro.
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 JAK-STAT cascade via inhibition of 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 DisProt; DP01928; -.
DR InterPro; IPR014410; Aden_E1A.
DR Pfam; PF02703; Adeno_E1A; 1.
DR PIRSF; PIRSF003669; Aden_E1A; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; 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; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..289
FT /note="Early E1A protein"
FT /id="PRO_0000221692"
FT ZN_FING 154..174
FT /evidence="ECO:0000250|UniProtKB:P03255"
FT REGION 41..49
FT /note="Interaction with RB1 in competition with E2F1"
FT /evidence="ECO:0000250"
FT REGION 76..140
FT /note="Interaction with UBE2I"
FT /evidence="ECO:0000250"
FT REGION 82..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 113..117
FT /note="PXLXP motif, interaction with host ZMYND11"
FT /evidence="ECO:0000250"
FT MOTIF 122..126
FT /note="LXCXE motif, interaction with host RB1 and
FT TMEM173/STING"
FT /evidence="ECO:0000255"
FT MOTIF 258..289
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P03255, ECO:0000255"
FT MOTIF 279..283
FT /note="PXDLS motif, CTBP-binding"
FT /evidence="ECO:0000250|UniProtKB:P03255"
FT COMPBIAS 220..238
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 89
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 219
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT MOD_RES 231
FT /note="Phosphoserine; by host"
FT /evidence="ECO:0000250"
FT VAR_SEQ 29..55
FT /note="ADNLPPPSHFEPPTLHELYDLDVTAPE -> CLNLSLSPSQNRSLQDLPGVL
FT NWCLLS (in isoform early E1A 6 kDa protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_028916"
FT VAR_SEQ 56..289
FT /note="Missing (in isoform early E1A 6 kDa protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_028917"
FT VAR_SEQ 140..185
FT /note="Missing (in isoform early E1A 26 kDa protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_000197"
FT MUTAGEN 157
FT /note="C->S: Abolishes ATF7-mediated transcriptional
FT activation."
FT /evidence="ECO:0000269|PubMed:8417352"
FT MUTAGEN 178
FT /note="T->P: No effect on ATF7-mediated transcriptional
FT activation."
FT /evidence="ECO:0000269|PubMed:8417352"
FT MUTAGEN 185
FT /note="S->R: Abolishes ATF7-mediated transcriptional
FT activation."
FT /evidence="ECO:0000269|PubMed:8417352"
FT CONFLICT 68
FT /note="D -> E (in Ref. 2; AAA92197/AAA92199)"
FT /evidence="ECO:0000305"
FT CONFLICT 81
FT /note="L -> F (in Ref. 2; AAA92197/AAA92199)"
FT /evidence="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
