E1A_ADE07
ID E1A_ADE07 Reviewed; 261 AA.
AC P03256; P03257;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 23-FEB-2022, entry version 93.
DE RecName: Full=Early E1A protein;
DE AltName: Full=Early E1A 28 kDa protein;
OS Human adenovirus B serotype 7 (HAdV-7) (Human adenovirus 7).
OC Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC Rowavirales; Adenoviridae; Mastadenovirus; Human mastadenovirus B.
OX NCBI_TaxID=10519;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS EARLY E1A 28 KDA PROTEIN; EARLY
RP E1A 24 KDA PROTEIN AND EARLY E1A 6.3 KDA PROTEIN).
RC STRAIN=Gomen;
RX PubMed=6985480; DOI=10.1016/0378-1119(80)90112-2;
RA Dijkema R., Dekker B.M.M., van Ormondt H., de Waard A., Maat J.,
RA Boyer H.W.;
RT "Gene organization of the transforming region of weakly oncogenic
RT adenovirus type 7: the E1a region.";
RL Gene 12:287-299(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS EARLY E1A 28 KDA PROTEIN; EARLY
RP E1A 24 KDA PROTEIN AND EARLY E1A 6.3 KDA PROTEIN).
RC STRAIN=Grider;
RA Yoshida K., Fujinaga K.;
RT "The nucleotide sequence of the transforming HindIII-I.J fragment of
RT adenovirus type 7 DNA.";
RL Tumor Res. 19:39-47(1984).
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. Interaction with host
CC TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic
CC DNA and promote the production of type I interferon (IFN-alpha and IFN-
CC beta). Promotes the sumoylation of host ZBED1/hDREF with SUMO1 (By
CC 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 Isoform early E1A 32 kDa protein and isoform early E1A 26 kDa protein
CC interact (via N-terminus) with CUL1 and E3 ubiquitin ligase RBX1; these
CC interactions inhibit RBX1-CUL1-dependent elongation reaction of
CC ubiquitin chains and attenuate ubiquitination of SCF(FBXW7) target
CC proteins. Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-
CC 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 with host TBP protein; this
CC interaction probably disrupts the TBP-TATA complex. Interacts (via
CC LXCXE motif) with host TMEM173/STING; this interaction impairs the
CC ability of TMEM173/STING to sense cytosolic DNA and promote the
CC production of type I interferon (IFN-alpha and IFN-beta). Interacts
CC (via C-terminus) with host ZBED1/hDREF (via C-terminus); the
CC interaction is direct (By similarity). {ECO:0000250|UniProtKB:P03254,
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 28 kDa protein;
CC IsoId=P03256-1; Sequence=Displayed;
CC Name=early E1A 24 kDa protein;
CC IsoId=P03256-2; Sequence=VSP_000199;
CC Name=early E1A 6.3 kDa protein;
CC IsoId=P03256-3; Sequence=VSP_028920, VSP_028921;
CC -!- SIMILARITY: Belongs to the adenoviridae E1A protein family.
CC {ECO:0000305}.
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DR EMBL; X03000; CAA26758.1; -; Genomic_DNA.
DR EMBL; X03000; CAA26759.1; -; Genomic_DNA.
DR EMBL; X03000; CAA26760.1; -; Genomic_DNA.
DR EMBL; M38648; AAA42453.1; -; Genomic_DNA.
DR EMBL; M38648; AAA42454.1; -; Genomic_DNA.
DR EMBL; M38648; AAA42455.1; -; Genomic_DNA.
DR PIR; A03826; WMAD87.
DR PIR; A03827; WMAD67.
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: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: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 InterPro; IPR014410; Aden_E1A.
DR Pfam; PF02703; Adeno_E1A; 1.
DR PIRSF; PIRSF003669; Aden_E1A; 1.
PE 3: Inferred from homology;
KW Activator; Alternative splicing; Early protein;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host nucleus;
KW Host-virus interaction; 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; Transcription;
KW Transcription regulation; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..261
FT /note="Early E1A protein"
FT /id="PRO_0000221695"
FT ZN_FING 163..183
FT /evidence="ECO:0000250|UniProtKB:P03254"
FT REGION 43..51
FT /note="Interaction with RB1 in competition with E2F1"
FT /evidence="ECO:0000250"
FT REGION 78..149
FT /note="Interaction with UBE2I"
FT /evidence="ECO:0000250"
FT REGION 197..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 106..110
FT /note="PXLXP motif, interaction with host ZMYND11"
FT /evidence="ECO:0000250"
FT MOTIF 115..119
FT /note="LXCXE motif, interaction with host RB1 and
FT TMEM173/STING"
FT /evidence="ECO:0000255"
FT MOTIF 250..254
FT /note="PXDLS motif, CTBP-binding"
FT /evidence="ECO:0000250"
FT MOTIF 256..261
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 199..214
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 232..246
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 26..57
FT /note="NTLMGDDPEPPVQPFDPPTLHDLYDLEVDGPE -> LCLMMSHLLLIQLPHL
FT LKFRRPHLQTYASPFL (in isoform early E1A 6.3 kDa protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_028920"
FT VAR_SEQ 58..261
FT /note="Missing (in isoform early E1A 6.3 kDa protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_028921"
FT VAR_SEQ 164..194
FT /note="Missing (in isoform early E1A 24 kDa protein)"
FT /evidence="ECO:0000305"
FT /id="VSP_000199"
FT VARIANT 62
FT /note="G -> E (in strain: Grider)"
FT VARIANT 202
FT /note="P -> G (in strain: Grider)"
SQ SEQUENCE 261 AA; 28385 MW; 770E327BD524A06C CRC64;
MRHLRFLPQE IISSETGIEI LEFVVNTLMG DDPEPPVQPF DPPTLHDLYD LEVDGPEDPN
EGAVNGFFTD SMLLAADEGL DINPPPETLV TPGVVVESGR GGKKLPDLGA AEMDLRCYEE
GFPPSDDEDG ETEQSIHTAV NEGVKAASDV FKLDCPELPG HGCKSCEFHR NNTGMKELLC
SLCYMRMHCH FIYSPVSDDE SPSPDSTTSP PEIQAPAPAN VCKPIPVKPK PGKRPAVDKL
EDLLEGGDGP LDLSTRKLPR Q
