E1A_ADEC2
ID E1A_ADEC2 Reviewed; 171 AA.
AC P35981;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 23-FEB-2022, entry version 53.
DE RecName: Full=Early E1A protein;
DE AltName: Full=Early E1A 20 kDa protein;
OS Canine adenovirus serotype 2 (CAdV-2) (Canine adenovirus 2).
OC Viruses; Varidnaviria; Bamfordvirae; Preplasmiviricota; Tectiliviricetes;
OC Rowavirales; Adenoviridae; Mastadenovirus; Canine mastadenovirus A.
OX NCBI_TaxID=10514;
OH NCBI_TaxID=9615; Canis lupus familiaris (Dog) (Canis familiaris).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2623943; DOI=10.1016/0168-1702(89)90005-1;
RA Spibey N., McClory R.S., Cavanagh H.M.A.;
RT "Identification and nucleotide sequence of the early region 1 from canine
RT adenovirus types 1 and 2.";
RL Virus Res. 14:241-256(1989).
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. {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.
CC {ECO:0000250|UniProtKB:P03254, ECO:0000250|UniProtKB:P03255}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:P03255}.
CC -!- SIMILARITY: Belongs to the adenoviridae E1A protein family.
CC {ECO:0000305}.
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DR PIR; B60010; B60010.
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: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 PIRSF; PIRSF003669; Aden_E1A; 1.
PE 3: Inferred from homology;
KW Activator; 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; Transcription;
KW Transcription regulation; Viral immunoevasion; Zinc; Zinc-finger.
FT CHAIN 1..171
FT /note="Early E1A protein"
FT /id="PRO_0000221703"
FT ZN_FING 145..163
FT /evidence="ECO:0000250|UniProtKB:P03254"
FT REGION 40..48
FT /note="Interaction with RB1 in competition with E2F1"
FT /evidence="ECO:0000250"
FT REGION 67..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 106..110
FT /note="LXCXE motif, interaction with host RB1"
FT /evidence="ECO:0000255"
FT MOTIF 166..171
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 67..84
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 171 AA; 18942 MW; 2527EC1338062FB0 CRC64;
MKYTIVPAPR NLHDYVLELL EEWHPDCLDC EYPNGSPSPP TLHDLFDVEL ETSHPFVGLC
DSCAEADTDS SASTEGDSGF SPLSTPPVSP IPPHPTSPAS ISDDMLLCLE EMPTFDDEDE
VRSAATTFER WENTFDPHVG PIFGCLRCAF YQEQDDNALC GLCYPKGPCR R
