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Protein

Early E1A protein

Gene
N/A
Organism
Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E1A protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes and of the E2 region of the adenoviral genome. Release of E2F1 leads to the ARF-mediated inhibition of MDM2 and causes TP53/p53 to accumulate because it is not targeted for degradation by MDM2-mediated ubiquitination anymore. This increase in TP53, in turn, would arrest the cell proliferation and direct its death but this effect is counteracted by the viral protein E1B-55K. Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. Interaction with RBX1 and CUL1 inhibits ubiquitination of the proteins targeted by SCF(FBXW7) ubiquitin ligase complex, and may be linked to unregulated host cell proliferation. The tumorigenesis-restraining activity of E1A may be related to the disruption of the host CtBP-CtIP complex through the CtBP binding motif. Interacts with host TBP protein; this interaction probably disrupts the TBP-TATA complex.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri154 – 17421By similarityAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Eukaryotic host gene expression shutoff by virus, Eukaryotic host transcription shutoff by virus, G1/S host cell cycle checkpoint dysregulation by virus, Host gene expression shutoff by virus, Host-virus interaction, Inhibition of eukaryotic host transcription initiation by virus, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host STAT1 by virus, Modulation of host cell cycle by virus, Modulation of host E3 ubiquitin ligases by virus, Modulation of host ubiquitin pathway by virus, Transcription, Transcription regulation, Viral immunoevasion

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Early E1A proteinCurated
Alternative name(s):
Early E1A 32 kDa protein
OrganismiHuman adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2)
Taxonomic identifieri10515 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageAdenoviridaeMastadenovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000008167 Componenti: Genome

Subcellular locationi

  • Host nucleus By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi157 – 1571C → S: Abolishes ATF7-mediated transcriptional activation. 1 Publication
Mutagenesisi178 – 1781T → P: No effect on ATF7-mediated transcriptional activation. 1 Publication
Mutagenesisi185 – 1851S → R: Abolishes ATF7-mediated transcriptional activation. 1 Publication

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 289289Early E1A proteinPRO_0000221692Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei89 – 891Phosphoserine; by hostBy similarity
Modified residuei219 – 2191Phosphoserine; by hostBy similarity
Modified residuei231 – 2311Phosphoserine; by hostBy similarity

Keywords - PTMi

Phosphoprotein

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Interacts with host UBE2I; this interaction interferes with polySUMOylation. Interacts with host RB1; this interaction induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting the activity of RB1 and activating E2F1-regulated genes. Interacts with host ATF7; the interaction enhances ATF7-mediated viral transactivation activity which requires the zinc binding domains of both proteins. Isoform early E1A 32 kDa protein and isoform early E1A 26 kDa protein interact (via N-terminus) with CUL1 and E3 ubiquitin ligase RBX1; these interactions inhibit RBX1-CUL1-dependent elongation reaction of ubiquitin chains and attenuate ubiquitination of SCF(FBXW7) target proteins. Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc finger); this interaction inhibits E1A mediated transactivation. Interacts with host EP300; this interaction stimulates the acetylation of RB1 by recruiting EP300 and RB1 into a multimeric-protein complex. Interacts with host CTBP1 and CTBP2; this interaction seems to potentiate viral replication. Interacts with host DCAF7. Interacts with host DYRK1A. Interacts with host KPNA4; this interaction allows E1A import into the host nucleus. Interacts with host EP400; this interaction stabilizes MYC.By similarity

Protein-protein interaction databases

DIPiDIP-570N.
IntActiP03254. 1 interaction.
MINTiMINT-198575.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni41 – 499Interaction with RB1 in competition with E2F1By similarity
Regioni76 – 14065Interaction with UBE2IBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi113 – 1175PXLXP motif, interaction with host ZMYND11By similarity
Motifi122 – 1265LXCXE motif, interaction with host RB1Sequence analysis
Motifi258 – 28932Bipartite nuclear localization signalSequence analysisBy similarityAdd
BLAST
Motifi279 – 2835PXDLS motif, CTBP-bindingBy similarity

Sequence similaritiesi

Belongs to the adenoviridae E1A protein family.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri154 – 17421By similarityAdd
BLAST

Keywords - Domaini

Zinc-finger

Family and domain databases

InterProiIPR014410. Aden_E1A.
[Graphical view]
PfamiPF02703. Adeno_E1A. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoforms are derived from the E1 region of the genome.

Isoform early E1A 32 kDa protein (identifier: P03254-1) [UniParc]FASTAAdd to basket

Also known as: 289R, L-E1A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD
60 70 80 90 100
VTAPEDPNEE AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE
110 120 130 140 150
QPEQRALGPV SMPNLVPEVI DLTCHEAGFP PSDDEDEEGE EFVLDYVEHP
160 170 180 190 200
GHGCRSCHYH RRNTGDPDIM CSLCYMRTCG MFVYSPVSEP EPEPEPEPEP
210 220 230 240 250
ARPTRRPKLV PAILRRPTSP VSRECNSSTD SCDSGPSNTP PEIHPVVPLC
260 270 280
PIKPVAVRVG GRRQAVECIE DLLNESGQPL DLSCKRPRP
Length:289
Mass (Da):31,851
Last modified:July 21, 1986 - v1
Checksum:i4264747DAD74FFC5
GO
Isoform early E1A 26 kDa protein (identifier: P03254-2) [UniParc]FASTAAdd to basket

Also known as: 243R, S-E1A

The sequence of this isoform differs from the canonical sequence as follows:
     140-185: Missing.

Show »
Length:243
Mass (Da):26,452
Checksum:i0408B45F94D2F250
GO
Isoform early E1A 6 kDa protein (identifier: P03254-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     29-55: ADNLPPPSHFEPPTLHELYDLDVTAPE → CLNLSLSPSQNRSLQDLPGVLNWCLLS
     56-289: Missing.

Show »
Length:55
Mass (Da):6,075
Checksum:i078B55A060462F3A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 681D → E in AAA92197 (PubMed:7142161).Curated
Sequence conflicti68 – 681D → E in AAA92199 (PubMed:7142161).Curated
Sequence conflicti81 – 811L → F in AAA92197 (PubMed:7142161).Curated
Sequence conflicti81 – 811L → F in AAA92199 (PubMed:7142161).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei29 – 5527ADNLP…VTAPE → CLNLSLSPSQNRSLQDLPGV LNWCLLS in isoform early E1A 6 kDa protein. CuratedVSP_028916Add
BLAST
Alternative sequencei56 – 289234Missing in isoform early E1A 6 kDa protein. CuratedVSP_028917Add
BLAST
Alternative sequencei140 – 18546Missing in isoform early E1A 26 kDa protein. CuratedVSP_000197Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J01917 Genomic DNA. Translation: AAA92197.1.
J01917 Genomic DNA. Translation: AAA92198.1.
J01917 Genomic DNA. Translation: AAA92199.1.
PIRiA03824. Q2AD2.
RefSeqiAP_000161.1. AC_000007.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J01917 Genomic DNA. Translation: AAA92197.1.
J01917 Genomic DNA. Translation: AAA92198.1.
J01917 Genomic DNA. Translation: AAA92199.1.
PIRiA03824. Q2AD2.
RefSeqiAP_000161.1. AC_000007.1.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-570N.
IntActiP03254. 1 interaction.
MINTiMINT-198575.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

InterProiIPR014410. Aden_E1A.
[Graphical view]
PfamiPF02703. Adeno_E1A. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Structure of two spliced mRNAs from the transforming region of human subgroup C adenoviruses."
    Perricaudet M., Akusjaervi G., Virtanen A., Pettersson U.
    Nature 281:694-696(1979) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS EARLY E1A 32 KDA PROTEIN AND EARLY E1A 26 KDA PROTEIN).
  2. "Nucleotide sequences from the adenovirus-2 genome."
    Gingeras T.R., Sciaky D., Gelinas R.E., Bing-Dong J., Yen C.E., Kelly M.M., Bullock P.A., Parsons B.L., O'Neill K.E., Roberts R.J.
    J. Biol. Chem. 257:13475-13491(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS EARLY E1A 32 KDA PROTEIN; EARLY E1A 26 KDA PROTEIN AND EARLY E1A 6 KDA PROTEIN).
  3. "Transcriptional activation by the adenovirus larger E1a product is mediated by members of the cellular transcription factor ATF family which can directly associate with E1a."
    Chatton B., Bocco J.L., Gaire M., Hauss C., Reimund B., Goetz J., Kedinger C.
    Mol. Cell. Biol. 13:561-570(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST ATF7, MUTAGENESIS OF CYS-157; THR-178 AND SER-185.

Entry informationi

Entry nameiE1A_ADE02
AccessioniPrimary (citable) accession number: P03254
Secondary accession number(s): P24934, Q67788
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: May 11, 2016
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.