UniProtKB - P03255 (E1A_ADE05)
Early E1A protein
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. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:26405230).
Promotes the sumoylation of host ZBED1/hDREF with SUMO1 (PubMed:25210186).
1 Publication6 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 154 – 174 | 2 PublicationsAdd BLAST | 21 |
GO - Molecular functioni
- DNA-binding transcription factor binding Source: CAFA
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
- modulation by virus of host protein ubiquitination Source: UniProtKB-KW
- modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-KW
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of protein sumoylation Source: UniProtKB
- regulation by virus of viral protein levels in host cell Source: UniProtKB
- regulation of protein localization Source: UniProtKB
- regulation of transcription, DNA-templated Source: InterPro
- suppression by virus of host gene expression Source: UniProtKB-KW
- suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity Source: UniProtKB-KW
- suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
Keywordsi
Names & Taxonomyi
Protein namesi | Recommended name: Early E1A proteinAlternative name(s): Early E1A 32 kDa protein |
Organismi | Human adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5) |
Taxonomic identifieri | 28285 [NCBI] |
Taxonomic lineagei | Viruses › Varidnaviria › Bamfordvirae › Preplasmiviricota › Tectiliviricetes › Rowavirales › Adenoviridae › Mastadenovirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 115 | L → A: Complete loss of interaction with host ZMYND11. 1 Publication | 1 | |
Mutagenesisi | 122 – 126 | LTCHE → VTSHD: Abolishes interaction with host TMEM173/STING. 1 Publication | 5 | |
Mutagenesisi | 122 | L → I: Abolishes binding to UBE2I. 1 Publication | 1 | |
Mutagenesisi | 123 | T → H: Abolishes increased sumoylation of human ZBED1. 1 Publication | 1 | |
Mutagenesisi | 154 | C → S: Loss of transactivation. 1 Publication | 1 | |
Mutagenesisi | 157 | C → S: Loss of transactivation. 1 Publication | 1 | |
Mutagenesisi | 171 | C → S: Loss of transactivation. 1 Publication | 1 | |
Mutagenesisi | 174 | C → S: Loss of transactivation. 1 Publication | 1 | |
Mutagenesisi | 253 | K → E: Reduces interaction with human ZBED1. 1 Publication | 1 | |
Mutagenesisi | 262 – 263 | RR → EE: Reduces interaction with human ZBED1. 1 Publication | 2 | |
Mutagenesisi | 267 | E → K: Reduces interaction with human ZBED1. 1 Publication | 1 | |
Mutagenesisi | 272 – 273 | LL → AA: Abolishes interaction with human ZBED1. Abolishes E1A-mediated increased sumoylation of ZBED1. Abolishes localization of ZBED1 to peripheral areas of PML bodies. 1 Publication | 2 | |
Mutagenesisi | 281 – 282 | DL → AS: 30% decrease in virus replication efficiency. Enhanced immortalization and Ras cooperative transformation. 1 Publication | 2 |
Keywords - Diseasei
OncogenePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000221694 | 1 – 289 | Early E1A proteinAdd BLAST | 289 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 89 | Phosphoserine; by host1 Publication | 1 | |
Modified residuei | 219 | Phosphoserine; by host1 Publication | 1 | |
Modified residuei | 231 | Phosphoserine; by host1 Publication | 1 |
Keywords - PTMi
PhosphoproteinPTM databases
iPTMneti | P03255 |
Interactioni
Subunit structurei
Interacts with host UBE2I; this interaction interferes with polySUMOylation (Probable) (PubMed:8824223, PubMed:20543865).
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 (PubMed:17974914).
Interacts with host ATF7; the interaction enhances ATF7-mediated viral transactivation activity which requires the zinc binding domains of both proteins (By similarity). 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 (PubMed:19679664).
Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc finger); this interaction inhibits E1A mediated transactivation (PubMed:11733528).
Interacts with host EP300; this interaction stimulates the acetylation of RB1 by recruiting EP300 and RB1 into a multimeric-protein complex (PubMed:11433299).
Interacts with host CTBP1 and CTBP2; this interaction seems to potentiate viral replication (PubMed:23747199, PubMed:7479821).
Interacts with host DCAF7 (ref.16).
Interacts with host DYRK1A (PubMed:23864635).
Interacts with host KPNA4; this interaction allows E1A import into the host nucleus (PubMed:23864635).
Interacts with host EP400; this interaction stabilizes MYC (PubMed:18413597).
Interacts with host TBP protein; this interaction probably disrupts the TBP-TATA complex (PubMed:8146144).
Interacts (via LXCXE motif) with host TMEM173/STING; this interaction impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:26405230).
Interacts (via C-terminus) with host ZBED1/hDREF (via C-terminus); the interaction is direct (PubMed:25210186).
By similarityCurated13 PublicationsBinary interactionsi
P03255
Isoform early E1A 32 kDa protein [P03255-1]
Isoform early E1A 26 kDa protein [P03255-2]
GO - Molecular functioni
- DNA-binding transcription factor binding Source: CAFA
Protein-protein interaction databases
DIPi | DIP-40736N |
ELMi | P03255 |
IntActi | P03255, 38 interactors |
MINTi | P03255 |
Structurei
Secondary structure
3D structure databases
BMRBi | P03255 |
SMRi | P03255 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P03255 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 41 – 49 | Interaction with RB1 in competition with E2F1Curated | 9 | |
Regioni | 76 – 140 | Interaction with UBE2IAdd BLAST | 65 | |
Regioni | 82 – 107 | DisorderedSequence analysisAdd BLAST | 26 | |
Regioni | 186 – 240 | DisorderedSequence analysisAdd BLAST | 55 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 113 – 117 | PXLXP motif, interaction with host ZMYND11 | 5 | |
Motifi | 122 – 126 | LXCXE motif, interaction with host RB1 and TMEM173/STINGSequence analysis1 Publication | 5 | |
Motifi | 258 – 289 | Bipartite nuclear localization signalSequence analysis1 PublicationAdd BLAST | 32 | |
Motifi | 279 – 283 | PXDLS motif, CTBP-binding1 Publication | 5 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 220 – 238 | Polar residuesSequence analysisAdd BLAST | 19 |
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 154 – 174 | 2 PublicationsAdd BLAST | 21 |
Keywords - Domaini
Zinc-fingerFamily and domain databases
DisProti | DP01150 |
IDEALi | IID90003 |
InterProi | View protein in InterPro IPR014410, Aden_E1A |
Pfami | View protein in Pfam PF02703, Adeno_E1A, 1 hit |
PIRSFi | PIRSF003669, Aden_E1A, 1 hit |
s (3)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
ARPTRRPKMA PAILRRPTSP VSRECNSSTD SCDSGPSNTP PEIHPVVPLC
260 270 280
PIKPVAVRVG GRRQAVECIE DLLNEPGQPL DLSCKRPRP
The sequence of this isoform differs from the canonical sequence as follows:
140-185: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
29-55: ADNLPPPSHFEPPTLHELYDLDVTAPE → CLNLSLSPSQNRSLQDLPAVLKWRLLS
56-289: Missing.
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_028918 | 29 – 55 | ADNLP…VTAPE → CLNLSLSPSQNRSLQDLPAV LKWRLLS in isoform early E1A 6 kDa protein. CuratedAdd BLAST | 27 | |
Alternative sequenceiVSP_028919 | 56 – 289 | Missing in isoform early E1A 6 kDa protein. CuratedAdd BLAST | 234 | |
Alternative sequenceiVSP_000198 | 140 – 185 | Missing in isoform early E1A 26 kDa protein. CuratedAdd BLAST | 46 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M73260 Genomic DNA No translation available. X02996 Genomic DNA Translation: CAB40663.1 X02996 Genomic DNA Translation: CAB40664.1 X02996 Genomic DNA Translation: CAB40665.1 |
PIRi | A03825, ERAD65 C03824, Q2AD5 |
RefSeqi | AP_000197.1, AC_000008.1 [P03255-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M73260 Genomic DNA No translation available. X02996 Genomic DNA Translation: CAB40663.1 X02996 Genomic DNA Translation: CAB40664.1 X02996 Genomic DNA Translation: CAB40665.1 |
PIRi | A03825, ERAD65 C03824, Q2AD5 |
RefSeqi | AP_000197.1, AC_000008.1 [P03255-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2KJE | NMR | - | B | 53-91 | [»] | |
2R7G | X-ray | 1.67 | B/D/E | 40-49 | [»] | |
6H6D | X-ray | 2.40 | C/F | 234-243 | [»] | |
6H6H | X-ray | 2.40 | C/F | 234-243 | [»] | |
BMRBi | P03255 | |||||
SMRi | P03255 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
DIPi | DIP-40736N |
ELMi | P03255 |
IntActi | P03255, 38 interactors |
MINTi | P03255 |
PTM databases
iPTMneti | P03255 |
Miscellaneous databases
EvolutionaryTracei | P03255 |
Family and domain databases
DisProti | DP01150 |
IDEALi | IID90003 |
InterProi | View protein in InterPro IPR014410, Aden_E1A |
Pfami | View protein in Pfam PF02703, Adeno_E1A, 1 hit |
PIRSFi | PIRSF003669, Aden_E1A, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | E1A_ADE05 | |
Accessioni | P03255Primary (citable) accession number: P03255 Secondary accession number(s): P06438, Q64825, Q64826 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | July 21, 1986 | |
Last modified: | May 25, 2022 | |
This is version 159 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families