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Protein

Early E1A protein

Gene
N/A
Organism
Human adenovirus A serotype 12 (HAdV-12) (Human adenovirus 12)
Status
Reviewed-Annotation score: Annotation score: 5 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.By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri159 – 17921By similarityAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host NF-kappa-B 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 protein
Alternative name(s):
Early E1A 29.5 kDa protein
OrganismiHuman adenovirus A serotype 12 (HAdV-12) (Human adenovirus 12)
Taxonomic identifieri28282 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageAdenoviridaeMastadenovirusHuman mastadenovirus A
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000004993 Componenti: Genome

Subcellular locationi

  • Host nucleus By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 266266Early E1A proteinPRO_0000221696Add
BLAST

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. Interacts with host TBP protein; this interaction probably disrupts the TBP-TATA complex.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ATF1P188462EBI-7225021,EBI-852794From a different organism.
Cdkn1bO087692EBI-6947456,EBI-7796656From a different organism.
CREB1P162202EBI-7225021,EBI-711855From a different organism.
CREBBPQ927935EBI-6947456,EBI-81215From a different organism.
EP300Q094723EBI-6947456,EBI-447295From a different organism.
POU5F1Q018602EBI-6947456,EBI-475687From a different organism.
PRKAR1AP106445EBI-7225021,EBI-476431From a different organism.
PRKAR2AP138615EBI-7225021,EBI-2556122From a different organism.
YY1P254903EBI-6947456,EBI-765538From a different organism.

Protein-protein interaction databases

IntActiP03259. 12 interactions.
MINTiMINT-1785129.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni39 – 479Interaction with RB1 in competition with E2F1By similarity
Regioni75 – 14571Interaction with UBE2IAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi98 – 1025PXLXP motif, interaction with host ZMYND11By similarity
Motifi107 – 1115LXCXE motif, interaction with host RB1Sequence analysis
Motifi255 – 2595PXDLS motif, CTBP-bindingBy similarity
Motifi261 – 2655Nuclear localization signalSequence analysis

Sequence similaritiesi

Belongs to the adenoviridae E1A protein family.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri159 – 17921By similarityAdd
BLAST

Keywords - Domaini

Zinc-finger

Family and domain databases

InterProiIPR014410. Aden_E1A.
[Graphical view]
PfamiPF02703. Adeno_E1A. 2 hits.
[Graphical view]
PIRSFiPIRSF003669. Aden_E1A. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Early E1A 29.5 kDa protein (identifier: P03259-1) [UniParc]FASTAAdd to basket

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
MRTEMTPLVL SYQEADDILE HLVDNFFNEV PSDDDLYVPS LYELYDLDVE
60 70 80 90 100
SAGEDNNEQA VNEFFPESLI LAASEGLFLP EPPVLSPVCE PIGGECMPQL
110 120 130 140 150
HPEDMDLLCY EMGFPCSDSE DEQDENGMAH VSASAAAAAA DREREEFQLD
160 170 180 190 200
HPELPGHNCK SCEHHRNSTG NTDLMCSLCY LRAYNMFIYS PVSDNEPEPN
210 220 230 240 250
STLDGDERPS PPKLGSAVPE GVIKPVPQRV TGRRRCAVES ILDLIQEEER
260
EQTVPVDLSV KRPRCN
Length:266
Mass (Da):29,691
Last modified:July 21, 1986 - v1
Checksum:iA93A93A62D4541BE
GO
Isoform Early E1A 26 kDa protein (identifier: P03259-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     160-190: Missing.

Show »
Length:235
Mass (Da):26,050
Checksum:i676F452FA17EB3CA
GO
Isoform Early E1A 22 kDa protein (identifier: P03259-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     191-234: Missing.
     259-266: SVKRPRCN → KCAMGGGR

Show »
Length:222
Mass (Da):24,853
Checksum:i01DD89B8B01D8246
GO
Isoform Early E1A 6 kDa protein (identifier: P03259-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     31-244: Missing.
     245-266: IQEEEREQTVPVDLSVKRPRCN → FPIMSLNLIALWMAMSDPHPRN

Show »
Length:52
Mass (Da):6,107
Checksum:i68D6E5EE080ED5CC
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei31 – 244214Missing in isoform Early E1A 6 kDa protein. CuratedVSP_000200Add
BLAST
Alternative sequencei160 – 19031Missing in isoform Early E1A 26 kDa protein. CuratedVSP_000201Add
BLAST
Alternative sequencei191 – 23444Missing in isoform Early E1A 22 kDa protein. CuratedVSP_000202Add
BLAST
Alternative sequencei245 – 26622IQEEE…RPRCN → FPIMSLNLIALWMAMSDPHP RN in isoform Early E1A 6 kDa protein. CuratedVSP_000203Add
BLAST
Alternative sequencei259 – 2668SVKRPRCN → KCAMGGGR in isoform Early E1A 22 kDa protein. CuratedVSP_000204

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00004 Genomic DNA. Translation: CAA23400.1.
V00004 Genomic DNA. Translation: CAA23401.1.
V00004 Genomic DNA. Translation: CAA23402.1.
X73487 Genomic DNA. Translation: CAA51877.1.
PIRiA03828. AQADG2.
RefSeqiNP_040910.2. NC_001460.1.

Genome annotation databases

GeneIDi1460853.
KEGGivg:1460853.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00004 Genomic DNA. Translation: CAA23400.1.
V00004 Genomic DNA. Translation: CAA23401.1.
V00004 Genomic DNA. Translation: CAA23402.1.
X73487 Genomic DNA. Translation: CAA51877.1.
PIRiA03828. AQADG2.
RefSeqiNP_040910.2. NC_001460.1.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP03259. 12 interactions.
MINTiMINT-1785129.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1460853.
KEGGivg:1460853.

Family and domain databases

InterProiIPR014410. Aden_E1A.
[Graphical view]
PfamiPF02703. Adeno_E1A. 2 hits.
[Graphical view]
PIRSFiPIRSF003669. Aden_E1A. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structure and gene organization in the transformed Hind III-G fragment of Ad12."
    Sugisaki H., Sugimoto K., Takanami M., Shiroki K., Saito I., Shimojo H., Sawada Y., Uemizu Y., Uesugi S., Fujinaga K.
    Cell 20:777-786(1980) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Structure of two adenovirus type 12 transforming polypeptides and their evolutionary implications."
    Perricaudet M., le Moullec J.-M., Tiollais P., Pettersson U.
    Nature 288:174-176(1980) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Nucleotide sequence of human adenovirus type 12 DNA: comparative functional analysis."
    Sprengel J., Schmitz B., Heuss-Neitzel D., Zock C., Doerfler W.
    J. Virol. 68:379-389(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "mUBC9, a novel adenovirus E1A-interacting protein that complements a yeast cell cycle defect."
    Hateboer G., Hijmans E.M., Nooij J.B.D., Schlenker S., Jentsch S., Bernards R.
    J. Biol. Chem. 271:25906-25911(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH UBE2I.

Entry informationi

Entry nameiE1A_ADE12
AccessioniPrimary (citable) accession number: P03259
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 14, 2015
This is version 79 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

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.