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P03255 (E1A_ADE05) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Early E1A 32 kDa protein
OrganismHuman adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5) [Complete proteome]
Taxonomic identifier28285 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stageAdenoviridaeMastadenovirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E1A protein has both transforming and trans-activating activities. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Disrupts the function of host retinoblastoma protein RB1/pRb and isoform earlyE1A 26 kDa protein stabilizes TP53, which are key regulators of the cell cycle. Induces the disassembly of the E2F1 transcription factors from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. 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. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. 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. Ref.6 Ref.8 Ref.9 Ref.10

Subunit structure

Interacts with host UBE2I; this interaction interferes with polySUMOylation Probable. Interaction with host RB1 induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting RB1's activity. Interacts with host ATF7; the interaction enhances ATF7-mediated viral transactivation activity which requires the zinc binding domains of both proteins By similarity. Isoform earlyE1A 32 kDa protein and isoform earlyE1A 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. Interacts (via N-terminus) with the SCF(FBXW7) complex; this interaction results in inhibition of the ubiquitin ligase activity of the SCF(FBXW7) complex, ubiquitination of SCF(FBXW7) target proteins being diminished. Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc finger); this interaction inhibits E1A mediated transactivation. Ref.5 Ref.7 Ref.9 Ref.10

Subcellular location

Host nucleus Potential.

Sequence similarities

Belongs to the adenoviridae E1A protein family.

Ontologies

Keywords
   Biological processEukaryotic 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
   Cellular componentHost nucleus
   Coding sequence diversityAlternative splicing
   Developmental stageEarly protein
   DiseaseOncogene
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological_processmodulation by virus of host G1/S transition checkpoint

Inferred from electronic annotation. Source: UniProtKB-KW

modulation by virus of host ubiquitin-protein ligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of cell proliferation

Inferred from direct assay PubMed 9054499. Source: BHF-UCL

suppression by virus of host STAT1 activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host transcription initiation from RNA polymerase II promoter

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 10330164PubMed 10347196PubMed 10734313PubMed 10779361Ref.7PubMed 12743606PubMed 1331501PubMed 16763564PubMed 19249677PubMed 7565739PubMed 7565781PubMed 9018065PubMed 9675118PubMed 9687513PubMed 16763564PubMed 9881977PubMed 10330164PubMed 12743606PubMed 15604276PubMed 16763564PubMed 9687513PubMed 9881977. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Cdkn1bO087692EBI-2603114,EBI-7796656From a different organism.
CREBBPQ927933EBI-2603114,EBI-81215From a different organism.
EP300Q094723EBI-6859460,EBI-447295From a different organism.
KAT2BQ928313EBI-2603114,EBI-477430From a different organism.
MDM4O151513EBI-6859460,EBI-398437From a different organism.
MED28Q9H2042EBI-2603114,EBI-514199From a different organism.
PSMC3P179802EBI-6692439,EBI-359720From a different organism.
PSMC5P621952EBI-6692439,EBI-357745From a different organism.
RARBP10826-22EBI-2603114,EBI-8583223From a different organism.
RB1P064008EBI-2603114,EBI-491274From a different organism.
RBL1P287493EBI-2603114,EBI-971402From a different organism.
RBL2Q089992EBI-2603114,EBI-971439From a different organism.
STAT1P422242EBI-6692439,EBI-1057697From a different organism.
TAF1P216753EBI-2603114,EBI-491289From a different organism.
Taf4P478253EBI-2603114,EBI-277958From a different organism.
ZMYND11Q153263EBI-2603114,EBI-2623509From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Isoforms are derived from the E1 region of the genome.
Isoform early E1A 32 kDa protein (identifier: P03255-1)

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.
Isoform early E1A 26 kDa protein (identifier: P03255-2)

The sequence of this isoform differs from the canonical sequence as follows:
     140-185: Missing.
Note: No experimental confirmation available.
Isoform early E1A 6 kDa protein (identifier: P03255-3)

The sequence of this isoform differs from the canonical sequence as follows:
     29-55: ADNLPPPSHFEPPTLHELYDLDVTAPE → CLNLSLSPSQNRSLQDLPAVLKWRLLS
     56-289: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 289289Early E1A 32 kDa protein
PRO_0000221694

Regions

Zinc finger154 – 17421 Potential
Region41 – 499Interaction with RB1 in competition with E2F1 Probable
Region76 – 14065Interaction with UBE2I
Motif113 – 1175PXLXP motif, interaction with host ZMYND11
Motif122 – 1265LXCXE motif, interaction with host RB1 Potential
Motif279 – 2835PXDLS motif, CTBP-binding
Motif285 – 2895Nuclear localization signal Potential

Amino acid modifications

Modified residue891Phosphoserine; by host Ref.3
Modified residue2191Phosphoserine; by host Ref.3
Modified residue2311Phosphoserine; by host Ref.3

Natural variations

Alternative sequence29 – 5527ADNLP…VTAPE → CLNLSLSPSQNRSLQDLPAV LKWRLLS in isoform early E1A 6 kDa protein.
VSP_028918
Alternative sequence56 – 289234Missing in isoform early E1A 6 kDa protein.
VSP_028919
Alternative sequence140 – 18546Missing in isoform early E1A 26 kDa protein.
VSP_000198

Experimental info

Mutagenesis1151L → A: Complete loss of interaction with host ZMYND11. Ref.7
Mutagenesis1221L → I: Abolishes binding to UBE2I. Ref.5
Mutagenesis1541C → S: Loss of transactivation. Ref.4
Mutagenesis1571C → S: Loss of transactivation. Ref.4
Mutagenesis1711C → S: Loss of transactivation. Ref.4
Mutagenesis1741C → S: Loss of transactivation. Ref.4

Secondary structure

........... 289
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform early E1A 32 kDa protein [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 8C5997A3908C40D7

FASTA28931,851
        10         20         30         40         50         60 
MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD VTAPEDPNEE 

        70         80         90        100        110        120 
AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE QPEQRALGPV SMPNLVPEVI 

       130        140        150        160        170        180 
DLTCHEAGFP PSDDEDEEGE EFVLDYVEHP GHGCRSCHYH RRNTGDPDIM CSLCYMRTCG 

       190        200        210        220        230        240 
MFVYSPVSEP EPEPEPEPEP ARPTRRPKMA PAILRRPTSP VSRECNSSTD SCDSGPSNTP 

       250        260        270        280 
PEIHPVVPLC PIKPVAVRVG GRRQAVECIE DLLNEPGQPL DLSCKRPRP 

« Hide

Isoform early E1A 26 kDa protein [UniParc].

Checksum: CA355781A92A4D42
Show »

FASTA24326,452
Isoform early E1A 6 kDa protein [UniParc].

Checksum: 001555BAD0415F3A
Show »

FASTA556,156

References

[1]"The nucleotide sequence of the transforming early region E1 of adenovirus type 5 DNA."
van Ormondt H., Maat J., van Beveren C.P.
Gene 11:299-309(1980) [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).
[2]"The sequence of the genome of adenovirus type 5 and its comparison with the genome of adenovirus type 2."
Chroboczek J., Bieber F., Jacrot B.
Virology 186:280-285(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Identification of the phosphorylation sites in early region 1A proteins of adenovirus type 5 by amino acid sequencing of peptide fragments."
Tremblay M.L., McGlade C.J., Gerber G.E., Branton P.E.
J. Biol. Chem. 263:6375-6383(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-89; SER-219 AND SER-231.
[4]"Conversion of the E1A Cys4 zinc finger to a nonfunctional His2,Cys2 zinc finger by a single point mutation."
Webster L.C., Zhang K., Chance B., Ayene I., Culp J.S., Huang W.-J., Wu F.Y.-H., Ricciardi R.P.
Proc. Natl. Acad. Sci. U.S.A. 88:9989-9993(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-154; CYS-157; CYS-171 AND CYS-174.
[5]"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 HUMAN UBE2I, MUTAGENESIS OF LEU-122.
[6]"Stabilization of p53 by adenovirus E1A occurs through its amino-terminal region by modification of the ubiquitin-proteasome pathway."
Nakajima T., Morita K., Tsunoda H., Imajoh-Ohmi S., Tanaka H., Yasuda H., Oda K.
J. Biol. Chem. 273:20036-20045(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION OF ISOFORM EARLY E1A 26 KDA PROTEIN.
[7]"The conserved Mynd domain of BS69 binds cellular and oncoviral proteins through a common PXLXP motif."
Ansieau S., Leutz A.
J. Biol. Chem. 277:4906-4910(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN ZMYND11/BS69, MUTAGENESIS OF LEU-115.
[8]"Viral oncoproteins E1A and E7 and cellular LxCxE proteins repress SUMO modification of the retinoblastoma tumor suppressor."
Ledl A., Schmidt D., Muller S.
Oncogene 24:3810-3818(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Adenovirus E1A inhibits SCF(Fbw7) ubiquitin ligase."
Isobe T., Hattori T., Kitagawa K., Uchida C., Kotake Y., Kosugi I., Oda T., Kitagawa M.
J. Biol. Chem. 284:27766-27779(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST RBX1 AND HOST CUL1, INTERACTION WITH SCF(FBXW7) COMPLEX.
[10]"Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation."
Yousef A.F., Fonseca G.J., Pelka P., Ablack J.N., Walsh C., Dick F.A., Bazett-Jones D.P., Shaw G.S., Mymryk J.S.
Oncogene 29:4693-4704(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST UBE2I.
[11]"Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor."
Liu X., Marmorstein R.
Genes Dev. 21:2711-2716(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 40-49 IN COMPLEX WITH HUMAN RB1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M73260 Genomic DNA. No translation available.
X02996 Genomic DNA. Translation: CAB40663.1.
X02996 Genomic DNA. Translation: CAB40664.1.
X02996 Genomic DNA. Translation: CAB40665.1.
PIRERAD65. A03825.
Q2AD5. C03824.
RefSeqAP_000197.1. AC_000008.1. [P03255-1]

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KJENMR-B53-91[»]
2R7GX-ray1.67B/D/E40-49[»]
ProteinModelPortalP03255.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-40736N.
IntActP03255. 33 interactions.
MINTMINT-87547.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR014410. Aden_E1A.
IPR003853. Adeno_E1A.
[Graphical view]
PfamPF02703. Adeno_E1A. 1 hit.
[Graphical view]
PIRSFPIRSF003669. Aden_E1A. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP03255.

Entry information

Entry nameE1A_ADE05
AccessionPrimary (citable) accession number: P03255
Secondary accession number(s): P06438, Q64825, Q64826
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references