SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P03255

- E1A_ADE05

UniProt

P03255 - E1A_ADE05

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Early E1A 32 kDa protein

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

Functioni

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 early E1A 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.4 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri154 – 17421 Reviewed predictionAdd
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. protein binding Source: IntAct

GO - Biological processi

  1. modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
  2. modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-KW
  3. positive regulation of cell proliferation Source: BHF-UCL
  4. suppression by virus of host STAT1 activity Source: UniProtKB-KW
  5. suppression by virus of host transcription initiation from RNA polymerase II promoter Source: UniProtKB-KW
  6. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  7. transcription, DNA-templated Source: UniProtKB-KW
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 32 kDa protein
OrganismiHuman adenovirus C serotype 5 (HAdV-5) (Human adenovirus 5)
Taxonomic identifieri28285 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageAdenoviridaeMastadenovirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000004992: Genome

Subcellular locationi

Host nucleus Reviewed prediction

GO - Cellular componenti

  1. host cell nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi115 – 1151L → A: Complete loss of interaction with host ZMYND11. 1 Publication
Mutagenesisi122 – 1221L → I: Abolishes binding to UBE2I. 1 Publication
Mutagenesisi154 – 1541C → S: Loss of transactivation. 1 Publication
Mutagenesisi157 – 1571C → S: Loss of transactivation. 1 Publication
Mutagenesisi171 – 1711C → S: Loss of transactivation. 1 Publication
Mutagenesisi174 – 1741C → S: Loss of transactivation. 1 Publication

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 289289Early E1A 32 kDa proteinPRO_0000221694Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei89 – 891Phosphoserine; by host1 Publication
Modified residuei219 – 2191Phosphoserine; by host1 Publication
Modified residuei231 – 2311Phosphoserine; by host1 Publication

Keywords - PTMi

Phosphoprotein

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Interacts with host UBE2I; this interaction interferes with polySUMOylation Inferred. 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 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. 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.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cdkn1bO087692EBI-2603114,EBI-7796656From a different organism.
CREBBPQ927933EBI-2603114,EBI-81215From a different organism.
EP300Q094723EBI-2603114,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.

Protein-protein interaction databases

DIPiDIP-40736N.
IntActiP03255. 33 interactions.
MINTiMINT-87547.

Structurei

Secondary structure

1
289
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi43 – 464
Helixi59 – 635
Beta strandi68 – 703
Helixi72 – 743
Helixi80 – 823

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KJENMR-B53-91[»]
2R7GX-ray1.67B/D/E40-49[»]
ProteinModelPortaliP03255.

Miscellaneous databases

EvolutionaryTraceiP03255.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni41 – 499Interaction with RB1 in competition with E2F1 Inferred
Regioni76 – 14065Interaction with UBE2IAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi113 – 1175PXLXP motif, interaction with host ZMYND11
Motifi122 – 1265LXCXE motif, interaction with host RB1 Reviewed prediction
Motifi279 – 2835PXDLS motif, CTBP-binding
Motifi285 – 2895Nuclear localization signal Reviewed prediction

Sequence similaritiesi

Keywords - Domaini

Zinc-finger

Family and domain databases

InterProiIPR014410. Aden_E1A.
IPR003853. Adeno_E1A.
[Graphical view]
PfamiPF02703. Adeno_E1A. 1 hit.
[Graphical view]
PIRSFiPIRSF003669. Aden_E1A. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

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

Isoform early E1A 32 kDa protein (identifier: P03255-1) [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

MRHIICHGGV ITEEMAASLL DQLIEEVLAD NLPPPSHFEP PTLHELYDLD    50
VTAPEDPNEE AVSQIFPDSV MLAVQEGIDL LTFPPAPGSP EPPHLSRQPE 100
QPEQRALGPV SMPNLVPEVI DLTCHEAGFP PSDDEDEEGE EFVLDYVEHP 150
GHGCRSCHYH RRNTGDPDIM CSLCYMRTCG MFVYSPVSEP EPEPEPEPEP 200
ARPTRRPKMA PAILRRPTSP VSRECNSSTD SCDSGPSNTP PEIHPVVPLC 250
PIKPVAVRVG GRRQAVECIE DLLNEPGQPL DLSCKRPRP 289
Length:289
Mass (Da):31,851
Last modified:July 21, 1986 - v1
Checksum:i8C5997A3908C40D7
GO
Isoform early E1A 26 kDa protein (identifier: P03255-2) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:243
Mass (Da):26,452
Checksum:iCA355781A92A4D42
GO
Isoform early E1A 6 kDa protein (identifier: P03255-3) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:55
Mass (Da):6,156
Checksum:i001555BAD0415F3A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei29 – 5527ADNLP…VTAPE → CLNLSLSPSQNRSLQDLPAV LKWRLLS in isoform early E1A 6 kDa protein. VSP_028918Add
BLAST
Alternative sequencei56 – 289234Missing in isoform early E1A 6 kDa protein. VSP_028919Add
BLAST
Alternative sequencei140 – 18546Missing in isoform early E1A 26 kDa protein. VSP_000198Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
PIRiA03825. ERAD65.
C03824. Q2AD5.
RefSeqiAP_000197.1. AC_000008.1. [P03255-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2KJE NMR - B 53-91 [» ]
2R7G X-ray 1.67 B/D/E 40-49 [» ]
ProteinModelPortali P03255.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-40736N.
IntActi P03255. 33 interactions.
MINTi MINT-87547.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P03255.

Family and domain databases

InterProi IPR014410. Aden_E1A.
IPR003853. Adeno_E1A.
[Graphical view ]
Pfami PF02703. Adeno_E1A. 1 hit.
[Graphical view ]
PIRSFi PIRSF003669. Aden_E1A. 1 hit.
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiE1A_ADE05
AccessioniPrimary (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: September 3, 2014
This is version 99 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

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi