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P03255

- E1A_ADE05

UniProt

P03255 - E1A_ADE05

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
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 1 (21 Jul 1986)
      Previous versions | rss
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    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 – 17421Sequence AnalysisAdd
    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. regulation of transcription, DNA-templated Source: UniProtKB-KW
    5. suppression by virus of host gene expression Source: UniProtKB-KW
    6. suppression by virus of host STAT1 activity Source: UniProtKB-KW
    7. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
    8. transcription, DNA-templated Source: UniProtKB-KW

    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 Curated

    GO - Cellular componenti

    1. host cell nucleus Source: UniProtKB-SubCell

    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 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 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.By similarity5 PublicationsCurated

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Cdkn1bO087692EBI-2603114,EBI-7796656From a different organism.
    CREBBPQ927933EBI-2603114,EBI-81215From a different organism.
    EP300Q094723EBI-6859460,EBI-447295From a different organism.
    KAT2BQ928313EBI-6859460,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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03255.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni41 – 499Interaction with RB1 in competition with E2F1Curated
    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 RB1Sequence Analysis
    Motifi279 – 2835PXDLS motif, CTBP-binding
    Motifi285 – 2895Nuclear localization signalSequence Analysis

    Sequence similaritiesi

    Belongs to the adenoviridae E1A protein family.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri154 – 17421Sequence AnalysisAdd
    BLAST

    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. CuratedVSP_028918Add
    BLAST
    Alternative sequencei56 – 289234Missing in isoform early E1A 6 kDa protein. CuratedVSP_028919Add
    BLAST
    Alternative sequencei140 – 18546Missing in isoform early E1A 26 kDa protein. CuratedVSP_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: October 1, 2014
    This is version 100 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