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P03126

- VE6_HPV16

UniProt

P03126 - VE6_HPV16

Protein

Protein E6

Gene

E6

Organism
Human papillomavirus type 16
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6P targets several other substrates to degradation via the proteasome including host NFX1-91, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including Bak, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri37 – 7337Sequence AnalysisAdd
    BLAST
    Zinc fingeri110 – 14637Sequence AnalysisAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. PDZ domain binding Source: BHF-UCL
    4. protein binding Source: IntAct

    GO - Biological processi

    1. activation of Cdc42 GTPase activity Source: BHF-UCL
    2. modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-KW
    3. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    4. suppression by virus of host IRF3 activity Source: UniProtKB-KW
    5. suppression by virus of host PKR activity 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

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host IRF3 by virus, Inhibition of host PKR by virus, Inhibition of host RLR pathway by virus, Modulation of host E3 ubiquitin ligases by virus, Modulation of host ubiquitin pathway by virus, Transcription, Transcription regulation, Viral immunoevasion

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_1432. TNF signaling.
    REACT_402. TRAIL signaling.
    REACT_900. FasL/ CD95L signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein E6
    Gene namesi
    Name:E6
    OrganismiHuman papillomavirus type 16
    Taxonomic identifieri333760 [NCBI]
    Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePapillomaviridaeAlphapapillomavirus
    Virus hostiHomo sapiens (Human) [TaxID: 9606]
    ProteomesiUP000009251: Genome

    Subcellular locationi

    GO - Cellular componenti

    1. host cell nuclear matrix Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Host nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 158158Protein E6PRO_0000133336Add
    BLAST

    Expressioni

    Keywords - Developmental stagei

    Early protein

    Interactioni

    Subunit structurei

    Forms a complex E6-AP ubiquitin-protein ligase which interacts with human TP53. Binds to human FBLN1 and MPDZ By similarity. Interacts with human NFX1 and MAGI3. Interacts with human IRF3; this interaction inhibits the establishment of antiviral state. Interacts with human TYK2; this interaction inhibits JAK-STAT activation by interferon alpha.By similarity7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DLG1Q129592EBI-1177242,EBI-357481From a different organism.
    MCM7P339932EBI-1177242,EBI-355924From a different organism.
    PXNP490242EBI-1177242,EBI-2896280From a different organism.
    RCN2Q142572EBI-1177242,EBI-356710From a different organism.
    SCRIBQ141605EBI-1177242,EBI-357345From a different organism.
    TAX1BP3O149072EBI-1177242,EBI-723259From a different organism.
    TP53P046373EBI-1177242,EBI-366083From a different organism.
    TP73O15350-12EBI-1177242,EBI-389619From a different organism.
    UBE3AQ050862EBI-1177242,EBI-954357From a different organism.

    Protein-protein interaction databases

    DIPiDIP-44706N.
    IntActiP03126. 14 interactions.
    MINTiMINT-96563.

    Structurei

    Secondary structure

    1
    158
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni12 – 143
    Helixi19 – 268
    Turni30 – 323
    Turni38 – 403
    Helixi46 – 549
    Beta strandi60 – 623
    Beta strandi65 – 684
    Helixi71 – 8515
    Beta strandi86 – 905
    Helixi92 – 998
    Helixi103 – 1053
    Beta strandi106 – 1105
    Turni111 – 1133
    Helixi119 – 1279
    Beta strandi132 – 1354
    Beta strandi138 – 1414
    Helixi144 – 1485
    Beta strandi155 – 1584

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1VZNmodel-A1-158[»]
    2FK4NMR-A87-158[»]
    2KPLNMR-B148-157[»]
    2LJXNMR-A7-89[»]
    2LJYNMR-A/B7-89[»]
    2LJZNMR-A87-158[»]
    4GIZX-ray2.55C/D9-150[»]
    4JOPX-ray1.80C/D152-158[»]
    ProteinModelPortaliP03126.
    SMRiP03126. Positions 88-151.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03126.

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi155 – 1584PDZ-bindingBy similarity

    Sequence similaritiesi

    Belongs to the papillomaviridae E6 protein family.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri37 – 7337Sequence AnalysisAdd
    BLAST
    Zinc fingeri110 – 14637Sequence AnalysisAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Family and domain databases

    InterProiIPR001334. E6.
    [Graphical view]
    PfamiPF00518. E6. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P03126-1 [UniParc]FASTAAdd to Basket

    « Hide

    MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC KQQLLRREVY    50
    DFAFRDLCIV YRDGNPYAVC DKCLKFYSKI SEYRHYCYSL YGTTLEQQYN 100
    KPLCDLLIRC INCQKPLCPE EKQRHLDKKQ RFHNIRGRWT GRCMSCCRSS 150
    RTRRETQL 158
    Length:158
    Mass (Da):19,187
    Last modified:July 21, 1986 - v1
    Checksum:i01FEF5ADCFDB37EB
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti17 – 171R → G in AAQ10712. 1 PublicationCurated
    Sequence conflicti90 – 901L → V in AAQ10712. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K02718 Genomic DNA. Translation: AAA46939.1.
    AF536179 Genomic DNA. Translation: AAQ10712.1.
    D00735 Genomic DNA. Translation: BAA00632.1.
    PIRiA03682. W6WLHS.
    RefSeqiNP_041325.1. NC_001526.2.

    Genome annotation databases

    GeneIDi1489078.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    K02718 Genomic DNA. Translation: AAA46939.1 .
    AF536179 Genomic DNA. Translation: AAQ10712.1 .
    D00735 Genomic DNA. Translation: BAA00632.1 .
    PIRi A03682. W6WLHS.
    RefSeqi NP_041325.1. NC_001526.2.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1VZN model - A 1-158 [» ]
    2FK4 NMR - A 87-158 [» ]
    2KPL NMR - B 148-157 [» ]
    2LJX NMR - A 7-89 [» ]
    2LJY NMR - A/B 7-89 [» ]
    2LJZ NMR - A 87-158 [» ]
    4GIZ X-ray 2.55 C/D 9-150 [» ]
    4JOP X-ray 1.80 C/D 152-158 [» ]
    ProteinModelPortali P03126.
    SMRi P03126. Positions 88-151.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-44706N.
    IntActi P03126. 14 interactions.
    MINTi MINT-96563.

    Chemistry

    ChEMBLi CHEMBL2010633.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 1489078.

    Enzyme and pathway databases

    Reactomei REACT_1432. TNF signaling.
    REACT_402. TRAIL signaling.
    REACT_900. FasL/ CD95L signaling.

    Miscellaneous databases

    EvolutionaryTracei P03126.

    Family and domain databases

    InterProi IPR001334. E6.
    [Graphical view ]
    Pfami PF00518. E6. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Cloning and sequencing of non-European human papillomavirus (HPV) variant complete genomes from cervicovaginal cells by an overlapping PCR method."
      Terai M., Fu L., Ma Z., Burk R.D.
      Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: Isolate European German 131.
    3. "Expression of the human papillomavirus type 16 genome in SK-v cells, a line derived from a vulvar intraepithelial neoplasia."
      Schneider-Maunoury S., Pehau-Arnaudet G., Breitburd F., Orth G.
      J. Gen. Virol. 71:809-817(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-50.
    4. "Telomerase activation by the E6 gene product of human papillomavirus type 16."
      Klingelhutz A.J., Foster S.A., McDougall J.K.
      Nature 380:79-82(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity."
      Ronco L.V., Karpova A.Y., Vidal M., Howley P.M.
      Genes Dev. 12:2061-2072(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HOST IRF3.
    6. "The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha."
      Li S., Labrecque S., Gauzzi M.C., Cuddihy A.R., Wong A.H., Pellegrini S., Matlashewski G.J., Koromilas A.E.
      Oncogene 18:5727-5737(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HOST TYK2.
    7. "Interaction of oncogenic papillomavirus E6 proteins with fibulin-1."
      Du M., Fan X., Hong E., Chen J.J.
      Biochem. Biophys. Res. Commun. 296:962-969(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN FBLN1, INHIBITION OF E6-MEDIATED TRANSFORMATION.
    8. "Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex."
      Gewin L., Myers H., Kiyono T., Galloway D.A.
      Genes Dev. 18:2269-2282(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN NFX1.
    9. "Oncogenic human papillomavirus E6 proteins target the MAGI-2 and MAGI-3 proteins for degradation."
      Thomas M., Laura R., Hepner K., Guccione E., Sawyers C., Lasky L., Banks L.
      Oncogene 21:5088-5096(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN MAGI3.
    10. "Role of the PDZ domain-binding motif of the oncoprotein E6 in the pathogenesis of human papillomavirus type 31."
      Lee C., Laimins L.A.
      J. Virol. 78:12366-12377(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN MAGI3.
    11. "HPV E6 specifically targets different cellular pools of its PDZ domain-containing tumour suppressor substrates for proteasome-mediated degradation."
      Massimi P., Gammoh N., Thomas M., Banks L.
      Oncogene 23:8033-8039(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN MAGI3.
    12. "Cellular and molecular biological aspects of cervical intraepithelial neoplasia."
      Kisseljov F., Sakharova O., Kondratjeva T.
      Int. Rev. Cytol. 271:35-95(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiVE6_HPV16
    AccessioniPrimary (citable) accession number: P03126
    Secondary accession number(s): Q71BI7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: October 1, 2014
    This is version 107 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    HPV16, in comparison to HPV types 6 and 11, is more often associated with malignant genital cancers in humans.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference 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