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Protein

Protein E6

Gene

E6

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

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

GO - Biological processi

  1. activation of 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 transcription Source: CACAO
  7. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  8. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

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

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 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

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

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 – 143Combined sources
Helixi19 – 268Combined sources
Turni30 – 323Combined sources
Turni38 – 403Combined sources
Helixi46 – 549Combined sources
Beta strandi60 – 623Combined sources
Beta strandi65 – 684Combined sources
Helixi71 – 8515Combined sources
Beta strandi86 – 905Combined sources
Helixi92 – 998Combined sources
Helixi103 – 1053Combined sources
Beta strandi106 – 1105Combined sources
Turni111 – 1133Combined sources
Helixi119 – 1279Combined sources
Beta strandi132 – 1354Combined sources
Beta strandi138 – 1414Combined sources
Helixi144 – 1485Combined sources
Beta strandi155 – 1584Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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

        10         20         30         40         50
MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC KQQLLRREVY
60 70 80 90 100
DFAFRDLCIV YRDGNPYAVC DKCLKFYSKI SEYRHYCYSL YGTTLEQQYN
110 120 130 140 150
KPLCDLLIRC INCQKPLCPE EKQRHLDKKQ RFHNIRGRWT GRCMSCCRSS

RTRRETQL
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 (Ref. 2) Curated
Sequence conflicti90 – 901L → V in AAQ10712 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
KEGGivg:1489078.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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...

Protein-protein interaction databases

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

Chemistry

BindingDBiP03126.
ChEMBLiCHEMBL2010633.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1489078.
KEGGivg:1489078.

Miscellaneous databases

EvolutionaryTraceiP03126.
PROiP03126.

Family and domain databases

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

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: April 29, 2015
This is version 112 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

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 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.