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P03126 (VE6_HPV16) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein E6
Gene names
Name:E6
OrganismHuman papillomavirus type 16 [Reference proteome]
Taxonomic identifier333760 [NCBI]
Taxonomic lineageVirusesdsDNA viruses, no RNA stagePapillomaviridaeAlphapapillomavirus
Virus hostHomo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length158 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.5 Ref.6

Subunit structure

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subcellular location

Host nucleus matrix.

Miscellaneous

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

Sequence similarities

Belongs to the papillomaviridae E6 protein family.

Ontologies

Keywords
   Biological processHost-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
   Cellular componentHost nucleus
   Developmental stageEarly protein
   DiseaseOncogene
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of Cdc42 GTPase activity

Inferred from direct assay PubMed 21139582. Source: BHF-UCL

modulation by virus of host ubiquitin-protein ligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 21139582. Source: BHF-UCL

suppression by virus of host IRF3 activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host PKR activity

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 nuclear matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from physical interaction PubMed 21139582. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 11275986PubMed 12444549PubMed 12620801PubMed 15492812PubMed 16103886PubMed 16611247PubMed 18977328PubMed 7624774PubMed 8207801PubMed 9467941PubMed 9705868. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 158158Protein E6
PRO_0000133336

Regions

Zinc finger37 – 7337 Potential
Zinc finger110 – 14637 Potential
Motif155 – 1584PDZ-binding By similarity

Experimental info

Sequence conflict171R → G in AAQ10712. Ref.2
Sequence conflict901L → V in AAQ10712. Ref.2

Secondary structure

................................. 158
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03126 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 01FEF5ADCFDB37EB

FASTA15819,187
        10         20         30         40         50         60 
MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC KQQLLRREVY DFAFRDLCIV 

        70         80         90        100        110        120 
YRDGNPYAVC DKCLKFYSKI SEYRHYCYSL YGTTLEQQYN KPLCDLLIRC INCQKPLCPE 

       130        140        150 
EKQRHLDKKQ RFHNIRGRWT GRCMSCCRSS RTRRETQL 

« Hide

References

[1]"Human papillomavirus type 16 DNA sequence."
Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W.G.
Virology 145:181-185(1985) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K02718 Genomic DNA. Translation: AAA46939.1.
AF536179 Genomic DNA. Translation: AAQ10712.1.
D00735 Genomic DNA. Translation: BAA00632.1.
PIRW6WLHS. A03682.
RefSeqNP_041325.1. NC_001526.2.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP03126.
SMRP03126. Positions 88-151.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-44706N.
IntActP03126. 14 interactions.
MINTMINT-96563.

Chemistry

ChEMBLCHEMBL2010633.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID1489078.

Family and domain databases

InterProIPR001334. E6.
[Graphical view]
PfamPF00518. E6. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP03126.

Entry information

Entry nameVE6_HPV16
AccessionPrimary (citable) accession number: P03126
Secondary accession number(s): Q71BI7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 105 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