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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 UBE3A/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/E6AP targets several other substrates to degradation via the proteasome including host DLG1 or NFX1, 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 BAK1, 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.UniRule annotation5 Publications

Miscellaneous

Belongs to the high risk human alphapapillomavirus family. The cancer-causing human papillomavirus E6 protein has a unique carboxy terminal PDZ domain containing substrate.UniRule annotation

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri37 – 73UniRule annotationAdd BLAST37
Zinc fingeri110 – 146UniRule annotationAdd BLAST37

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • PDZ domain binding Source: BHF-UCL

GO - Biological processi

  • activation of GTPase activity Source: BHF-UCL
  • modulation by virus of host apoptotic process Source: UniProtKB-KW
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • suppression by virus of host IRF3 activity Source: UniProtKB-KW
  • suppression by virus of host transcription Source: CACAO
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding
Biological processHost-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host IRF3 by virus, Inhibition of host RLR pathway by virus, Modulation of host cell apoptosis by virus, Transcription, Transcription regulation, Viral immunoevasion
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Protein E6UniRule annotation
Gene namesi
Name:E6UniRule annotation
OrganismiHuman papillomavirus type 16
Taxonomic identifieri333760 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePapillomaviridaeAlphapapillomavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000106302 Componenti: Genome
  • UP000009251 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Keywords - Diseasei

Oncogene

Chemistry databases

ChEMBLiCHEMBL2010633.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001333361 – 158Protein E6Add BLAST158

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Forms homodimers. Interacts with ubiquitin-protein ligase UBE3A/E6-AP and thus forms a complex with human TP53. 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. Interacts with host DLG1; this interaction leads to the proteasomal degradation of DLG1.UniRule annotation12 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • PDZ domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi4263557. 4 interactors.
DIPiDIP-44706N.
ELMiP03126.
IntActiP03126. 16 interactors.
MINTiMINT-96563.

Chemistry databases

BindingDBiP03126.

Structurei

Secondary structure

1158
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni12 – 14Combined sources3
Helixi19 – 25Combined sources7
Turni30 – 32Combined sources3
Turni38 – 40Combined sources3
Helixi46 – 54Combined sources9
Beta strandi60 – 62Combined sources3
Beta strandi65 – 68Combined sources4
Helixi71 – 85Combined sources15
Beta strandi86 – 90Combined sources5
Helixi92 – 99Combined sources8
Helixi103 – 105Combined sources3
Beta strandi108 – 110Combined sources3
Turni111 – 113Combined sources3
Helixi119 – 127Combined sources9
Beta strandi132 – 135Combined sources4
Beta strandi138 – 141Combined sources4
Turni145 – 147Combined sources3
Beta strandi155 – 158Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4XR8X-ray2.25F/H8-158[»]
ProteinModelPortaliP03126.
SMRiP03126.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03126.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi156 – 158PDZ-binding domainUniRule annotation3

Sequence similaritiesi

Belongs to the papillomaviridae E6 protein family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri37 – 73UniRule annotationAdd BLAST37
Zinc fingeri110 – 146UniRule annotationAdd BLAST37

Keywords - Domaini

Zinc-finger

Phylogenomic databases

OrthoDBiVOG0900011D.

Family and domain databases

HAMAPiMF_04006. HPV_E6. 1 hit.
InterProiView protein in InterPro
IPR001334. E6.
PfamiView protein in Pfam
PF00518. E6. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti17R → G in AAQ10712 (Ref. 2) Curated1
Sequence conflicti90L → V in AAQ10712 (Ref. 2) Curated1

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_001526.4.

Genome annotation databases

GeneIDi1489078.
KEGGivg:1489078.

Similar proteinsi

Entry informationi

Entry nameiVE6_HPV16
AccessioniPrimary (citable) accession number: P03126
Secondary accession number(s): Q71BI7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: August 30, 2017
This is version 129 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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