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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)DescriptionActionsGraphical viewLength
Zinc fingeri37 – 73Sequence analysisAdd BLAST37
Zinc fingeri110 – 146Sequence analysisAdd BLAST37

GO - Molecular functioni

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

GO - Biological processi

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]
Proteomesi
  • UP000009251 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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 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.
UBE3AQ050863EBI-1177242,EBI-954357From a different organism.

GO - Molecular functioni

  • PDZ domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi4263557. 4 interactors.
DIPiDIP-44706N.
IntActiP03126. 15 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
Motifi155 – 158PDZ-bindingBy similarity4

Sequence similaritiesi

Belongs to the papillomaviridae E6 protein family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri37 – 73Sequence analysisAdd BLAST37
Zinc fingeri110 – 146Sequence analysisAdd BLAST37

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)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.

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_001526.4.

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...

Protein-protein interaction databases

BioGridi4263557. 4 interactors.
DIPiDIP-44706N.
IntActiP03126. 15 interactors.
MINTiMINT-96563.

Chemistry databases

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...

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: November 2, 2016
This is version 124 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

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 one 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.