UniProtKB - P26554 (VE6_HPV51)
Protein E6
E6
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 annotationMiscellaneous
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 30 – 66 | UniRule annotationAdd BLAST | 37 | |
Zinc fingeri | 103 – 139 | UniRule annotationAdd BLAST | 37 |
GO - Molecular functioni
- DNA binding Source: UniProtKB-UniRule
- metal ion binding Source: UniProtKB-UniRule
- PDZ domain binding Source: UniProtKB-UniRule
GO - Biological processi
- modulation by virus of host apoptotic process Source: UniProtKB-KW
- modulation by virus of host ubiquitin-protein ligase activity Source: UniProtKB-UniRule
- regulation of transcription, DNA-templated Source: UniProtKB-UniRule
- suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-UniRule
- suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity Source: UniProtKB-UniRule
- transcription, DNA-templated Source: UniProtKB-UniRule
Keywordsi
Names & Taxonomyi
Protein namesi | Recommended name: Protein E6UniRule annotation |
Gene namesi | Name:E6UniRule annotation |
Organismi | Human papillomavirus 51 |
Taxonomic identifieri | 10595 [NCBI] |
Taxonomic lineagei | Viruses › Monodnaviria › Shotokuvirae › Cossaviricota › Papovaviricetes › Zurhausenvirales › Papillomaviridae › Firstpapillomavirinae › Alphapapillomavirus › |
Virus hosti | Homo sapiens (Human) [TaxID: 9606] |
Proteomesi |
|
Subcellular locationi
- Host cytoplasm UniRule annotation
- Host nucleus UniRule annotation
Keywords - Cellular componenti
Host cytoplasm, Host nucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000133368 | 1 – 151 | Protein E6Add BLAST | 151 |
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 annotationGO - Molecular functioni
- PDZ domain binding Source: UniProtKB-UniRule
Protein-protein interaction databases
IntActi | P26554, 1 interactor |
MINTi | P26554 |
Structurei
Secondary structure
3D structure databases
BMRBi | P26554 |
SMRi | P26554 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 149 – 151 | PDZ-binding domainUniRule annotation | 3 |
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 30 – 66 | UniRule annotationAdd BLAST | 37 | |
Zinc fingeri | 103 – 139 | UniRule annotationAdd BLAST | 37 |
Keywords - Domaini
Zinc-fingerFamily and domain databases
DisProti | DP02256 |
Gene3Di | 3.30.240.40, 2 hits |
HAMAPi | MF_04006, HPV_E6, 1 hit |
IDEALi | IID90014 |
InterProi | View protein in InterPro IPR001334, E6 IPR038575, E6_sf |
Pfami | View protein in Pfam PF00518, E6, 1 hit |
SUPFAMi | SSF161229, SSF161229, 2 hits |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MFEDKRERPR TLHELCEALN VSMHNIQVVC VYCKKELCRA DVYNVAFTEI
60 70 80 90 100
KIVYRDNNPY AVCKQCLLFY SKIREYRRYS RSVYGTTLEA ITKKSLYDLS
110 120 130 140 150
IRCHRCQRPL GPEEKQKLVD EKKRFHEIAG RWTGQCANCW QRTRQRNETQ
V
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M62877 Genomic DNA No translation available. |
PIRi | E40415, W6WL51 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M62877 Genomic DNA No translation available. |
PIRi | E40415, W6WL51 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2M3L | NMR | - | A | 80-151 | [»] | |
2M3M | NMR | - | B | 142-151 | [»] | |
BMRBi | P26554 | |||||
SMRi | P26554 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | P26554, 1 interactor |
MINTi | P26554 |
Family and domain databases
DisProti | DP02256 |
Gene3Di | 3.30.240.40, 2 hits |
HAMAPi | MF_04006, HPV_E6, 1 hit |
IDEALi | IID90014 |
InterProi | View protein in InterPro IPR001334, E6 IPR038575, E6_sf |
Pfami | View protein in Pfam PF00518, E6, 1 hit |
SUPFAMi | SSF161229, SSF161229, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | VE6_HPV51 | |
Accessioni | P26554Primary (citable) accession number: P26554 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1992 |
Last sequence update: | August 1, 1992 | |
Last modified: | February 23, 2022 | |
This is version 94 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families