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Protein

Protein E6

Gene

E6

Organism
Human papillomavirus type 18
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 annotation

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 fingeri32 – 68UniRule annotationAdd BLAST37
Zinc fingeri105 – 141UniRule annotationAdd BLAST37

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • zinc ion binding Source: BHF-UCL

GO - Biological processi

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 18
Taxonomic identifieri333761 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePapillomaviridaeAlphapapillomavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000009109 Componenti: Genome

Subcellular locationi

  • Host cytoplasm UniRule annotation
  • Host nucleus UniRule annotation

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi156 – 158TQV → DQA: Complete loss of binding to MPDZ protein. 1 Publication3
Mutagenesisi158V → A: Complete loss of binding to MPDZ protein. 1 Publication1

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001333381 – 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 annotation6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

DIPiDIP-44730N.
IntActiP06463. 74 interactors.
MINTiMINT-96616.

Structurei

Secondary structure

1158
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi155 – 158Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I04X-ray2.15C/D152-158[»]
2I0IX-ray2.80D/E/F152-158[»]
2I0LX-ray2.31C/D152-158[»]
4JORX-ray1.34C/D149-158[»]
ProteinModelPortaliP06463.
SMRiP06463.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06463.

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 fingeri32 – 68UniRule annotationAdd BLAST37
Zinc fingeri105 – 141UniRule 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.

P06463-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARFEDPTRR PYKLPDLCTE LNTSLQDIEI TCVYCKTVLE LTEVFEFAFK
60 70 80 90 100
DLFVVYRDSI PHAACHKCID FYSRIRELRH YSDSVYGDTL EKLTNTGLYN
110 120 130 140 150
LLIRCLRCQK PLNPAEKLRH LNEKRRFHNI AGHYRGQCHS CCNRARQERL

QRRRETQV
Length:158
Mass (Da):18,872
Last modified:January 1, 1988 - v1
Checksum:i5BCF13CF43D157FA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22N → S in AAA46946 (PubMed:3023067).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04354 Genomic DNA. Translation: CAA27879.1.
X05015 Genomic DNA. Translation: CAA28664.1.
M20325 mRNA. Translation: AAA99514.1.
M26798 Genomic DNA. Translation: AAA46946.1.
X04773 Genomic DNA. Translation: CAA28466.1.
PIRiA26165. W6WL18.
RefSeqiNP_040310.1. NC_001357.1.

Genome annotation databases

GeneIDi1489088.
KEGGivg:1489088.

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.

Entry informationi

Entry nameiVE6_HPV18
AccessioniPrimary (citable) accession number: P06463
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: May 10, 2017
This is version 109 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