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Annotation rule MF_04006
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General rule information [?]

Accession MF_04006
Dates 14-FEB-2017 (Created)
20-NOV-2019 (Last updated, Version 4)
Name HPV_E6
Scope
Viruses; Papillomaviridae
Templates P06930 (VE6_HPV05); P03126 (VE6_HPV16); P04019 (VE6_HPV11): [Recover all]

Propagated annotation [?]


Identifier, protein and gene names [?]

Identifier
VE6
Protein name
RecName: Full=Protein E6;
Gene name
E6

Comments [?]

case <OC:Alphapapillomavirus> and <FTTag:PDZ>
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 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 NFX-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 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.
Subunit 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.
Subcellular location Host cytoplasm. Host nucleus.
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.
else case <OC:Alphapapillomavirus> and not <FTTag:PDZ>
Function Plays a major role in the induction and maintenance of cellular transformation. E6 associates with host UBE3A/E6-AP ubiquitin-protein ligase and modulates its activity. Sequesters tumor suppressor TP53 in the host cytoplasm and modulates its activity by interacting with host EP300 that results in the reduction of TP53 acetylation and activation. In turn, apoptosis induced by DNA damage is inhibited. E6 protects also host keratinocytes from apoptosis by mediating the degradation of host BAK1. May also inhibit host immune response.
Subunit Forms homodimers. Interacts with ubiquitin-protein ligase UBE3A/E6-AP; this interaction stimulates UBE3A ubiquitin activity. Interacts with host TP53 and EP300; this interaction inhibits TP53 activity.
Subcellular location Host cytoplasm. Host nucleus.
Miscellaneous Belongs to the low risk human alphapapillomavirus family. The cancer-causing human papillomavirus E6 protein has a unique carboxy terminal PDZ domain containing substrate but low risk E6s do not possess this domain.
else
Function Plays a major role in the induction and maintenance of cellular transformation. E6 associates with host UBE3A/E6-AP ubiquitin-protein ligase and modulates its activity. Protects host keratinocytes from apoptosis by mediating the degradation of host BAK1. May also inhibit host immune response.
Subunit Forms homodimers. Interacts with ubiquitin-protein ligase UBE3A/E6-AP; this interaction stimulates UBE3A ubiquitin activity. Interacts with host BAK1.
Subcellular location Host cytoplasm. Host nucleus.
Similarity Belongs to the papillomaviridae E6 protein family.
end case

Keywords [?]

case <OC:Alphapapillomavirus> and <FTTag:PDZ>
end case

Gene Ontology [?]

GO:0003677; Molecular function: DNA binding.
GO:0046872; Molecular function: metal ion binding.
GO:0006355; Biological process: regulation of transcription, DNA-templated.
GO:0006351; Biological process: transcription, DNA-templated.
GO:0039649; Biological process: modulation by virus of host ubiquitin-protein ligase activity.
GO:0039502; Biological process: suppression by virus of host type I interferon-mediated signaling pathway.
case <OC:Alphapapillomavirus> and <FTTag:PDZ>
GO:0030165; Molecular function: PDZ domain binding.
GO:0039548; Biological process: suppression by virus of host IRF3 activity.
end case

Cross-references [?]

Pfam PF00518; E6; 1;

Features [?]

From: VE6_HPV05 (P06930)
Key     From     To       Description   Tag   Condition   FTGroup
ZN_FING     41     77             C-x*-C  
ZN_FING     114     150             C-x*-C  
From: VE6_HPV16 (P03126)
MOTIF (Optional)     Cter-2     Cter       PDZ-binding domain   PDZ   T-x-[VL]  

Additional information [?]

Size range 134-273 amino acids
Related rules None
Fusion None