AC   MF_04006;
DC   Protein; auto
TR   HAMAP; MF_04006; -; 1; level=0
XX
Names: HPV_E6
XX
ID   VE6
DE   RecName: Full=Protein E6;
GN   Name=E6;
XX
case <OC:Alphapapillomavirus> and <FTTag:PDZ>
CC   -!- FUNCTION: Plays a major role in the induction and maintenance of
CC       cellular transformation. Acts mainly as an oncoprotein by stimulating
CC       the destruction of many host cell key regulatory proteins. E6
CC       associates with host UBE3A/E6-AP ubiquitin-protein ligase, and
CC       inactivates tumor suppressors TP53 and TP73 by targeting them to the
CC       26S proteasome for degradation. In turn, DNA damage and chromosomal
CC       instabilities increase and lead to cell proliferation and cancer
CC       development. The complex E6/E6AP targets several other substrates to
CC       degradation via the proteasome including host DLG1 or NFX-91, a
CC       repressor of human telomerase reverse transcriptase (hTERT). The
CC       resulting increased expression of hTERT prevents the shortening of
CC       telomere length leading to cell immortalization. Other cellular targets
CC       including BAK1, Fas-associated death domain-containing protein (FADD)
CC       and procaspase 8, are degraded by E6/E6AP causing inhibition of
CC       apoptosis. E6 also inhibits immune response by interacting with host
CC       IRF3 and TYK2. These interactions prevent IRF3 transcriptional
CC       activities and inhibit TYK2-mediated JAK-STAT activation by interferon
CC       alpha resulting in inhibition of the interferon signaling pathway.
CC   -!- SUBUNIT: Forms homodimers. Interacts with ubiquitin-protein ligase
CC       UBE3A/E6-AP and thus forms a complex with human TP53. Interacts with
CC       human NFX1 and MAGI3. Interacts with human IRF3; this interaction
CC       inhibits the establishment of antiviral state. Interacts with human
CC       TYK2; this interaction inhibits JAK-STAT activation by interferon
CC       alpha. Interacts with host DLG1; this interaction leads to the
CC       proteasomal degradation of DLG1.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm. Host nucleus.
CC   -!- MISCELLANEOUS: Belongs to the high risk human alphapapillomavirus
CC       family. The cancer-causing human papillomavirus E6 protein has a unique
CC       carboxy terminal PDZ domain containing substrate.
else case <OC:Alphapapillomavirus> and not <FTTag:PDZ>
CC   -!- FUNCTION: Plays a major role in the induction and maintenance of
CC       cellular transformation. E6 associates with host UBE3A/E6-AP ubiquitin-
CC       protein ligase and modulates its activity. Sequesters tumor suppressor
CC       TP53 in the host cytoplasm and modulates its activity by interacting
CC       with host EP300 that results in the reduction of TP53 acetylation and
CC       activation. In turn, apoptosis induced by DNA damage is inhibited. E6
CC       protects also host keratinocytes from apoptosis by mediating the
CC       degradation of host BAK1. May also inhibit host immune response.
CC   -!- SUBUNIT: Forms homodimers. Interacts with ubiquitin-protein ligase
CC       UBE3A/E6-AP; this interaction stimulates UBE3A ubiquitin activity.
CC       Interacts with host TP53 and EP300; this interaction inhibits TP53
CC       activity.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm. Host nucleus.
CC   -!- MISCELLANEOUS: Belongs to the low risk human alphapapillomavirus
CC       family. The cancer-causing human papillomavirus E6 protein has a unique
CC       carboxy terminal PDZ domain containing substrate but low risk E6s do
CC       not possess this domain.
else
CC   -!- FUNCTION: Plays a major role in the induction and maintenance of
CC       cellular transformation. E6 associates with host UBE3A/E6-AP ubiquitin-
CC       protein ligase and modulates its activity. Protects host keratinocytes
CC       from apoptosis by mediating the degradation of host BAK1. May also
CC       inhibit host immune response.
CC   -!- SUBUNIT: Forms homodimers. Interacts with ubiquitin-protein ligase
CC       UBE3A/E6-AP; this interaction stimulates UBE3A ubiquitin activity.
CC       Interacts with host BAK1.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm. Host nucleus.
CC   -!- SIMILARITY: Belongs to the papillomaviridae E6 protein family.
end case
XX
DR   Pfam; PF00518; E6; 1; trigger=no
XX
KW   Activator
KW   DNA-binding
KW   Early protein
KW   Host cytoplasm
KW   Host nucleus
KW   Host-virus interaction
KW   Inhibition of host innate immune response by virus
case <OC:Alphapapillomavirus> and <FTTag:PDZ>
KW   Inhibition of host IRF3 by virus
KW   Inhibition of host RLR pathway by virus
end case
KW   Metal-binding
KW   Modulation of host cell apoptosis by virus
KW   Transcription
KW   Transcription regulation
KW   Viral immunoevasion
KW   Zinc
KW   Zinc-finger
XX
GO   GO:0003677; F:DNA binding
GO   GO:0046872; F:metal ion binding
GO   GO:0006355; P:regulation of DNA-templated transcription
GO   GO:0006351; P:DNA-templated transcription
GO   GO:0039648; P:modulation by symbiont of host protein ubiquitination
GO   GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway
case <OC:Alphapapillomavirus> and <FTTag:PDZ>
GO   GO:0030165; F:PDZ domain binding
GO   GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity
end case
XX
FT   From: VE6_HPV05 (P06930)
FT   ZN_FING         41..77
FT   Condition: C-x*-C
FT   ZN_FING         114..150
FT   Condition: C-x*-C
FT   From: VE6_HPV16 (P03126)
FT   MOTIF           Cter-2..Cter
FT                   /note="PDZ-binding domain"
FT   Tag: PDZ; Optional; Condition: T-x-[VL]
XX
Size: 134-273;
Related: None;
Template: P06930; P03126; P04019;
Scope:
 Viruses; Papillomaviridae
Fusion:
 Nter: None
 Cter: None
Duplicate: None
Plasmid: None
Comments: None
XX
# Revision 1.8 2023/02/09
//