ID   VE6_HPV40               Reviewed;         154 AA.
AC   P36812;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   03-AUG-2022, entry version 84.
DE   RecName: Full=Protein E6 {ECO:0000255|HAMAP-Rule:MF_04006};
GN   Name=E6 {ECO:0000255|HAMAP-Rule:MF_04006};
OS   Human papillomavirus 40.
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC   Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC   Alphapapillomavirus.
OX   NCBI_TaxID=10615;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8205838; DOI=10.1007/978-3-642-78487-3_2;
RA   Delius H., Hofmann B.;
RT   "Primer-directed sequencing of human papillomavirus types.";
RL   Curr. Top. Microbiol. Immunol. 186:13-31(1994).
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       {ECO:0000255|HAMAP-Rule:MF_04006}.
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. {ECO:0000255|HAMAP-Rule:MF_04006}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04006}.
CC       Host nucleus {ECO:0000255|HAMAP-Rule:MF_04006}.
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. {ECO:0000255|HAMAP-Rule:MF_04006}.
CC   -!- SIMILARITY: Belongs to the papillomaviridae E6 protein family.
CC       {ECO:0000305}.
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DR   EMBL; X74478; CAA52567.1; -; Genomic_DNA.
DR   PIR; S36555; S36555.
DR   SMR; P36812; -.
DR   Proteomes; UP000009121; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0039649; P:modulation by virus of host ubiquitin-protein ligase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-UniRule.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-UniRule.
DR   Gene3D; 3.30.240.40; -; 2.
DR   HAMAP; MF_04006; HPV_E6; 1.
DR   InterPro; IPR001334; E6.
DR   InterPro; IPR038575; E6_sf.
DR   Pfam; PF00518; E6; 1.
DR   SUPFAM; SSF161229; SSF161229; 2.
PE   3: Inferred from homology;
KW   Activator; DNA-binding; Early protein; Host cytoplasm; Host nucleus;
KW   Host-virus interaction; Inhibition of host innate immune response by virus;
KW   Metal-binding; Modulation of host cell apoptosis by virus;
KW   Reference proteome; Transcription; Transcription regulation;
KW   Viral immunoevasion; Zinc; Zinc-finger.
FT   CHAIN           1..154
FT                   /note="Protein E6"
FT                   /id="PRO_0000133359"
FT   ZN_FING         30..66
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04006"
FT   ZN_FING         103..139
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04006"
SQ   SEQUENCE   154 AA;  17894 MW;  54C90FE52002F5CD CRC64;
     MSARCGSQAR TLYELCDQCN ITLPTLQIDC VFCKTVLKTA EVLAFAFREL YVVWRDDFPH
     AACPRCLDLH GKVNQYRNFR YAAYAPTVEE ETGLTILQVR IRCCKCHKPL SPVEKTNHIV
     KKTQFFKLKD SWTGYCLHCW KKCMEKGQRS ETLC