ID   VE6_HPV69               Reviewed;         151 AA.
AC   Q9JH51;
DT   27-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   23-FEB-2022, entry version 80.
DE   RecName: Full=Protein E6 {ECO:0000255|HAMAP-Rule:MF_04006};
GN   Name=E6 {ECO:0000255|HAMAP-Rule:MF_04006};
OS   Human papillomavirus 69.
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC   Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC   Alphapapillomavirus.
OX   NCBI_TaxID=37121;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10618284; DOI=10.1128/cdli.7.1.91-95.2000;
RA   Kino N., Sata T., Sato Y., Sugase M., Matsukura T.;
RT   "Molecular cloning and nucleotide sequence analysis of a novel human
RT   papillomavirus (type 82) associated with vaginal intraepithelial
RT   neoplasia.";
RL   Clin. Diagn. Lab. Immunol. 7:91-95(2000).
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 NFX1, a repressor
CC       of human telomerase reverse transcriptase (hTERT). The resulting
CC       increased expression of hTERT prevents the shortening of telomere
CC       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       {ECO:0000255|HAMAP-Rule:MF_04006}.
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. {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 high risk human alphapapillomavirus
CC       family. The cancer-causing human papillomavirus E6 protein has a unique
CC       carboxy terminal PDZ domain containing substrate. {ECO:0000255|HAMAP-
CC       Rule:MF_04006}.
CC   -!- SIMILARITY: Belongs to the papillomaviridae E6 protein family.
CC       {ECO:0000305}.
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DR   EMBL; AB027020; BAA90727.1; -; Genomic_DNA.
DR   SMR; Q9JH51; -.
DR   Proteomes; UP000007674; 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:0030165; F:PDZ domain 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:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; 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   Inhibition of host IRF3 by virus; Inhibition of host RLR pathway by virus;
KW   Metal-binding; Modulation of host cell apoptosis by virus; Oncogene;
KW   Reference proteome; Transcription; Transcription regulation;
KW   Viral immunoevasion; Zinc; Zinc-finger.
FT   CHAIN           1..151
FT                   /note="Protein E6"
FT                   /id="PRO_0000133381"
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"
FT   MOTIF           149..151
FT                   /note="PDZ-binding domain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04006"
SQ   SEQUENCE   151 AA;  17945 MW;  8F681A0E3A71F6E9 CRC64;
     MFQDPRERPR TIHELCEALN TPLQSLQVQC VYCKKTLEWA DVYNFAICDL RIVYRNDSAY
     GACKKCIIFY SKIIEYRRYT SSVYGATLEA RPKRSLCNLL IRCHRCQIPL GPEEKQRIVD
     EKRRFHEIAG YWKGLCTNCW RPRREATETQ V