ID   A0A0U2QTG8_HPV16        Unreviewed;       158 AA.
AC   A0A0U2QTG8;
DT   16-MAR-2016, integrated into UniProtKB/TrEMBL.
DT   16-MAR-2016, sequence version 1.
DT   05-JUN-2019, entry version 15.
DE   RecName: Full=Protein E6 {ECO:0000256|HAMAP-Rule:MF_04006, ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013181};
GN   Name=E6 {ECO:0000256|HAMAP-Rule:MF_04006,
GN   ECO:0000313|EMBL:ALU65790.1};
OS   Human papillomavirus type 16.
OC   Viruses; Papillomaviridae; Firstpapillomavirinae; Alphapapillomavirus.
OX   NCBI_TaxID=333760 {ECO:0000313|EMBL:ALU65790.1};
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1] {ECO:0000313|EMBL:ALU65790.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=HPV16Hap78 {ECO:0000313|EMBL:ALU65790.1};
RX   PubMed=26694554;
RA   Vidal J.P., Felix S.P., Chaves C.B., Patury P., Franco V.F.,
RA   de Morais E.A., de Carvalho N.A., Carvalho A.C., Neto O.F.,
RA   Vieira L.M., Correa F.M., Martins L.F., Negrao A., de Almeida L.M.,
RA   Moreira M.A.;
RT   "Genetic diversity of HPV16 and HPV18 in Brazilian patients with
RT   invasive cervical cancer.";
RL   J. Med. Virol. 0:0-0(2015).
CC   -!- FUNCTION: Plays a major role in the induction and maintenance of
CC       cellular transformation. Acts mainly as an oncoprotein by
CC       stimulating the destruction of many host cell key regulatory
CC       proteins. E6 associates with host UBE3A/E6-AP ubiquitin-protein
CC       ligase, and inactivates tumor suppressors TP53 and TP73 by
CC       targeting them to the 26S proteasome for degradation. In turn, DNA
CC       damage and chromosomal instabilities increase and lead to cell
CC       proliferation and cancer development. The complex E6/E6AP targets
CC       several other substrates to degradation via the proteasome
CC       including host DLG1 or NFX-91, a repressor of human telomerase
CC       reverse transcriptase (hTERT). The resulting increased expression
CC       of hTERT prevents the shortening of telomere length leading to
CC       cell immortalization. Other cellular targets including BAK1, Fas-
CC       associated death domain-containing protein (FADD) and procaspase
CC       8, are degraded by E6/E6AP causing inhibition of apoptosis. E6
CC       also inhibits immune response by interacting with host IRF3 and
CC       TYK2. These interactions prevent IRF3 transcriptional activities
CC       and inhibit TYK2-mediated JAK-STAT activation by interferon alpha
CC       resulting in inhibition of the interferon signaling pathway.
CC       {ECO:0000256|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
CC       with human NFX1 and MAGI3. Interacts with human IRF3; this
CC       interaction inhibits the establishment of antiviral state.
CC       Interacts with human TYK2; this interaction inhibits JAK-STAT
CC       activation by interferon alpha. Interacts with host DLG1; this
CC       interaction leads to the proteasomal degradation of DLG1.
CC       {ECO:0000256|HAMAP-Rule:MF_04006}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000256|HAMAP-
CC       Rule:MF_04006, ECO:0000256|RuleBase:RU363123}. Host nucleus
CC       {ECO:0000256|HAMAP-Rule:MF_04006, ECO:0000256|RuleBase:RU363123,
CC       ECO:0000256|SAAS:SAAS01013177}.
CC   -!- MISCELLANEOUS: Belongs to the high risk human alphapapillomavirus
CC       family. The cancer-causing human papillomavirus E6 protein has a
CC       unique carboxy terminal PDZ domain containing substrate.
CC       {ECO:0000256|HAMAP-Rule:MF_04006}.
CC   -!- SIMILARITY: Belongs to the papillomaviridae E6 protein family.
CC       {ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013174}.
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DR   EMBL; KP965095; ALU65790.1; -; Genomic_DNA.
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:0039548; P:suppression by virus of host IRF3 activity; 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 {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013178};
KW   DNA-binding {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013184};
KW   Early protein {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123};
KW   Host cytoplasm {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|SAAS:SAAS01013183};
KW   Host nucleus {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013175};
KW   Host-virus interaction {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|SAAS:SAAS01013182};
KW   Inhibition of host innate immune response by virus {ECO:0000256|HAMAP-
KW   Rule:MF_04006, ECO:0000256|SAAS:SAAS01013176};
KW   Inhibition of host IRF3 by virus {ECO:0000256|HAMAP-Rule:MF_04006};
KW   Inhibition of host RLR pathway by virus {ECO:0000256|HAMAP-
KW   Rule:MF_04006};
KW   Metal-binding {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013173};
KW   Modulation of host cell apoptosis by virus {ECO:0000256|HAMAP-
KW   Rule:MF_04006, ECO:0000256|SAAS:SAAS01013180};
KW   Transcription {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013169};
KW   Transcription regulation {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013179};
KW   Viral immunoevasion {ECO:0000256|HAMAP-Rule:MF_04006};
KW   Zinc {ECO:0000256|HAMAP-Rule:MF_04006, ECO:0000256|RuleBase:RU363123,
KW   ECO:0000256|SAAS:SAAS01013172};
KW   Zinc-finger {ECO:0000256|HAMAP-Rule:MF_04006,
KW   ECO:0000256|RuleBase:RU363123, ECO:0000256|SAAS:SAAS01013170}.
FT   ZN_FING      37     73       {ECO:0000256|HAMAP-Rule:MF_04006}.
FT   ZN_FING     110    146       {ECO:0000256|HAMAP-Rule:MF_04006}.
FT   MOTIF       156    158       PDZ-binding domain. {ECO:0000256|HAMAP-
FT                                Rule:MF_04006}.
SQ   SEQUENCE   158 AA;  19130 MW;  9F0CF5ADCD9977FE CRC64;
     MHQKRTAMFQ DPQERPRKLP QLCTELQTTI HDIILECVYC KQQLLRREVY DFAFRDLCIV
     YRDGNPYAVC DKCLKFYSKI SEYRHYCYSV YGTTLEQQYN KPLCDLLIRC INCQKPLCPE
     EKQRHLDKKQ RFHNIRGLWT GRCMSCCRSS RTRRETQL
//