ID VE6_HPV68 Reviewed; 158 AA.
AC P54667;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 24-JAN-2024, entry version 89.
DE RecName: Full=Protein E6 {ECO:0000255|HAMAP-Rule:MF_04006};
GN Name=E6 {ECO:0000255|HAMAP-Rule:MF_04006};
OS Human papillomavirus 68.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus; Alphapapillomavirus 7.
OX NCBI_TaxID=45240;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8904450; DOI=10.1128/jcm.34.3.738-744.1996;
RA Longuet M., Beaudenon S., Orth G.;
RT "Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70,
RT related to the potentially oncogenic HPV39.";
RL J. Clin. Microbiol. 34:738-744(1996).
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 -!- INTERACTION:
CC P54667; Q12959: DLG1; Xeno; NbExp=2; IntAct=EBI-11793910, EBI-357481;
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; X67160; CAA47632.1; -; Genomic_DNA.
DR SMR; P54667; -.
DR IntAct; P54667; 1.
DR MINT; P54667; -.
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:0006351; P:DNA-templated transcription; IEA:UniProtKB-UniRule.
DR GO; GO:0039648; P:modulation by symbiont of host protein ubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0039526; P:perturbation by virus of host apoptosis; IEA:UniProtKB-KW.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; 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 Gene3D; 3.30.240.40; E6 early regulatory protein; 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; E6 C-terminal domain-like; 2.
PE 1: Evidence at protein level;
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 Transcription; Transcription regulation; Viral immunoevasion; Zinc;
KW Zinc-finger.
FT CHAIN 1..158
FT /note="Protein E6"
FT /id="PRO_0000133380"
FT ZN_FING 32..68
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04006"
FT ZN_FING 105..141
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04006"
FT MOTIF 156..158
FT /note="PDZ-binding domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04006"
SQ SEQUENCE 158 AA; 18796 MW; 46B37939CFBA6596 CRC64;
MALFHNPEER PYKLPDLCRT LDTTLHDVTI DCVYCRRQLQ RTEVYEFAFS DLCVVYRDGV
PFAACQSCIK FYAKIRELRY YSESVYATTL ETITNTKLYN LLIRCMSCLK PLCPAEKLRH
LTTKRRLHKI AGNFTGQCRH CWTSKREDRR RIRQETQV
//
