VE6_HPV31
ID VE6_HPV31 Reviewed; 149 AA.
AC P17386;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 23-FEB-2022, entry version 107.
DE RecName: Full=Protein E6 {ECO:0000255|HAMAP-Rule:MF_04006};
GN Name=E6 {ECO:0000255|HAMAP-Rule:MF_04006};
OS Human papillomavirus 31.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus.
OX NCBI_TaxID=10585;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2545036; DOI=10.1016/0042-6822(89)90545-x;
RA Goldsborough M.D., Disilvestre D., Temple G.F., Lorincz A.T.;
RT "Nucleotide sequence of human papillomavirus type 31: a cervical neoplasia-
RT associated virus.";
RL Virology 171:306-311(1989).
RN [2]
RP INTERACTION WITH HUMAN FBLN1, AND INHIBITION OF E6-MEDIATED TRANSFORMATION.
RX PubMed=12200142; DOI=10.1016/s0006-291x(02)02041-7;
RA Du M., Fan X., Hong E., Chen J.J.;
RT "Interaction of oncogenic papillomavirus E6 proteins with fibulin-1.";
RL Biochem. Biophys. Res. Commun. 296:962-969(2002).
RN [3]
RP PDZ DOMAIN-BINDING MOTIF.
RX PubMed=15507623; DOI=10.1128/jvi.78.22.12366-12377.2004;
RA Lee C., Laimins L.A.;
RT "Role of the PDZ domain-binding motif of the oncoprotein E6 in the
RT pathogenesis of human papillomavirus type 31.";
RL J. Virol. 78:12366-12377(2004).
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 P17386; Q12959: DLG1; Xeno; NbExp=2; IntAct=EBI-8516807, 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; J04353; AAA46950.1; -; Genomic_DNA.
DR PIR; A32444; W6WL31.
DR PDB; 6SLM; X-ray; 2.80 A; A=1-149.
DR PDBsum; 6SLM; -.
DR SMR; P17386; -.
DR IntAct; P17386; 5.
DR MINT; P17386; -.
DR Proteomes; UP000009116; 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 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Early protein; Host cytoplasm;
KW Host nucleus; Host-virus interaction;
KW 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..149
FT /note="Protein E6"
FT /id="PRO_0000133351"
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 147..149
FT /note="PDZ-binding domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04006"
FT STRAND 1..3
FT /evidence="ECO:0007829|PDB:6SLM"
FT STRAND 5..7
FT /evidence="ECO:0007829|PDB:6SLM"
FT HELIX 12..19
FT /evidence="ECO:0007829|PDB:6SLM"
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:6SLM"
FT TURN 31..33
FT /evidence="ECO:0007829|PDB:6SLM"
FT HELIX 39..47
FT /evidence="ECO:0007829|PDB:6SLM"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:6SLM"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:6SLM"
FT HELIX 64..77
FT /evidence="ECO:0007829|PDB:6SLM"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:6SLM"
FT HELIX 85..92
FT /evidence="ECO:0007829|PDB:6SLM"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:6SLM"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:6SLM"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:6SLM"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:6SLM"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:6SLM"
FT TURN 138..141
FT /evidence="ECO:0007829|PDB:6SLM"
SQ SEQUENCE 149 AA; 17714 MW; 61D2A86C362767D9 CRC64;
MFKNPAERPR KLHELSSALE IPYDELRLNC VYCKGQLTET EVLDFAFTDL TIVYRDDTPH
GVCTKCLRFY SKVSEFRWYR YSVYGTTLEK LTNKGICDLL IRCITCQRPL CPEEKQRHLD
KKKRFHNIGG RWTGRCIACW RRPRTETQV
