ID VE6_HPV58 Reviewed; 149 AA. AC P26555; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 07-OCT-2020, entry version 87. DE RecName: Full=Protein E6 {ECO:0000255|HAMAP-Rule:MF_04006}; GN Name=E6 {ECO:0000255|HAMAP-Rule:MF_04006}; OS Human papillomavirus type 58. OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes; OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae; OC Alphapapillomavirus. OX NCBI_TaxID=10598; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1656594; DOI=10.1016/0042-6822(91)90791-9; RA Kirii Y., Iwamoto S., Matsukura T.; RT "Human papillomavirus type 58 DNA sequence."; RL Virology 185:424-427(1991). 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D90400; BAA31845.1; -; Genomic_DNA. DR PIR; E36779; W6WL58. DR SMR; P26555; -. DR IntAct; P26555; 2. DR MINT; P26555; -. DR Proteomes; UP000007668; 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: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; 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..149 FT /note="Protein E6" FT /id="PRO_0000133374" 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" SQ SEQUENCE 149 AA; 17794 MW; 79B3DCC95831B158 CRC64; MFQDAEEKPR TLHDLCQALE TSVHEIELKC VECKKTLQRS EVYDFVFADL RIVYRDGNPF AVCKVCLRLL SKISEYRHYN YSLYGDTLEQ TLKKCLNEIL IRCIICQRPL CPQEKKRHVD LNKRFHNISG RWTGRCAVCW RPRRRQTQV //