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 10-MAY-2017, entry version 75. 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; dsDNA viruses, no RNA stage; Papillomaviridae; 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 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 NFX1, 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: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 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:0000255|HAMAP-Rule:MF_04006}. CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP- CC Rule:MF_04006}. 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 CC unique carboxy terminal PDZ domain containing substrate. CC {ECO:0000255|HAMAP-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 ProteinModelPortal; P26555; -. DR SMR; P26555; -. DR IntAct; P26555; 2. DR MINT; MINT-1537938; -. DR OrthoDB; VOG0900011D; -. 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-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0039548; P:suppression by virus of host IRF3 activity; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR HAMAP; MF_04006; HPV_E6; 1. DR InterPro; IPR001334; E6. DR Pfam; PF00518; E6; 1. PE 3: Inferred from homology; KW Activator; Complete proteome; DNA-binding; Early protein; KW Host cytoplasm; Host nucleus; Host-virus interaction; KW Inhibition of host innate immune response by virus; KW Inhibition of host IRF3 by virus; KW Inhibition of host RLR pathway by virus; Metal-binding; KW Modulation of host cell apoptosis by virus; Oncogene; KW Reference proteome; Transcription; Transcription regulation; KW Viral immunoevasion; Zinc; Zinc-finger. FT CHAIN 1 149 Protein E6. FT /FTId=PRO_0000133374. FT ZN_FING 30 66 {ECO:0000255|HAMAP-Rule:MF_04006}. FT ZN_FING 103 139 {ECO:0000255|HAMAP-Rule:MF_04006}. FT MOTIF 147 149 PDZ-binding domain. {ECO:0000255|HAMAP- FT 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 //