VE7_HPV18
ID VE7_HPV18 Reviewed; 105 AA.
AC P06788;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 2.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Protein E7 {ECO:0000255|HAMAP-Rule:MF_04004};
GN Name=E7 {ECO:0000255|HAMAP-Rule:MF_04004};
OS Human papillomavirus type 18.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus.
OX NCBI_TaxID=333761;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3039146; DOI=10.1016/0022-2836(87)90343-3;
RA Cole S.T., Danos O.;
RT "Nucleotide sequence and comparative analysis of the human papillomavirus
RT type 18 genome. Phylogeny of papillomaviruses and repeated structure of the
RT E6 and E7 gene products.";
RL J. Mol. Biol. 193:599-608(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2833614; DOI=10.1128/jvi.62.5.1640-1646.1988;
RA Inagaki Y., Tsunokawa Y., Takebe N., Nawa H., Nakanishi S., Terada M.,
RA Sugimura T.;
RT "Nucleotide sequences of cDNAs for human papillomavirus type 18 transcripts
RT in HeLa cells.";
RL J. Virol. 62:1640-1646(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3023067; DOI=10.1002/j.1460-2075.1986.tb04496.x;
RA Schneider-Gaedicke A., Schwarz E.;
RT "Different human cervical carcinoma cell lines show similar transcription
RT patterns of human papillomavirus type 18 early genes.";
RL EMBO J. 5:2285-2292(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3034571; DOI=10.1002/j.1460-2075.1987.tb04731.x;
RA Seedorf K., Oltersdorf T., Kraemer G., Roewekamp W.;
RT "Identification of early proteins of the human papilloma viruses type 16
RT (HPV 16) and type 18 (HPV 18) in cervical carcinoma cells.";
RL EMBO J. 6:139-144(1987).
RN [5]
RP REVIEW.
RX PubMed=11921304; DOI=10.1002/rmv.340;
RA Lee C., Cho Y.;
RT "Interactions of SV40 large T antigen and other viral proteins with
RT retinoblastoma tumour suppressor.";
RL Rev. Med. Virol. 12:81-92(2002).
RN [6]
RP INTERACTION WITH HUMAN TMEM173, FUNCTION, AND MUTAGENESIS OF
RP 25-LEU--GLU-29.
RX PubMed=26405230; DOI=10.1126/science.aab3291;
RA Lau L., Gray E.E., Brunette R.L., Stetson D.B.;
RT "DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway.";
RL Science 350:568-571(2015).
CC -!- FUNCTION: Plays a role in viral genome replication by driving entry of
CC quiescent cells into the cell cycle. Stimulation of progression from G1
CC to S phase allows the virus to efficiently use the cellular DNA
CC replicating machinery to achieve viral genome replication. E7 protein
CC has both transforming and trans-activating activities. Induces the
CC disassembly of the E2F1 transcription factor from RB1, with subsequent
CC transcriptional activation of E2F1-regulated S-phase genes. Interferes
CC with host histone deacetylation mediated by HDAC1 and HDAC2, leading to
CC transcription activation. Also plays a role in the inhibition of both
CC antiviral and antiproliferative functions of host interferon alpha.
CC Interaction with host TMEM173/STING impairs the ability of
CC TMEM173/STING to sense cytosolic DNA and promote the production of type
CC I interferon (IFN-alpha and IFN-beta) (PubMed:26405230).
CC {ECO:0000255|HAMAP-Rule:MF_04004, ECO:0000269|PubMed:26405230}.
CC -!- SUBUNIT: Homodimer. Homooligomer. Interacts with host RB1; this
CC interaction induces dissociation of RB1-E2F1 complex thereby disrupting
CC RB1 activity. Interacts with host EP300; this interaction represses
CC EP300 transcriptional activity. Interacts with protein E2; this
CC interaction inhibits E7 oncogenic activity. Interacts with host
CC TMEM173/STING; this interaction impairs the ability of TMEM173/STING to
CC sense cytosolic DNA and promote the production of type I interferon
CC (IFN-alpha and IFN-beta) (PubMed:26405230). {ECO:0000255|HAMAP-
CC Rule:MF_04004, ECO:0000269|PubMed:26405230}.
CC -!- INTERACTION:
CC P06788; P01106: MYC; Xeno; NbExp=5; IntAct=EBI-1776887, EBI-447544;
CC P06788; P06400: RB1; Xeno; NbExp=4; IntAct=EBI-1776887, EBI-491274;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04004}.
CC Host nucleus {ECO:0000255|HAMAP-Rule:MF_04004}. Note=Predominantly
CC found in the host nucleus. {ECO:0000255|HAMAP-Rule:MF_04004}.
CC -!- DOMAIN: The E7 terminal domain is an intrinsically disordered domain,
CC whose flexibility and conformational transitions confer target
CC adaptability to the oncoprotein. It allows adaptation to a variety of
CC protein targets and exposes the PEST degradation sequence that
CC regulates its turnover in the cell. {ECO:0000255|HAMAP-Rule:MF_04004}.
CC -!- PTM: Highly phosphorylated. {ECO:0000255|HAMAP-Rule:MF_04004}.
CC -!- SIMILARITY: Belongs to the papillomaviridae E7 protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04004}.
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DR EMBL; X05015; CAA28665.1; -; Genomic_DNA.
DR EMBL; M20324; AAA99513.1; -; mRNA.
DR EMBL; M20325; AAA99515.1; -; mRNA.
DR EMBL; M26798; AAA46947.1; -; Genomic_DNA.
DR EMBL; X04773; CAA28467.1; -; Genomic_DNA.
DR EMBL; A06324; CAA00540.1; -; Unassigned_DNA.
DR EMBL; A06328; CAA00543.1; -; Unassigned_RNA.
DR PIR; B26165; W7WL18.
DR PDB; 6IWD; X-ray; 1.80 A; B=54-105.
DR PDBsum; 6IWD; -.
DR SMR; P06788; -.
DR DIP; DIP-45143N; -.
DR IntAct; P06788; 55.
DR MINT; P06788; -.
DR ChEMBL; CHEMBL4802005; -.
DR Proteomes; UP000009109; 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:0003700; F:DNA-binding transcription factor activity; IEA:UniProtKB-UniRule.
DR GO; GO:0019904; F:protein domain specific binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; 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 HAMAP; MF_04004; PPV_E7; 1.
DR InterPro; IPR000148; Papilloma_E7.
DR Pfam; PF00527; E7; 1.
DR PIRSF; PIRSF003407; Papvi_E7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Early protein;
KW G1/S host cell cycle checkpoint dysregulation by virus; Host cytoplasm;
KW Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus; Metal-binding;
KW Modulation of host cell cycle by virus; Oncogene; Reference proteome;
KW Transcription; Transcription regulation; Viral immunoevasion; Zinc;
KW Zinc-finger.
FT CHAIN 1..105
FT /note="Protein E7"
FT /id="PRO_0000133416"
FT ZN_FING 65..101
FT /evidence="ECO:0000250|UniProtKB:P03129"
FT REGION 1..49
FT /note="E7 terminal domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04004"
FT MOTIF 25..29
FT /note="LXCXE motif; interaction with host RB1 and
FT TMEM173/STING"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04004"
FT MOTIF 83..91
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04004"
FT MUTAGEN 25..29
FT /note="LLCHE->VISFD: Abolishes interaction with host
FT TMEM173/STING."
FT /evidence="ECO:0000269|PubMed:26405230"
FT CONFLICT 73
FT /note="K -> E (in Ref. 1 and 4)"
FT /evidence="ECO:0000305"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:6IWD"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:6IWD"
FT STRAND 71..78
FT /evidence="ECO:0007829|PDB:6IWD"
FT HELIX 80..91
FT /evidence="ECO:0007829|PDB:6IWD"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:6IWD"
SQ SEQUENCE 105 AA; 11995 MW; 2CDB119534D0186A CRC64;
MHGPKATLQD IVLHLEPQNE IPVDLLCHEQ LSDSEEENDE IDGVNHQHLP ARRAEPQRHT
MLCMCCKCEA RIKLVVESSA DDLRAFQQLF LNTLSFVCPW CASQQ
