VE7_HPV16
ID VE7_HPV16 Reviewed; 98 AA.
AC P03129;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Protein E7 {ECO:0000255|HAMAP-Rule:MF_04004};
GN Name=E7 {ECO:0000255|HAMAP-Rule:MF_04004};
OS Human papillomavirus type 16.
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Papovaviricetes;
OC Zurhausenvirales; Papillomaviridae; Firstpapillomavirinae;
OC Alphapapillomavirus.
OX NCBI_TaxID=333760;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2990099; DOI=10.1016/0042-6822(85)90214-4;
RA Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W.G.;
RT "Human papillomavirus type 16 DNA sequence.";
RL Virology 145:181-185(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2157796; DOI=10.1099/0022-1317-71-4-809;
RA Schneider-Maunoury S., Pehau-Arnaudet G., Breitburd F., Orth G.;
RT "Expression of the human papillomavirus type 16 genome in SK-v cells, a
RT line derived from a vulvar intraepithelial neoplasia.";
RL J. Gen. Virol. 71:809-817(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9292007; DOI=10.1099/0022-1317-78-9-2199;
RA Tornesello M.L., Buonaguro F.M., Meglio A., Buonaguro L., Beth-Giraldo E.,
RA Giraldo G.;
RT "Sequence variations and viral genomic state of human papillomavirus type
RT 16 in penile carcinomas from Ugandan patients.";
RL J. Gen. Virol. 78:2199-2208(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Song Y.S., Kee S.H., Kim J.W., Park N.H., Kang S.B., Lee H.P.;
RT "Major sequence variations in E7 gene of human papillomavirus type 16 from
RT cervical cancerous and non-cancerous lesions of Korean women.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Isolate African 1, and Isolate European German 131;
RA Terai M., Fu L., Ma Z., Burk R.D.;
RT "Cloning and sequencing of non-European human papillomavirus (HPV) variant
RT complete genomes from cervicovaginal cells by an overlapping PCR method.";
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=3033296; DOI=10.1128/jvi.61.5.1686-1689.1987;
RA Smotkin D., Wettstein F.O.;
RT "The major human papillomavirus protein in cervical cancers is a
RT cytoplasmic phosphoprotein.";
RL J. Virol. 61:1686-1689(1987).
RN [7]
RP FUNCTION.
RX PubMed=2836062; DOI=10.1016/0092-8674(88)90570-3;
RA Phelps W.C., Yee C.L., Munger K., Howley P.M.;
RT "The human papillomavirus type 16 E7 gene encodes transactivation and
RT transformation functions similar to those of adenovirus E1A.";
RL Cell 53:539-547(1988).
RN [8]
RP INTERACTION WITH HUMAN RB1, AND FUNCTION.
RX PubMed=1316611; DOI=10.1073/pnas.89.10.4549;
RA Chellappan S., Kraus V.B., Kroger B., Munger K., Howley P.M., Phelps W.C.,
RA Nevins J.R.;
RT "Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7
RT protein share the capacity to disrupt the interaction between transcription
RT factor E2F and the retinoblastoma gene product.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:4549-4553(1992).
RN [9]
RP INTERACTION WITH HUMAN CHD4, IDENTIFICATION IN A COMPLEX WITH HUMAN HDAC1
RP AND CHD4, AND MUTAGENESIS OF LEU-67; 82-LEU-LEU-83 AND CYS-91.
RX PubMed=10228159; DOI=10.1093/emboj/18.9.2449;
RA Brehm A., Nielsen S.J., Miska E.A., McCance D.J., Reid J.L.,
RA Bannister A.J., Kouzarides T.;
RT "The E7 oncoprotein associates with Mi2 and histone deacetylase activity to
RT promote cell growth.";
RL EMBO J. 18:2449-2458(1999).
RN [10]
RP SUBUNIT.
RX PubMed=11123931; DOI=10.1021/bi002111g;
RA Clements A., Johnston K., Mazzarelli J.M., Ricciardi R.P., Marmorstein R.;
RT "Oligomerization properties of the viral oncoproteins adenovirus E1A and
RT human papillomavirus E7 and their complexes with the retinoblastoma
RT protein.";
RL Biochemistry 39:16033-16045(2000).
RN [11]
RP FUNCTION.
RX PubMed=11080488; DOI=10.1006/viro.2000.0584;
RA Barnard P., Payne E., McMillan N.A.;
RT "The human papillomavirus E7 protein is able to inhibit the antiviral and
RT anti-growth functions of interferon-alpha.";
RL Virology 277:411-419(2000).
RN [12]
RP INTERACTION WITH HOST EP300.
RX PubMed=12970734; DOI=10.1038/sj.onc.1206896;
RA Bernat A., Avvakumov N., Mymryk J.S., Banks L.;
RT "Interaction between the HPV E7 oncoprotein and the transcriptional
RT coactivator p300.";
RL Oncogene 22:7871-7881(2003).
RN [13]
RP SUBUNIT.
RX PubMed=15035602; DOI=10.1021/bi036037o;
RA Alonso L.G., Garcia-Alai M.M., Smal C., Centeno J.M., Iacono R.,
RA Castano E., Gualfetti P., de Prat-Gay G.;
RT "The HPV16 E7 viral oncoprotein self-assembles into defined spherical
RT oligomers.";
RL Biochemistry 43:3310-3317(2004).
RN [14]
RP INTERACTION WITH E2.
RX PubMed=16439535; DOI=10.1128/jvi.80.4.1787-1797.2006;
RA Gammoh N., Grm H.S., Massimi P., Banks L.;
RT "Regulation of human papillomavirus type 16 E7 activity through direct
RT protein interaction with the E2 transcriptional activator.";
RL J. Virol. 80:1787-1797(2006).
RN [15]
RP DOMAIN.
RX PubMed=17715947; DOI=10.1021/bi7007917;
RA Garcia-Alai M.M., Alonso L.G., de Prat-Gay G.;
RT "The N-terminal module of HPV16 E7 is an intrinsically disordered domain
RT that confers conformational and recognition plasticity to the
RT oncoprotein.";
RL Biochemistry 46:10405-10412(2007).
RN [16]
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 [17]
RP SUBCELLULAR LOCATION, AND NUCLEAR EXPORT SIGNAL.
RX PubMed=18996550; DOI=10.1016/j.virol.2008.09.037;
RA Knapp A.A., McManus P.M., Bockstall K., Moroianu J.;
RT "Identification of the nuclear localization and export signals of high risk
RT HPV16 E7 oncoprotein.";
RL Virology 383:60-68(2009).
RN [18]
RP ROLE AS ANTIGEN IN HEAD AND NECK SQUAMOUS CELL CARCINOMA.
RX PubMed=33208941; DOI=10.1038/s41586-020-2931-3;
RA Wieland A., Patel M.R., Cardenas M.A., Eberhardt C.S., Hudson W.H.,
RA Obeng R.C., Griffith C.C., Wang X., Chen Z.G., Kissick H.T., Saba N.F.,
RA Ahmed R.;
RT "Defining HPV-specific B cell responses in patients with head and neck
RT cancer.";
RL Nature 597:274-278(2021).
RN [19]
RP ROLE AS ANTIGEN IN HEAD AND NECK SQUAMOUS CELL CARCINOMA.
RX PubMed=34471285; DOI=10.1038/s41586-021-03862-z;
RA Eberhardt C.S., Kissick H.T., Patel M.R., Cardenas M.A., Prokhnevska N.,
RA Obeng R.C., Nasti T.H., Griffith C.C., Im S.J., Wang X., Shin D.M.,
RA Carrington M., Chen Z.G., Sidney J., Sette A., Saba N.F., Wieland A.,
RA Ahmed R.;
RT "Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck
RT cancer.";
RL Nature 597:279-284(2021).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 21-29.
RX PubMed=25917549; DOI=10.1101/gad.257568.114;
RA Guiley K.Z., Liban T.J., Felthousen J.G., Ramanan P., Litovchick L.,
RA Rubin S.M.;
RT "Structural mechanisms of DREAM complex assembly and regulation.";
RL Genes Dev. 29:961-974(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). {ECO:0000255|HAMAP-
CC Rule:MF_04004, ECO:0000269|PubMed:11080488, ECO:0000269|PubMed:1316611,
CC ECO:0000269|PubMed:2836062}.
CC -!- SUBUNIT: Homodimer (PubMed:11123931). Homooligomer (PubMed:15035602).
CC Interacts with host RB1; this interaction induces dissociation of RB1-
CC E2F1 complex thereby disrupting RB1 activity (PubMed:1316611).
CC Interacts with host EP300; this interaction represses EP300
CC transcriptional activity (PubMed:12970734). Forms a complex with CHD4
CC and HDAC1, thereby altering the action of host histone deacetylation. A
CC similar complex involving E7, CHD4 and HDAC2 may also form
CC (PubMed:10228159). Interacts with protein E2; this interaction inhibits
CC E7 oncogenic activity (PubMed:16439535). {ECO:0000255|HAMAP-
CC Rule:MF_04004, ECO:0000269|PubMed:10228159,
CC ECO:0000269|PubMed:11123931, ECO:0000269|PubMed:12970734,
CC ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:15035602,
CC ECO:0000269|PubMed:16439535}.
CC -!- INTERACTION:
CC P03129; P20248: CCNA2; Xeno; NbExp=2; IntAct=EBI-866453, EBI-457097;
CC P03129; P24941: CDK2; Xeno; NbExp=2; IntAct=EBI-866453, EBI-375096;
CC P03129; O15111: CHUK; Xeno; NbExp=2; IntAct=EBI-866453, EBI-81249;
CC P03129; Q01094: E2F1; Xeno; NbExp=2; IntAct=EBI-866453, EBI-448924;
CC P03129; Q16254: E2F4; Xeno; NbExp=2; IntAct=EBI-866453, EBI-448943;
CC P03129; Q08050-1: FOXM1; Xeno; NbExp=3; IntAct=EBI-866453, EBI-866499;
CC P03129; P10914: IRF1; Xeno; NbExp=3; IntAct=EBI-866453, EBI-1055781;
CC P03129; Q92831: KAT2B; Xeno; NbExp=3; IntAct=EBI-866453, EBI-477430;
CC P03129; P01106: MYC; Xeno; NbExp=2; IntAct=EBI-866453, EBI-447544;
CC P03129; P67775: PPP2CA; Xeno; NbExp=3; IntAct=EBI-866453, EBI-712311;
CC P03129; P30153: PPP2R1A; Xeno; NbExp=3; IntAct=EBI-866453, EBI-302388;
CC P03129; P06400: RB1; Xeno; NbExp=23; IntAct=EBI-866453, EBI-491274;
CC P03129; P28749: RBL1; Xeno; NbExp=4; IntAct=EBI-866453, EBI-971402;
CC P03129; O15304: SIVA1; Xeno; NbExp=4; IntAct=EBI-866453, EBI-520756;
CC P03129; Q14188: TFDP2; Xeno; NbExp=2; IntAct=EBI-866453, EBI-752268;
CC P03129; Q5T4S7: UBR4; Xeno; NbExp=5; IntAct=EBI-866453, EBI-1995940;
CC P03129; P51784: USP11; Xeno; NbExp=6; IntAct=EBI-866453, EBI-306876;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04004,
CC ECO:0000269|PubMed:18996550, ECO:0000269|PubMed:3033296}. Host nucleus
CC {ECO:0000255|HAMAP-Rule:MF_04004, ECO:0000269|PubMed:18996550}.
CC Note=Predominantly found in the host nucleus. {ECO:0000255|HAMAP-
CC Rule:MF_04004, ECO:0000269|PubMed:18996550}.
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 ECO:0000269|PubMed:17715947}.
CC -!- PTM: Highly phosphorylated. {ECO:0000255|HAMAP-Rule:MF_04004,
CC ECO:0000269|PubMed:3033296}.
CC -!- MISCELLANEOUS: HPV16, in comparison to HPV types 6 and 11, is more
CC often associated with malignant genital cancers in humans.
CC -!- MISCELLANEOUS: Part of the antigens expressed and presented within HPV-
CC positive head and neck tumors. {ECO:0000269|PubMed:33208941,
CC ECO:0000269|PubMed:34471285}.
CC -!- SIMILARITY: Belongs to the papillomaviridae E7 protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04004}.
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DR EMBL; K02718; AAA46940.1; -; Genomic_DNA.
DR EMBL; D00735; BAA00633.1; -; Genomic_DNA.
DR EMBL; AF003020; AAB70737.1; -; Genomic_DNA.
DR EMBL; AF003023; AAB70740.1; -; Genomic_DNA.
DR EMBL; AF003024; AAB70741.1; -; Genomic_DNA.
DR EMBL; AF003025; AAB70742.1; -; Genomic_DNA.
DR EMBL; AF003026; AAB70743.1; -; Genomic_DNA.
DR EMBL; U76411; AAB18962.1; -; Genomic_DNA.
DR EMBL; U76412; AAB18963.1; -; Genomic_DNA.
DR EMBL; U76413; AAB18964.1; -; Genomic_DNA.
DR EMBL; AF536179; AAQ10713.1; -; Genomic_DNA.
DR EMBL; AF536180; AAQ10721.1; -; Genomic_DNA.
DR PIR; A03688; W7WLHS.
DR RefSeq; NP_041326.1; NC_001526.4.
DR PDB; 4YOZ; X-ray; 2.25 A; B=21-29.
DR PDB; 6APN; X-ray; 2.22 A; A/B=82-90.
DR PDBsum; 4YOZ; -.
DR PDBsum; 6APN; -.
DR BMRB; P03129; -.
DR SMR; P03129; -.
DR BioGRID; 4263558; 183.
DR DIP; DIP-1090N; -.
DR IntAct; P03129; 120.
DR MINT; P03129; -.
DR ChEMBL; CHEMBL4630866; -.
DR iPTMnet; P03129; -.
DR PRIDE; P03129; -.
DR ABCD; P03129; 4 sequenced antibodies.
DR DNASU; 1489079; -.
DR GeneID; 1489079; -.
DR KEGG; vg:1489079; -.
DR Proteomes; UP000009251; Genome.
DR Proteomes; UP000106302; Genome.
DR Proteomes; UP000115181; 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:0046870; F:cadmium ion binding; IDA:CAFA.
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:0140297; F:DNA-binding transcription factor binding; IDA:CAFA.
DR GO; GO:0019904; F:protein domain specific binding; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IDA:CAFA.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-UniRule.
DR GO; GO:0019056; P:modulation by virus of host transcription; IMP:UniProtKB.
DR GO; GO:1990216; P:positive regulation by symbiont of host transcription; IMP:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0039650; P:suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0039560; P:suppression by virus of host JAK-STAT cascade via inhibition of host IRF9 activity; IDA:UniProtKB.
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 DisProt; DP00024; -.
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..98
FT /note="Protein E7"
FT /id="PRO_0000133414"
FT ZN_FING 58..94
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04004"
FT REGION 1..40
FT /note="E7 terminal domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04004,
FT ECO:0000269|PubMed:17715947"
FT MOTIF 22..26
FT /note="LXCXE motif; interaction with host RB1 and
FT TMEM173/STING"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04004"
FT MOTIF 76..84
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04004,
FT ECO:0000269|PubMed:18996550"
FT MUTAGEN 67
FT /note="L->R: Complete loss of interaction with HDAC1 and
FT transformation ability."
FT /evidence="ECO:0000269|PubMed:10228159"
FT MUTAGEN 82..83
FT /note="LL->RR: Complete loss of interaction with HDAC1 and
FT transformation ability."
FT /evidence="ECO:0000269|PubMed:10228159"
FT MUTAGEN 91
FT /note="C->G: Complete loss of interaction with HDAC1 and
FT transformation ability."
FT /evidence="ECO:0000269|PubMed:10228159"
SQ SEQUENCE 98 AA; 11022 MW; 9BD612534CD2C9EB CRC64;
MHGDTPTLHE YMLDLQPETT DLYCYEQLND SSEEEDEIDG PAGQAEPDRA HYNIVTFCCK
CDSTLRLCVQ STHVDIRTLE DLLMGTLGIV CPICSQKP
