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Protein

Protein E7

Gene

E7

Organism
Human papillomavirus type 16
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E7 protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Interferes with host histone deacetylation mediated by HDAC1 and HDAC2, leading to transcription activation. Plays also a role in the inhibition of both antiviral and antiproliferative functions of host inteferon alpha.UniRule annotation3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri58 – 9437UniRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • modulation by virus of host G1/S transition checkpoint Source: UniProtKB-KW
  • positive regulation of actin filament polymerization Source: UniProtKB
  • positive regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
  • positive regulation of wound healing, spreading of epidermal cells Source: UniProtKB
  • regulation of wound healing, spreading of epidermal cells Source: UniProtKB
  • suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • suppression by virus of host IRF9 activity Source: UniProtKB
  • suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

G1/S host cell cycle checkpoint dysregulation by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Modulation of host cell cycle by virus, Transcription, Transcription regulation, Viral immunoevasion

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Protein E7UniRule annotation
Gene namesi
Name:E7UniRule annotation
OrganismiHuman papillomavirus type 16
Taxonomic identifieri333760 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stagePapillomaviridaeAlphapapillomavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000009251 Componenti: Genome

Subcellular locationi

  • Host cytoplasm UniRule annotation2 Publications
  • Host nucleus UniRule annotation1 Publication

  • Note: Predominantly found in the host nucleus.UniRule annotation1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi67 – 671L → R: Complete loss of interaction with HDAC1 and transformation ability. 1 Publication
Mutagenesisi82 – 832LL → RR: Complete loss of interaction with HDAC1 and transformation ability. 1 Publication
Mutagenesisi91 – 911C → G: Complete loss of interaction with HDAC1 and transformation ability. 1 Publication

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 9898Protein E7PRO_0000133414Add
BLAST

Post-translational modificationi

Highly phosphorylated.UniRule annotation1 Publication

PTM databases

iPTMnetiP03129.

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Homodimer (PubMed:11123931). Homooligomer (PubMed:15035602). Interacts with host RB1; this interaction induces dissociation of RB1-E2F1 complex thereby disrupting RB1 activity (PubMed:1316611). Interacts with host EP300; this interaction represses EP300 transcriptional activity (PubMed:12970734). Forms a complex with CHD4 and HDAC1, thereby altering the action of host histone deacetylation. A similar complex involving E7, CHD4 and HDAC2 may also form (PubMed:10228159). Interacts with protein E2; this interaction inhibits E7 oncogenic activity (PubMed:16439535).UniRule annotation6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CHUKO151112EBI-866453,EBI-81249From a different organism.
FOXM1Q08050-13EBI-866453,EBI-866499From a different organism.
IRF1P109143EBI-866453,EBI-1055781From a different organism.
KAT2BQ928313EBI-866453,EBI-477430From a different organism.
MYCP011062EBI-866453,EBI-447544From a different organism.
PPP2CAP677753EBI-866453,EBI-712311From a different organism.
PPP2R1AP301533EBI-866453,EBI-302388From a different organism.
RB1P0640021EBI-866453,EBI-491274From a different organism.
SIVA1O153044EBI-866453,EBI-520756From a different organism.
UBR4Q5T4S74EBI-866453,EBI-1995940From a different organism.
USP11P517846EBI-866453,EBI-306876From a different organism.

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi4263558. 5 interactions.
DIPiDIP-1090N.
IntActiP03129. 26 interactions.
MINTiMINT-87652.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4YOZX-ray2.25B21-29[»]
DisProtiDP00024.
ProteinModelPortaliP03129.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 4040DisorderedUniRule annotation1 PublicationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi22 – 265LXCXE motif; interaction with host RB1UniRule annotation
Motifi76 – 849Nuclear export signalUniRule annotation1 Publication

Sequence similaritiesi

Belongs to the papillomaviridae E7 protein family.UniRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri58 – 9437UniRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Family and domain databases

HAMAPiMF_04004. PPV_E7.
InterProiIPR000148. Papilloma_E7.
[Graphical view]
PfamiPF00527. E7. 1 hit.
[Graphical view]
PIRSFiPIRSF003407. Papvi_E7. 1 hit.

Sequencei

Sequence statusi: Complete.

P03129-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MHGDTPTLHE YMLDLQPETT DLYCYEQLND SSEEEDEIDG PAGQAEPDRA
60 70 80 90
HYNIVTFCCK CDSTLRLCVQ STHVDIRTLE DLLMGTLGIV CPICSQKP
Length:98
Mass (Da):11,022
Last modified:July 21, 1986 - v1
Checksum:i9BD612534CD2C9EB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02718 Genomic DNA. Translation: AAA46940.1.
D00735 Genomic DNA. Translation: BAA00633.1.
AF003020 Genomic DNA. Translation: AAB70737.1.
AF003023 Genomic DNA. Translation: AAB70740.1.
AF003024 Genomic DNA. Translation: AAB70741.1.
AF003025 Genomic DNA. Translation: AAB70742.1.
AF003026 Genomic DNA. Translation: AAB70743.1.
U76411 Genomic DNA. Translation: AAB18962.1.
U76412 Genomic DNA. Translation: AAB18963.1.
U76413 Genomic DNA. Translation: AAB18964.1.
AF536179 Genomic DNA. Translation: AAQ10713.1.
AF536180 Genomic DNA. Translation: AAQ10721.1.
PIRiA03688. W7WLHS.
RefSeqiNP_041326.1. NC_001526.2.

Genome annotation databases

GeneIDi1489079.
KEGGivg:1489079.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02718 Genomic DNA. Translation: AAA46940.1.
D00735 Genomic DNA. Translation: BAA00633.1.
AF003020 Genomic DNA. Translation: AAB70737.1.
AF003023 Genomic DNA. Translation: AAB70740.1.
AF003024 Genomic DNA. Translation: AAB70741.1.
AF003025 Genomic DNA. Translation: AAB70742.1.
AF003026 Genomic DNA. Translation: AAB70743.1.
U76411 Genomic DNA. Translation: AAB18962.1.
U76412 Genomic DNA. Translation: AAB18963.1.
U76413 Genomic DNA. Translation: AAB18964.1.
AF536179 Genomic DNA. Translation: AAQ10713.1.
AF536180 Genomic DNA. Translation: AAQ10721.1.
PIRiA03688. W7WLHS.
RefSeqiNP_041326.1. NC_001526.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4YOZX-ray2.25B21-29[»]
DisProtiDP00024.
ProteinModelPortaliP03129.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4263558. 5 interactions.
DIPiDIP-1090N.
IntActiP03129. 26 interactions.
MINTiMINT-87652.

PTM databases

iPTMnetiP03129.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1489079.
KEGGivg:1489079.

Family and domain databases

HAMAPiMF_04004. PPV_E7.
InterProiIPR000148. Papilloma_E7.
[Graphical view]
PfamiPF00527. E7. 1 hit.
[Graphical view]
PIRSFiPIRSF003407. Papvi_E7. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Expression of the human papillomavirus type 16 genome in SK-v cells, a line derived from a vulvar intraepithelial neoplasia."
    Schneider-Maunoury S., Pehau-Arnaudet G., Breitburd F., Orth G.
    J. Gen. Virol. 71:809-817(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Sequence variations and viral genomic state of human papillomavirus type 16 in penile carcinomas from Ugandan patients."
    Tornesello M.L., Buonaguro F.M., Meglio A., Buonaguro L., Beth-Giraldo E., Giraldo G.
    J. Gen. Virol. 78:2199-2208(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Major sequence variations in E7 gene of human papillomavirus type 16 from cervical cancerous and non-cancerous lesions of Korean women."
    Song Y.S., Kee S.H., Kim J.W., Park N.H., Kang S.B., Lee H.P.
    Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "Cloning and sequencing of non-European human papillomavirus (HPV) variant complete genomes from cervicovaginal cells by an overlapping PCR method."
    Terai M., Fu L., Ma Z., Burk R.D.
    Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: Isolate African 1 and Isolate European German 131.
  6. "The major human papillomavirus protein in cervical cancers is a cytoplasmic phosphoprotein."
    Smotkin D., Wettstein F.O.
    J. Virol. 61:1686-1689(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
  7. "The human papillomavirus type 16 E7 gene encodes transactivation and transformation functions similar to those of adenovirus E1A."
    Phelps W.C., Yee C.L., Munger K., Howley P.M.
    Cell 53:539-547(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product."
    Chellappan S., Kraus V.B., Kroger B., Munger K., Howley P.M., Phelps W.C., Nevins J.R.
    Proc. Natl. Acad. Sci. U.S.A. 89:4549-4553(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN RB1, FUNCTION.
  9. "The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth."
    Brehm A., Nielsen S.J., Miska E.A., McCance D.J., Reid J.L., Bannister A.J., Kouzarides T.
    EMBO J. 18:2449-2458(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN CHD4, IDENTIFICATION IN A COMPLEX WITH HUMAN HDAC1 AND CHD4, MUTAGENESIS OF LEU-67; 82-LEU-LEU-83 AND CYS-91.
  10. "Oligomerization properties of the viral oncoproteins adenovirus E1A and human papillomavirus E7 and their complexes with the retinoblastoma protein."
    Clements A., Johnston K., Mazzarelli J.M., Ricciardi R.P., Marmorstein R.
    Biochemistry 39:16033-16045(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  11. "The human papillomavirus E7 protein is able to inhibit the antiviral and anti-growth functions of interferon-alpha."
    Barnard P., Payne E., McMillan N.A.
    Virology 277:411-419(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300."
    Bernat A., Avvakumov N., Mymryk J.S., Banks L.
    Oncogene 22:7871-7881(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST EP300.
  13. "The HPV16 E7 viral oncoprotein self-assembles into defined spherical oligomers."
    Alonso L.G., Garcia-Alai M.M., Smal C., Centeno J.M., Iacono R., Castano E., Gualfetti P., de Prat-Gay G.
    Biochemistry 43:3310-3317(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  14. "Regulation of human papillomavirus type 16 E7 activity through direct protein interaction with the E2 transcriptional activator."
    Gammoh N., Grm H.S., Massimi P., Banks L.
    J. Virol. 80:1787-1797(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH E2.
  15. "The N-terminal module of HPV16 E7 is an intrinsically disordered domain that confers conformational and recognition plasticity to the oncoprotein."
    Garcia-Alai M.M., Alonso L.G., de Prat-Gay G.
    Biochemistry 46:10405-10412(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISORDERED REGION.
  16. "Interactions of SV40 large T antigen and other viral proteins with retinoblastoma tumour suppressor."
    Lee C., Cho Y.
    Rev. Med. Virol. 12:81-92(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  17. "Identification of the nuclear localization and export signals of high risk HPV16 E7 oncoprotein."
    Knapp A.A., McManus P.M., Bockstall K., Moroianu J.
    Virology 383:60-68(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL.
  18. "Structural mechanisms of DREAM complex assembly and regulation."
    Guiley K.Z., Liban T.J., Felthousen J.G., Ramanan P., Litovchick L., Rubin S.M.
    Genes Dev. 29:961-974(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 21-29.

Entry informationi

Entry nameiVE7_HPV16
AccessioniPrimary (citable) accession number: P03129
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 6, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

HPV16, in comparison to HPV types 6 and 11, is more often associated with malignant genital cancers in humans.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.