P03129 (VE7_HPV16) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein E7

Gene names

Name:

E7

Organism

Human papillomavirus type 16 [Reference proteome]

Taxonomic identifier

333760 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Papillomaviridae › Alphapapillomavirus › Alphapapillomavirus 9

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	98 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E7 protein has both transforming and trans-activating activities. Disrupts the function of host retinoblastoma protein RB1/pRb, which is a key regulator of the cell cycle. Induces the disassembly of the E2F1 transcription factors from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. Interferes with histone deacetylation mediated by HDAC1 and HDAC2, leading to activation of transcription By similarity. Ref.6
Subunit structure	Homodimer. Homooligomer. Interaction with host RB1 induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting RB1's activity. Binds to CHD3 through its zinc-finger domain. Forms a complex with CHD3 and HDAC1, thereby altering the action of host histone deacetylation. A similar complex involving E7, CHD3 and HDAC2 might also form. Interacts with E2; this interaction inhibits E7 oncogenic activity. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Miscellaneous	HPV16, in comparison to HPV types 6 and 11, is more often associated with malignant genital cancers in humans.
Sequence similarities	Belongs to the papillomaviridae E7 protein family.

Ontologies

Keywords
Biological process	G1/S host cell cycle checkpoint dysregulation by virus Host gene expression shutoff by virus Host transcription shutoff by virus Host-virus interaction Inhibition of host IRF9 by virus Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Inhibition of host transcription initiation by virus Modulation of host cell cycle by virus Transcription Transcription regulation Viral immunoevasion
Developmental stage	Early protein
Disease	Oncogene
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	modulation by virus of host G1/S transition checkpoint Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host DNA-dependent transcription, initiation Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host IRF9 activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FOXM1	Q08050-1	3	EBI-866453,EBI-866499	From a different organism.
USP11	P51784	6	EBI-866453,EBI-306876	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 98	98	Protein E7		PRO_0000133414
Regions
	Zinc finger	58 – 94	37	Potential
	Region	1 – 40	40	Disordered Potential
	Region	22 – 26	5	Interaction with RB1 Potential
Experimental info
	Mutagenesis	67	1	L → R: Complete loss of interaction with HDAC1 and transformation ability. Ref.8
	Mutagenesis	82 – 83	2	LL → RR: Complete loss of interaction with HDAC1 and transformation ability.
	Mutagenesis	91	1	C → G: Complete loss of interaction with HDAC1 and transformation ability. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P03129 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 9BD612534CD2C9EB	FASTA	98	11,022
	10 20 30 40 50 60 MHGDTPTLHE YMLDLQPETT DLYCYEQLND SSEEEDEIDG PAGQAEPDRA HYNIVTFCCK 70 80 90 CDSTLRLCVQ STHVDIRTLE DLLMGTLGIV CPICSQKP

References

[1]	"Human papillomavirus type 16 DNA sequence." Seedorf K., Krammer G., Durst M., Suhai S., Rowekamp W.G. Virology 145:181-185(1985) [PubMed] [Europe PMC] [Abstract] 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 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.
[7]	"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.
[8]	"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 CHD3, IDENTIFICATION IN A COMPLEX WITH HUMAN HDAC1 AND CHD3, MUTAGENESIS OF LEU-67; 82-LEU-LEU-83 AND CYS-91.
[9]	"Translational regulation of human papillomavirus type 16 E7 mRNA by the peptide SEQIKA, shared by rabbit alpha(1)-globin and human cytokeratin 7." Kanduc D. J. Virol. 76:7040-7048(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN KRT7.
[10]	"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.
[11]	"Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600." Huh K.-W., DeMasi J., Ogawa H., Nakatani Y., Howley P.M., Muenger K. Proc. Natl. Acad. Sci. U.S.A. 102:11492-11497(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN ZUBR1.
[12]	"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.
[13]	"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.
[14]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
PIR	W7WLHS. A03688.
RefSeq	NP_041326.1. NC_001526.2.
3D structure databases
DisProt	DP00024.
ProteinModelPortal	P03129.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-1090N.
IntAct	P03129. 3 interactions.
MINT	MINT-87652.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	1489079.
Family and domain databases
InterPro	IPR000148. Papilloma_E7. [Graphical view]
Pfam	PF00527. E7. 1 hit. [Graphical view]
PIRSF	PIRSF003407. Papvi_E7. 1 hit.
ProtoNet	Search...

Entry information

Entry name

VE7_HPV16

Accession

Primary (citable) accession number: P03129

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 29, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program