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Protein

Regulatory protein E2

Gene

E2

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 the initiation of viral DNA replication. A dimer of E2 interacts with a dimer of E1 in order to improve specificity of E1 DNA binding activity. Once the complex recognizes and binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also regulates viral transcription through binding to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory regions of the viral genome. Activates or represses transcription depending on E2RE's position with regards to proximal promoter elements including the TATA-box. Repression occurs by sterically hindering the assembly of the transcription initiation complex.UniRule annotation6 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

DNA replication, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Regulatory protein E2UniRule annotation
Gene namesi
Name:E2UniRule 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

GO - Cellular componenti

  • host cell nucleus Source: UniProtKB-SubCell
  • host cytoskeleton Source: CACAO
Complete GO annotation...

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi292 – 2921K → R: Complete loss of sumoylation. 1 Publication

Chemistry

ChEMBLiCHEMBL4656.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 365365Regulatory protein E2PRO_0000133195Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei243 – 2431Phosphoserine; by host1 Publication
Cross-linki292 – 292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)UniRule annotation1 Publication

Post-translational modificationi

Phosphorylated. Phosphorylation at Ser-243 mediates binding to host Brd4 and is required for host chromosome binding.UniRule annotation2 Publications
Sumoylation plays a regulatory role in E2 transcriptional activity.UniRule annotation1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Expressioni

Keywords - Developmental stagei

Early protein

Interactioni

Subunit structurei

Binds DNA as homodimer. Interacts with protein E1; this interaction greatly increases E1 DNA-binding activity. Interacts with protein L1; this interaction enhances E2-dependent replication and transcription activation. Interacts with protein L2; this interaction inhibits E2 transcriptional activity but not DNA replication function E2. Interacts with protein E7; this interaction inhibits E7 oncogenic activity. Interacts with host TAF1; this interaction modulates E2-dependent transcriptional regulation. Interacts with host BRD4; this interaction mediates E2 transcriptional activation function. Additionally, the interaction with host BRD4 on mitotic chromosomes mediates tethering of the viral genome. Interacts with host TOPBP1; this interaction is required for optimal viral DNA replication.UniRule annotation9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BRD4O608853EBI-1779322,EBI-723869From a different organism.
CEBPBP176762EBI-1779322,EBI-969696From a different organism.
CPSF3P791012EBI-1779322,EBI-7894416From a different organism.
CPSF4O191373EBI-1779322,EBI-7894441From a different organism.
E1P031143EBI-1779322,EBI-7387308
Rep68P031322EBI-1779322,EBI-7387242From a different organism.
TOPBP1Q925472EBI-1779322,EBI-308302From a different organism.

Protein-protein interaction databases

DIPiDIP-44574N.
IntActiP03120. 19 interactions.
MINTiMINT-95621.

Chemistry

BindingDBiP03120.

Structurei

Secondary structure

365
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi1 – 2121Combined sources
Helixi26 – 4823Combined sources
Beta strandi52 – 543Combined sources
Helixi62 – 8322Combined sources
Turni86 – 894Combined sources
Turni94 – 974Combined sources
Helixi99 – 1024Combined sources
Beta strandi104 – 1063Combined sources
Beta strandi111 – 12212Combined sources
Beta strandi128 – 14114Combined sources
Beta strandi144 – 1485Combined sources
Beta strandi154 – 1618Combined sources
Beta strandi164 – 1707Combined sources
Helixi171 – 1788Combined sources
Beta strandi180 – 1823Combined sources
Beta strandi185 – 1917Combined sources
Beta strandi286 – 2938Combined sources
Helixi295 – 30511Combined sources
Helixi306 – 3116Combined sources
Beta strandi313 – 3153Combined sources
Beta strandi331 – 3366Combined sources
Helixi340 – 34910Combined sources
Beta strandi356 – 3638Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BY9X-ray2.20A285-365[»]
1DTOX-ray1.90A1-201[»]
1R8PNMR-A/B286-365[»]
1ZZFNMR-A/B286-365[»]
2NNUX-ray1.59A1-201[»]
2Q79X-ray1.80A285-365[»]
3MI7X-ray2.20X283-365[»]
ProteinModelPortaliP03120.
SMRiP03120. Positions 1-200, 286-365.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03120.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 200200Transactivation domainUniRule annotation1 PublicationAdd
BLAST
Regioni285 – 36581DNA-binding domainUniRule annotation1 PublicationAdd
BLAST

Sequence similaritiesi

Belongs to the papillomaviridae E2 protein family.UniRule annotation

Family and domain databases

Gene3Di2.170.200.10. 1 hit.
3.30.70.330. 1 hit.
HAMAPiMF_04001. PPV_E2.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000427. Papillomavirus_E2_C.
IPR001866. Papillomavirus_E2_N.
[Graphical view]
PfamiPF00511. PPV_E2_C. 1 hit.
PF00508. PPV_E2_N. 1 hit.
[Graphical view]
ProDomiPD000672. E2_early_recog_prot_C. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF51332. SSF51332. 1 hit.
SSF54957. SSF54957. 1 hit.

Sequencei

Sequence statusi: Complete.

P03120-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METLCQRLNV CQDKILTHYE NDSTDLRDHI DYWKHMRLEC AIYYKAREMG
60 70 80 90 100
FKHINHQVVP TLAVSKNKAL QAIELQLTLE TIYNSQYSNE KWTLQDVSLE
110 120 130 140 150
VYLTAPTGCI KKHGYTVEVQ FDGDICNTMH YTNWTHIYIC EEASVTVVEG
160 170 180 190 200
QVDYYGLYYV HEGIRTYFVQ FKDDAEKYSK NKVWEVHAGG QVILCPTSVF
210 220 230 240 250
SSNEVSSPEI IRQHLANHPA ATHTKAVALG TEETQTTIQR PRSEPDTGNP
260 270 280 290 300
CHTTKLLHRD SVDSAPILTA FNSSHKGRIN CNSNTTPIVH LKGDANTLKC
310 320 330 340 350
LRYRFKKHCT LYTAVSSTWH WTGHNVKHKS AIVTLTYDSE WQRDQFLSQV
360
KIPKTITVST GFMSI
Length:365
Mass (Da):41,825
Last modified:July 21, 1986 - v1
Checksum:i27581F82B246E112
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti77 – 771L → P in AAQ10715 (Ref. 2) Curated
Sequence conflicti210 – 2101I → T in AAQ10715 (Ref. 2) Curated
Sequence conflicti219 – 2191P → S in AAQ10715 (Ref. 2) Curated
Sequence conflicti310 – 3101T → K in AAQ10715 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02718 Genomic DNA. Translation: AAA46941.1.
AF536179 Genomic DNA. Translation: AAQ10715.1.
PIRiA03669. W2WLHS.
RefSeqiNP_041328.1. NC_001526.2.

Genome annotation databases

GeneIDi1489080.
KEGGivg:1489080.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02718 Genomic DNA. Translation: AAA46941.1.
AF536179 Genomic DNA. Translation: AAQ10715.1.
PIRiA03669. W2WLHS.
RefSeqiNP_041328.1. NC_001526.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BY9X-ray2.20A285-365[»]
1DTOX-ray1.90A1-201[»]
1R8PNMR-A/B286-365[»]
1ZZFNMR-A/B286-365[»]
2NNUX-ray1.59A1-201[»]
2Q79X-ray1.80A285-365[»]
3MI7X-ray2.20X283-365[»]
ProteinModelPortaliP03120.
SMRiP03120. Positions 1-200, 286-365.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-44574N.
IntActiP03120. 19 interactions.
MINTiMINT-95621.

Chemistry

BindingDBiP03120.
ChEMBLiCHEMBL4656.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1489080.
KEGGivg:1489080.

Miscellaneous databases

EvolutionaryTraceiP03120.
PROiP03120.

Family and domain databases

Gene3Di2.170.200.10. 1 hit.
3.30.70.330. 1 hit.
HAMAPiMF_04001. PPV_E2.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000427. Papillomavirus_E2_C.
IPR001866. Papillomavirus_E2_N.
[Graphical view]
PfamiPF00511. PPV_E2_C. 1 hit.
PF00508. PPV_E2_N. 1 hit.
[Graphical view]
ProDomiPD000672. E2_early_recog_prot_C. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF51332. SSF51332. 1 hit.
SSF54957. SSF54957. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "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 European German 131.
  3. "Transcriptional trans-activation by the human papillomavirus type 16 E2 gene product."
    Phelps W.C., Howley P.M.
    J. Virol. 61:1630-1638(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "Transient replication of human papillomavirus DNAs."
    Del Vecchio A.M., Romanczuk H., Howley P.M., Baker C.C.
    J. Virol. 66:5949-5958(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Characterization of human papillomavirus type 16 E2 protein and subdomains expressed in insect cells."
    Sanders C.M., Stern P.L., Maitland N.J.
    Virology 211:418-433(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION, DIMERIZATION.
  6. "Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2."
    Okoye A., Cordano P., Taylor E.R., Morgan I.M., Everett R., Campo M.S.
    Virus Res. 108:1-14(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH L2.
  7. "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 E7.
  8. "Bromodomain protein 4 mediates the papillomavirus E2 transcriptional activation function."
    Schweiger M.R., You J., Howley P.M.
    J. Virol. 80:4276-4285(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HOST BRD4.
  9. "TAF1 interacts with and modulates human papillomavirus 16 E2-dependent transcriptional regulation."
    Centeno F., Ramirez-Salazar E., Garcia-Villa E., Gariglio P., Garrido E.
    Intervirology 51:137-143(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST TAF1.
  10. "Modification of papillomavirus E2 proteins by the small ubiquitin-like modifier family members (SUMOs)."
    Wu Y.C., Roark A.A., Bian X.L., Wilson V.G.
    Virology 378:329-338(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUMOYLATION, MUTAGENESIS OF LYS-292, SUBCELLULAR LOCATION.
  11. "The human papillomavirus 16 E2 protein is stabilised in S phase."
    Johansson C., Graham S.V., Dornan E.S., Morgan I.M.
    Virology 394:194-199(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  12. "An interaction between human papillomavirus 16 E2 and TopBP1 is required for optimum viral DNA replication and episomal genome establishment."
    Donaldson M.M., Mackintosh L.J., Bodily J.M., Dornan E.S., Laimins L.A., Morgan I.M.
    J. Virol. 86:12806-12815(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOST TOPBP1.
  13. "Phosphorylation of HPV-16 E2 at serine 243 enables binding to Brd4 and mitotic chromosomes."
    Chang S.W., Liu W.C., Liao K.Y., Tsao Y.P., Hsu P.H., Chen S.L.
    PLoS ONE 9:E110882-E110882(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-243, FUNCTION, SUBCELLULAR LOCATION.
  14. "The human papillomavirus type 16 L1 protein directly interacts with E2 and enhances E2-dependent replication and transcription activation."
    Siddiqa A., Leon K.C., James C.D., Bhatti M.F., Roberts S., Parish J.L.
    J. Gen. Virol. 96:2274-2285(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PROTEIN L1, SUBCELLULAR LOCATION.
  15. "Failure to interact with Brd4 alters the ability of HPV16 E2 to regulate host genome expression and cellular movement."
    Gauson E.J., Wang X., Dornan E.S., Herzyk P., Bristol M., Morgan I.M.
    Virus Res. 211:1-8(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  16. "Expression, crystallization and preliminary X-ray analysis of the E2 transactivation domain from papillomavirus type 16."
    Burns J.E., Moroz O.V., Antson A.A., Sanders C.M., Wilson K.S., Maitland N.J.
    Acta Crystallogr. D 54:1471-1474(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-201, TRANSACTIVATION DOMAIN.
  17. "Crystal structure of the E2 DNA-binding domain from human papillomavirus type 16: implications for its DNA binding-site selection mechanism."
    Hegde R.S., Androphy E.J.
    J. Mol. Biol. 284:1479-1489(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 285-365, DIMERIZATION, DNA-BINDING DOMAIN.
  18. "Structure of the intact transactivation domain of the human papillomavirus E2 protein."
    Antson A.A., Burns J.E., Moroz O.V., Scott D.J., Sanders C.M., Bronstein I.B., Dodson G.G., Wilson K.S., Maitland N.J.
    Nature 403:805-809(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-201.
  19. "Solution structure of the HPV-16 E2 DNA binding domain, a transcriptional regulator with a dimeric beta-barrel fold."
    Nadra A.D., Eliseo T., Mok Y.K., Almeida C.L., Bycroft M., Paci M., de Prat-Gay G., Cicero D.O.
    J. Biomol. NMR 30:211-214(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 286-365.
  20. "Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association."
    Abbate E.A., Voitenleitner C., Botchan M.R.
    Mol. Cell 24:877-889(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 1-201, INTERACTION WITH HOST BRD4.
  21. "Increased stability and DNA site discrimination of 'single chain' variants of the dimeric beta-barrel DNA binding domain of the human papillomavirus E2 transcriptional regulator."
    Dellarole M., Sanchez I.E., Freire E., de Prat-Gay G.
    Biochemistry 46:12441-12450(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 285-365.
  22. "Design and characterization of an enhanced repressor of human papillomavirus E2 protein."
    Bose K., Meinke G., Bohm A., Baleja J.D.
    FASEB J. 25:2354-2361(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 283-365.

Entry informationi

Entry nameiVE2_HPV16
AccessioniPrimary (citable) accession number: P03120
Secondary accession number(s): Q71BI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: May 11, 2016
This is version 133 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.