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Protein

Regulatory protein E2

Gene

E2

Organism
Human papillomavirus type 16
Status
Reviewed-Annotation score: -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

Miscellaneous

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processDNA replication, Transcription, Transcription regulation

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 stagePapillomaviridaeFirstpapillomavirinaeAlphapapillomavirus
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000106302 Componenti: Genome
  • UP000009251 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

  • host cell nucleus Source: UniProtKB-SubCell
  • host cytoskeleton Source: CACAO

Keywords - Cellular componenti

Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi292K → R: Complete loss of sumoylation. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4656

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001331951 – 365Regulatory protein E2Add BLAST365

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei243Phosphoserine; by host1 Publication1
Cross-linki292Glycyl 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

Proteomic databases

PRIDEiP03120

PTM databases

iPTMnetiP03120

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

Protein-protein interaction databases

BioGridi4263559, 1 interactor
DIPiDIP-44574N
IntActiP03120, 64 interactors
MINTiP03120

Chemistry databases

BindingDBiP03120

Structurei

Secondary structure

1365
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP03120
SMRiP03120
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03120

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 200Transactivation domainUniRule annotation1 PublicationAdd BLAST200
Regioni285 – 365DNA-binding domainUniRule annotation1 PublicationAdd BLAST81

Sequence similaritiesi

Belongs to the papillomaviridae E2 protein family.UniRule annotation

Phylogenomic databases

KOiK21811
OrthoDBiVOG0900010D

Family and domain databases

Gene3Di3.30.70.330, 1 hit
HAMAPiMF_04001 PPV_E2, 1 hit
InterProiView protein in InterPro
IPR035975 E2/EBNA1_C_sf
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR000427 Papillomavirus_E2_C
IPR001866 Papillomavirus_E2_N
IPR033668 Reg_prot_E2
IPR036050 Regulatory_protein_E2_N
PfamiView protein in Pfam
PF00511 PPV_E2_C, 1 hit
PF00508 PPV_E2_N, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD000672 E2_early_recog_prot_C, 1 hit
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)DescriptionActionsGraphical viewLength
Sequence conflicti77L → P in AAQ10715 (Ref. 2) Curated1
Sequence conflicti210I → T in AAQ10715 (Ref. 2) Curated1
Sequence conflicti219P → S in AAQ10715 (Ref. 2) Curated1
Sequence conflicti310T → K in AAQ10715 (Ref. 2) Curated1

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_001526.4

Genome annotation databases

GeneIDi1489080
KEGGivg:1489080

Similar proteinsi

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_001526.4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4263559, 1 interactor
DIPiDIP-44574N
IntActiP03120, 64 interactors
MINTiP03120

Chemistry databases

BindingDBiP03120
ChEMBLiCHEMBL4656

PTM databases

iPTMnetiP03120

Proteomic databases

PRIDEiP03120

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1489080
KEGGivg:1489080

Phylogenomic databases

KOiK21811
OrthoDBiVOG0900010D

Miscellaneous databases

EvolutionaryTraceiP03120
PROiPR:P03120

Family and domain databases

Gene3Di3.30.70.330, 1 hit
HAMAPiMF_04001 PPV_E2, 1 hit
InterProiView protein in InterPro
IPR035975 E2/EBNA1_C_sf
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR000427 Papillomavirus_E2_C
IPR001866 Papillomavirus_E2_N
IPR033668 Reg_prot_E2
IPR036050 Regulatory_protein_E2_N
PfamiView protein in Pfam
PF00511 PPV_E2_C, 1 hit
PF00508 PPV_E2_N, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD000672 E2_early_recog_prot_C, 1 hit
SUPFAMiSSF51332 SSF51332, 1 hit
SSF54957 SSF54957, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiVE2_HPV16
AccessioniPrimary (citable) accession number: P03120
Secondary accession number(s): Q71BI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 10, 2018
This is version 151 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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
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Main funding by: National Institutes of Health

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