UniProtKB - P03120 (VE2_HPV16)

BLAST

>sp|P03120|VE2_HPV16 Regulatory protein E2 OS=Human papillomavirus type 16 OX=333760 GN=E2 PE=1 SV=1
METLCQRLNVCQDKILTHYENDSTDLRDHIDYWKHMRLECAIYYKAREMGFKHINHQVVP
TLAVSKNKALQAIELQLTLETIYNSQYSNEKWTLQDVSLEVYLTAPTGCIKKHGYTVEVQ
FDGDICNTMHYTNWTHIYICEEASVTVVEGQVDYYGLYYVHEGIRTYFVQFKDDAEKYSK
NKVWEVHAGGQVILCPTSVFSSNEVSSPEIIRQHLANHPAATHTKAVALGTEETQTTIQR
PRSEPDTGNPCHTTKLLHRDSVDSAPILTAFNSSHKGRINCNSNTTPIVHLKGDANTLKC
LRYRFKKHCTLYTAVSSTWHWTGHNVKHKSAIVTLTYDSEWQRDQFLSQVKIPKTITVST
GFMSI

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History
Entry version 151 (10 Oct 2018)
Sequence version 1 (21 Jul 1986)
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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

DNA binding Source: UniProtKB-UniRule
DNA-binding transcription factor activity Source: UniProtKB-UniRule
nucleotide binding Source: UniProtKB-UniRule

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

DNA replication Source: UniProtKB-KW
regulation of DNA replication Source: UniProtKB-UniRule
transcription, DNA-templated Source: UniProtKB-UniRule
viral DNA genome replication Source: UniProtKB-UniRule

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Activator, DNA-binding, Repressor
Biological process	DNA replication, Transcription, Transcription regulation

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Regulatory protein E2UniRule annotation
Gene namesⁱ	Name:E2UniRule annotation
Organismⁱ	Human papillomavirus type 16
Taxonomic identifierⁱ	333760 [NCBI]
Taxonomic lineageⁱ	Viruses › dsDNA viruses, no RNA stage › Papillomaviridae › Firstpapillomavirinae › Alphapapillomavirus › Alphapapillomavirus 9
Virus hostⁱ	Homo sapiens (Human) [TaxID: 9606]
Proteomesⁱ	UP000106302 Componentⁱ: Genome UP000009251 Componentⁱ: Genome

Subcellular locationⁱ

Host nucleus
UniRule annotation
Manual assertion according to rulesⁱ
- HAMAP-Rule:MF_04001
4 Publications
Manual assertion based on experiment inⁱ
- Ref.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.
- Ref.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.
- Ref.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.
- Ref.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.

GO - Cellular componentⁱ

host cell nucleus Source: UniProtKB-SubCell
host cytoskeleton
Source: CACAO
Inferred from direct assayⁱ
- 15020762

View the complete GO annotation on QuickGO ...

Keywords - Cellular componentⁱ

Host nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	292	K → R: Complete loss of sumoylation. 1 Publication		1

Chemistry databases

ChEMBLⁱ	CHEMBL4656

ChEMBLⁱ

CHEMBL4656

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000133195	1 – 365	Regulatory protein E2Add BLAST		365

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	243	Phosphoserine; by host1 Publication		1
Cross-linkⁱ	292	Glycyl 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

PRIDEⁱ	P03120

PRIDEⁱ

P03120

PTM databases

iPTMnetⁱ	P03120

iPTMnetⁱ

P03120

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

With	Entry	#Exp.	IntAct	Notes
BRD4	O60885	4	EBI-1779322,EBI-723869	From Homo sapiens.
BRD4	O60885-1	2	EBI-1779322,EBI-9345088	From a different organism.
BTBD1	Q9H0C5	3	EBI-1779322,EBI-935503	From Homo sapiens.
CEBPB	P17676	2	EBI-1779322,EBI-969696	From Homo sapiens.
CPSF3	P79101	2	EBI-1779322,EBI-7894416	From Bos taurus.
CPSF4	O19137	3	EBI-1779322,EBI-7894441	From Bos taurus.
E1	P03114	3	EBI-1779322,EBI-7387308
HOXC9	P31274	3	EBI-1779322,EBI-1779423	From Homo sapiens.
NR4A1	P22736	3	EBI-1779322,EBI-721550	From Homo sapiens.
Rep68	P03132	2	EBI-1779322,EBI-7387242	From Adeno-associated virus 2 (isolate Srivastava/1982).
TOPBP1	Q92547	2	EBI-1779322,EBI-308302	From Homo sapiens.

Protein-protein interaction databases

BioGridⁱ	4263559, 1 interactor
Database of interacting proteins More...DIPⁱ	DIP-44574N
IntActⁱ	P03120, 64 interactors
Molecular INTeraction database More...MINTⁱ	P03120

Chemistry databases

BindingDBⁱ

P03120

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	1 – 21	Combined sources	21
Helixⁱ	26 – 48	Combined sources	23
Beta strandⁱ	52 – 54	Combined sources	3
Helixⁱ	62 – 83	Combined sources	22
Turnⁱ	86 – 89	Combined sources	4
Turnⁱ	94 – 97	Combined sources	4
Helixⁱ	99 – 103	Combined sources	5
Beta strandⁱ	104 – 106	Combined sources	3
Beta strandⁱ	110 – 121	Combined sources	12
Beta strandⁱ	127 – 141	Combined sources	15
Beta strandⁱ	144 – 148	Combined sources	5
Beta strandⁱ	154 – 161	Combined sources	8
Beta strandⁱ	164 – 170	Combined sources	7
Helixⁱ	171 – 178	Combined sources	8
Beta strandⁱ	180 – 182	Combined sources	3
Beta strandⁱ	184 – 190	Combined sources	7
Beta strandⁱ	286 – 293	Combined sources	8
Helixⁱ	295 – 305	Combined sources	11
Helixⁱ	306 – 311	Combined sources	6
Beta strandⁱ	313 – 315	Combined sources	3
Beta strandⁱ	331 – 336	Combined sources	6
Helixⁱ	340 – 349	Combined sources	10
Beta strandⁱ	356 – 363	Combined sources	8

Show more details

3D structure databases

ProteinModelPortalⁱ	P03120
SMRⁱ	P03120
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ

P03120

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	1 – 200	Transactivation domainUniRule annotation1 PublicationAdd BLAST		200
Regionⁱ	285 – 365	DNA-binding domainUniRule annotation1 PublicationAdd BLAST		81

Sequence similaritiesⁱ

Belongs to the papillomaviridae E2 protein family.UniRule annotation

Phylogenomic databases

KEGG Orthology (KO) More...KOⁱ	K21811
Database of Orthologous Groups More...OrthoDBⁱ	VOG0900010D

Family and domain databases

Gene3Dⁱ	3.30.70.330, 1 hit
HAMAPⁱ	MF_04001 PPV_E2, 1 hit
InterProⁱ	View 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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00511 PPV_E2_C, 1 hit PF00508 PPV_E2_N, 1 hit
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD000672 E2_early_recog_prot_C, 1 hit
SUPFAMⁱ	SSF51332 SSF51332, 1 hit SSF54957 SSF54957, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

P03120-1 [UniParc]FASTA Add 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

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	77	L → P in AAQ10715 (Ref. 2) Curated	1
Sequence conflictⁱ	210	I → T in AAQ10715 (Ref. 2) Curated	1
Sequence conflictⁱ	219	P → S in AAQ10715 (Ref. 2) Curated	1
Sequence conflictⁱ	310	T → K in AAQ10715 (Ref. 2) Curated	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	K02718 Genomic DNA Translation: AAA46941.1 AF536179 Genomic DNA Translation: AAQ10715.1
PIRⁱ	A03669 W2WLHS
NCBI Reference Sequences More...RefSeqⁱ	NP_041328.1, NC_001526.4

Genome annotation databases

GeneIDⁱ	1489080
KEGGⁱ	vg:1489080

Protein	Similar proteins		Species	Score	Length	Source
P03120	Regulatory protein E2		HPV16		365	UniRef100_P03120
Regulatory protein E2		Alphapapillomavirus 9		365
Regulatory protein E2		Human papillomavirus		365
E2 protein (Fragment)		HPV16		204
E2 protein (Fragment)		HPV16		204
+1

Protein	Similar proteins		Species	Score	Length	Source
P03120	Regulatory protein E2		HPV16		365	UniRef90_P03120
Regulatory protein E2		Alphapapillomavirus 9		365
Regulatory protein E2		Human papillomavirus		365
E2 (Early) protein, N terminal		CHLTH		365
E2 protein (Fragment)		HPV16		204
+754

Protein	Similar proteins		Species	Score	Length	Source
P03120	Regulatory protein E2		HPV35		367	UniRef50_P03120
Regulatory protein E2	)	HPV31		372
Regulatory protein E2		HPV58		358
Regulatory protein E2		HPV16		365
Regulatory protein E2		Alphapapillomavirus 9		365
+897

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
PIRⁱ	A03669 W2WLHS
RefSeqⁱ	NP_041328.1, NC_001526.4

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1BY9	X-ray	2.20	A	285-365	[»]
	1DTO	X-ray	1.90	A	1-201	[»]
	1R8P	NMR	-	A/B	286-365	[»]
	1ZZF	NMR	-	A/B	286-365	[»]
	2NNU	X-ray	1.59	A	1-201	[»]
	2Q79	X-ray	1.80	A	285-365	[»]
	3MI7	X-ray	2.20	X	283-365	[»]
ProteinModelPortalⁱ	P03120
SMRⁱ	P03120
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	4263559, 1 interactor
DIPⁱ	DIP-44574N
IntActⁱ	P03120, 64 interactors
MINTⁱ	P03120

Chemistry databases

BindingDBⁱ	P03120
ChEMBLⁱ	CHEMBL4656

PTM databases

iPTMnetⁱ	P03120

iPTMnetⁱ

P03120

Proteomic databases

PRIDEⁱ	P03120

PRIDEⁱ

P03120

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

GeneIDⁱ	1489080
KEGGⁱ	vg:1489080

Phylogenomic databases

KOⁱ	K21811
OrthoDBⁱ	VOG0900010D

Miscellaneous databases

EvolutionaryTraceⁱ	P03120
Protein Ontology More...PROⁱ	PR:P03120

Family and domain databases

Gene3Dⁱ	3.30.70.330, 1 hit
HAMAPⁱ	MF_04001 PPV_E2, 1 hit
InterProⁱ	View 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
Pfamⁱ	View protein in Pfam PF00511 PPV_E2_C, 1 hit PF00508 PPV_E2_N, 1 hit
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD000672 E2_early_recog_prot_C, 1 hit
SUPFAMⁱ	SSF51332 SSF51332, 1 hit SSF54957 SSF54957, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	VE2_HPV16
Accessionⁱ	P03120Primary (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:	October 10, 2018
	This is version 151 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Viral Protein Annotation Program

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UniParc

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UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P03120 (VE2_HPV16)

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Regulatory protein E2

E2

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Keywords - Developmental stagei

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Phylogenomic databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Keywords - Developmental stageⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ