P03191 (EAD_EBVB9) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA polymerase processivity factor BMRF1

Alternative name(s):
Early antigen protein D
Short name=EA-D
Polymerase accessory subunit

Gene names

ORF Names:

BMRF1

Organism

Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4)

Taxonomic identifier

10377 [NCBI]

Taxonomic lineage

Viruses › dsDNA viruses, no RNA stage › Herpesvirales › Herpesviridae › Gammaherpesvirinae › Lymphocryptovirus

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	404 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an essential role in the viral lytic DNA replication by acting as the polymerase accessory subunit. Stimulates the viral DNA polymerase activity and appears to function with it as a holoenzyme. Increases the processivity of the viral polymerase, probably by acting as a sliding clamp that prevents dissociation of the polymerase from the active template. In addition, BMRF1 transcriptionally activates the early BHLF1 promoter. Ref.4 Ref.9
Subunit structure	Homo-oligomerizes and adopts an oligomeric ring-shaped structure composed of 6 subunits. Forms a complex with the DNA-binding protein BALF2, the DNA polymerase subunit BALF5, and the alkaline exonuclease BGLF5. Interacts with BZLF1; this interaction may inhibit BZLF1-induced transcription of the BMRF1 promoter. Ref.4 Ref.5 Ref.6
Subcellular location	Virion tegument. Host nucleus. Note: BMRF1 shows homogenous, not dot-like, distribution in the replication compartments, which coincides with the newly synthesized viral DNA. Ref.7 Ref.8
Post-translational modification	Phosphorylated by the viral BGLF4 kinase. Ref.10
Sequence similarities	Belongs to the herpesviridae DNA polymerase accessory subunit family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Host nucleus Virion Virion tegument
Developmental stage	Early protein
Ligand	DNA-binding
Molecular function	Activator
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell viral tegument Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 404

404

DNA polymerase processivity factor BMRF1

PRO_0000116071

Amino acid modifications

Modified residue

337

1

Phosphoserine

Modified residue

344

1

Phosphothreonine

Modified residue

349

1

Phosphoserine

Modified residue

355

1

Phosphothreonine

Disulfide bond

95

Interchain

Disulfide bond

206

Interchain

Experimental info

Mutagenesis

314

1

S → A: No effect on phosphorylation. Ref.10

Mutagenesis

333

1

S → A: No effect on phosphorylation. Ref.10

Mutagenesis

337

1

S → A: Complete loss of phosphorylation; when associated with V-344; A-349 and V-355. Ref.10

Mutagenesis

344

1

T → V: Complete loss of phosphorylation; when associated with A-337; A-349 and V-355. Ref.10

Mutagenesis

349

1

S → A: Complete loss of phosphorylation; when associated with A-337; V-344 and V-355. Ref.10

Mutagenesis

355

1

T → V: Complete loss of phosphorylation; when associated with A-337; V-344 and A-349. Ref.10

Secondary structure

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404

Helix Strand Turn

Details...

Beta strand

2 – 9

8

Helix

13 – 17

5

Helix

18 – 28

11

Beta strand

31 – 37

7

Helix

38 – 42

5

Beta strand

46 – 52

7

Beta strand

54 – 63

10

Helix

65 – 67

3

Beta strand

68 – 73

6

Turn

77 – 79

3

Beta strand

82 – 89

8

Beta strand

94 – 96

3

Helix

97 – 101

5

Beta strand

106 – 115

10

Beta strand

117 – 119

3

Beta strand

125 – 132

8

Beta strand

138 – 144

7

Turn

152 – 156

5

Beta strand

161 – 166

6

Helix

169 – 181

13

Turn

182 – 184

3

Beta strand

185 – 192

8

Turn

193 – 196

4

Beta strand

197 – 202

6

Beta strand

205 – 210

6

Helix

218 – 220

3

Beta strand

226 – 228

3

Beta strand

232 – 235

4

Beta strand

239 – 244

6

Helix

245 – 255

11

Turn

258 – 260

3

Beta strand

261 – 268

8

Turn

269 – 271

3

Beta strand

272 – 283

12

Beta strand

288 – 294

7

Sequences

	Sequence		Length	Mass (Da)
	P03191 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 533B5D5ECC05F960	FASTA	404	43,374
	10 20 30 40 50 60 METTQTLRFK TKALAVLSKC YDHAQTHLKG GVLQVNLLSV NYGGPRLAAV ANAGTAGLIS 70 80 90 100 110 120 FEVSPDAVAE WQNHQSPEEA PAAVSFRNLA YGRTCVLGKE LFGSAVEQAS LQFYKRPQGG 130 140 150 160 170 180 SRPEFVKLTM EYDDKVSKSH HTCALMPYMP PASDRLRNEQ MIGQVLLMPK TASSLQKWAR 190 200 210 220 230 240 QQGSGGVKVT LNPDLYVTTY TSGEACLTLD YKPLSVGPYE AFTGPVAKAQ DVGAVEAHVV 250 260 270 280 290 300 CSVAADSLAA ALSLCRIPAV SVPILRFYRS GIIAVVAGLL TSAGDLPLDL SVILFNHASE 310 320 330 340 350 360 EAAASTASEP EDKSPRVQPL GTGLQQRPRH TVSPSPSPPP PPRTPTWESP ARPETPSPAI 370 380 390 400 PSHSSNTALE RPLAVQLARK RTSSEARQKQ KHPKKVKQAF NPLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA sequence and expression of the B95-8 Epstein-Barr virus genome." Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J., Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C., Tuffnell P.S., Barrell B.G. Nature 310:207-211(1984) [PubMed: 6087149] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Characterization of a cDNA clone corresponding to a transcript from the Epstein-Barr virus BamHI M fragment: evidence for overlapping mRNAs." Pfitzner A.J., Strominger J.L., Speck S.H. J. Virol. 61:2943-2946(1987) [PubMed: 2441081] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 123-404.
[3]	"A second Epstein-Barr virus early antigen gene in BamHI fragment M encodes a 48- to 50-kilodalton nuclear protein." Cho M.-S., Milman G., Hayward S.D. J. Virol. 56:860-866(1985) [PubMed: 2999442] [Abstract] Cited for: CHARACTERIZATION.
[4]	"Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication." Zhang Q., Hong Y., Dorsky D., Holley-Guthrie E., Zalani S., Elshiekh N.A., Kiehl A., Le T., Kenney S. J. Virol. 70:5131-5142(1996) [PubMed: 8764021] [Abstract] Cited for: FUNCTION, INTERACTION WITH BZLF1.
[5]	"A major DNA binding protein encoded by BALF2 open reading frame of Epstein-Barr virus (EBV) forms a complex with other EBV DNA-binding proteins: DNAase, EA-D, and DNA polymerase." Zeng Y., Middeldorp J., Madjar J.J., Ooka T. Virology 239:285-295(1997) [PubMed: 9434720] [Abstract] Cited for: INTERACTION WITH BALF2; BALF5 AND BGLF5.
[6]	"The Epstein-Barr virus polymerase accessory factor BMRF1 adopts a ring-shaped structure as visualized by electron microscopy." Makhov A.M., Subramanian D., Holley-Guthrie E., Kenney S.C., Griffith J.D. J. Biol. Chem. 279:40358-40361(2004) [PubMed: 15286084] [Abstract] Cited for: OLIGOMERIZATION.
[7]	"Proteins of purified Epstein-Barr virus." Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E., Illanes D., Sarracino D., Kieff E. Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004) [PubMed: 15534216] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Architecture of replication compartments formed during Epstein-Barr virus lytic replication." Daikoku T., Kudoh A., Fujita M., Sugaya Y., Isomura H., Shirata N., Tsurumi T. J. Virol. 79:3409-3418(2005) [PubMed: 15731235] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"The Epstein-Barr virus BMRF1 gene is essential for lytic virus replication." Neuhierl B., Delecluse H.J. J. Virol. 80:5078-5081(2006) [PubMed: 16641300] [Abstract] Cited for: FUNCTION.
[10]	"Effect of phosphorylation on the transactivation activity of Epstein-Barr virus BMRF1, a major target of the viral BGLF4 kinase." Yang P.W., Chang S.S., Tsai C.H., Chao Y.H., Chen M.R. J. Gen. Virol. 89:884-895(2008) [PubMed: 18343828] [Abstract] Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-314; SER-333; SER-337; THR-344; SER-349 AND THR-355.
[11]	"Crystal structure of EBV-DNA polymerase accessory protein BMRF1." RIKEN structural genomics initiative (RSGI) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-314.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V01555 Genomic DNA. Translation: CAA24844.1.
M17322 Genomic DNA. Translation: AAA45877.1.
AJ507799 Genomic DNA. Translation: CAD53407.1.

PIR

QQBE13. B43041.

RefSeq

YP_401657.1. NC_007605.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Z0L	X-ray	2.90	A/B/C/D/E/F/G/H	1-314	[»]

ProteinModelPortal

P03191.

SMR

P03191. Positions 1-299.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

3783718.

Phylogenomic databases

ProtClustDB

CLSP2509696.

Family and domain databases

InterPro

IPR007013. DNA_replication_acc_fac_herpes.
[Graphical view]

Pfam

PF04929. Herpes_DNAp_acc. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

EAD_EBVB9

Accession

Primary (citable) accession number: P03191
Secondary accession number(s): Q777F9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	September 21, 2011
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program