EAD_EBVB9
ID EAD_EBVB9 Reviewed; 404 AA.
AC P03191; Q777F9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=DNA polymerase processivity factor BMRF1;
DE AltName: Full=Early antigen protein D;
DE Short=EA-D;
DE AltName: Full=Polymerase accessory subunit;
GN ORFNames=BMRF1;
OS Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
OX NCBI_TaxID=10377;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=6087149; DOI=10.1038/310207a0;
RA Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J.,
RA Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C.,
RA Tuffnell P.S., Barrell B.G.;
RT "DNA sequence and expression of the B95-8 Epstein-Barr virus genome.";
RL Nature 310:207-211(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 123-404.
RX PubMed=2441081; DOI=10.1128/jvi.61.9.2943-2946.1987;
RA Pfitzner A.J., Strominger J.L., Speck S.H.;
RT "Characterization of a cDNA clone corresponding to a transcript from the
RT Epstein-Barr virus BamHI M fragment: evidence for overlapping mRNAs.";
RL J. Virol. 61:2943-2946(1987).
RN [3]
RP CHARACTERIZATION.
RX PubMed=2999442; DOI=10.1128/jvi.56.3.860-866.1985;
RA Cho M.-S., Milman G., Hayward S.D.;
RT "A second Epstein-Barr virus early antigen gene in BamHI fragment M encodes
RT a 48- to 50-kilodalton nuclear protein.";
RL J. Virol. 56:860-866(1985).
RN [4]
RP FUNCTION, AND INTERACTION WITH BZLF1.
RX PubMed=8764021; DOI=10.1128/jvi.70.8.5131-5142.1996;
RA Zhang Q., Hong Y., Dorsky D., Holley-Guthrie E., Zalani S., Elshiekh N.A.,
RA Kiehl A., Le T., Kenney S.;
RT "Functional and physical interactions between the Epstein-Barr virus (EBV)
RT proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic
RT replication.";
RL J. Virol. 70:5131-5142(1996).
RN [5]
RP INTERACTION WITH BALF2; BALF5 AND BGLF5.
RX PubMed=9434720; DOI=10.1006/viro.1997.8891;
RA Zeng Y., Middeldorp J., Madjar J.J., Ooka T.;
RT "A major DNA binding protein encoded by BALF2 open reading frame of
RT Epstein-Barr virus (EBV) forms a complex with other EBV DNA-binding
RT proteins: DNAase, EA-D, and DNA polymerase.";
RL Virology 239:285-295(1997).
RN [6]
RP OLIGOMERIZATION.
RX PubMed=15286084; DOI=10.1074/jbc.m408733200;
RA Makhov A.M., Subramanian D., Holley-Guthrie E., Kenney S.C., Griffith J.D.;
RT "The Epstein-Barr virus polymerase accessory factor BMRF1 adopts a ring-
RT shaped structure as visualized by electron microscopy.";
RL J. Biol. Chem. 279:40358-40361(2004).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=15534216; DOI=10.1073/pnas.0407320101;
RA Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E.,
RA Illanes D., Sarracino D., Kieff E.;
RT "Proteins of purified Epstein-Barr virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=15731235; DOI=10.1128/jvi.79.6.3409-3418.2005;
RA Daikoku T., Kudoh A., Fujita M., Sugaya Y., Isomura H., Shirata N.,
RA Tsurumi T.;
RT "Architecture of replication compartments formed during Epstein-Barr virus
RT lytic replication.";
RL J. Virol. 79:3409-3418(2005).
RN [9]
RP FUNCTION.
RX PubMed=16641300; DOI=10.1128/jvi.80.10.5078-5081.2006;
RA Neuhierl B., Delecluse H.J.;
RT "The Epstein-Barr virus BMRF1 gene is essential for lytic virus
RT replication.";
RL J. Virol. 80:5078-5081(2006).
RN [10]
RP PHOSPHORYLATION AT SER-337; THR-344; SER-349 AND THR-355, AND MUTAGENESIS
RP OF SER-314; SER-333; SER-337; THR-344; SER-349 AND THR-355.
RX PubMed=18343828; DOI=10.1099/vir.0.83546-0;
RA Yang P.W., Chang S.S., Tsai C.H., Chao Y.H., Chen M.R.;
RT "Effect of phosphorylation on the transactivation activity of Epstein-Barr
RT virus BMRF1, a major target of the viral BGLF4 kinase.";
RL J. Gen. Virol. 89:884-895(2008).
RN [11] {ECO:0007744|PDB:2Z0L}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-314, FUNCTION, SUBUNIT, AND
RP DISULFIDE BONDS.
RX PubMed=19801550; DOI=10.1074/jbc.m109.051581;
RA Murayama K., Nakayama S., Kato-Murayama M., Akasaka R., Ohbayashi N.,
RA Kamewari-Hayami Y., Terada T., Shirouzu M., Tsurumi T., Yokoyama S.;
RT "Crystal structure of epstein-barr virus DNA polymerase processivity factor
RT BMRF1.";
RL J. Biol. Chem. 284:35896-35905(2009).
CC -!- FUNCTION: Plays an essential role in the viral lytic DNA replication by
CC acting as the polymerase accessory subunit. Stimulates the viral DNA
CC polymerase activity and appears to function with it as a holoenzyme.
CC Increases the processivity of the viral polymerase, probably by acting
CC as a sliding clamp that prevents dissociation of the polymerase from
CC the active template. In addition, BMRF1 transcriptionally activates the
CC early BHLF1 promoter. {ECO:0000269|PubMed:16641300,
CC ECO:0000269|PubMed:19801550, ECO:0000269|PubMed:8764021}.
CC -!- SUBUNIT: Homodimer (PubMed:19801550). Homooligomerizes and adopts an
CC oligomeric ring-shaped structure composed of 6 subunits. Forms a
CC complex with the DNA-binding protein BALF2, the DNA polymerase subunit
CC BALF5, and the alkaline exonuclease BGLF5. Interacts with BZLF1; this
CC interaction may inhibit BZLF1-induced transcription of the BMRF1
CC promoter. {ECO:0000269|PubMed:19801550, ECO:0000269|PubMed:8764021,
CC ECO:0000269|PubMed:9434720}.
CC -!- SUBCELLULAR LOCATION: Virion tegument. Host nucleus. Note=BMRF1 shows
CC homogeneous, not dot-like, distribution in the replication
CC compartments, which coincides with the newly synthesized viral DNA.
CC -!- PTM: Phosphorylated by the viral BGLF4 kinase.
CC {ECO:0000269|PubMed:18343828}.
CC -!- SIMILARITY: Belongs to the herpesviridae DNA polymerase accessory
CC subunit family. {ECO:0000305}.
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DR EMBL; V01555; CAA24844.1; -; Genomic_DNA.
DR EMBL; M17322; AAA45877.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53407.1; -; Genomic_DNA.
DR PIR; B43041; QQBE13.
DR RefSeq; YP_401657.1; NC_007605.1.
DR PDB; 2Z0L; X-ray; 2.90 A; A/B/C/D/E/F/G/H=1-314.
DR PDBsum; 2Z0L; -.
DR SMR; P03191; -.
DR BioGRID; 971760; 1.
DR iPTMnet; P03191; -.
DR PRIDE; P03191; -.
DR DNASU; 3783718; -.
DR GeneID; 3783718; -.
DR KEGG; vg:3783718; -.
DR EvolutionaryTrace; P03191; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0039686; P:bidirectional double-stranded viral DNA replication; IDA:UniProtKB.
DR InterPro; IPR007013; DNA_pol_proc_fac_herpes.
DR Pfam; PF04929; Herpes_DNAp_acc; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Disulfide bond; DNA-binding; Early protein;
KW Host nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Virion; Virion tegument.
FT CHAIN 1..404
FT /note="DNA polymerase processivity factor BMRF1"
FT /id="PRO_0000116071"
FT REGION 302..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..357
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18343828"
FT MOD_RES 344
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18343828"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18343828"
FT MOD_RES 355
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18343828"
FT DISULFID 95
FT /note="Interchain"
FT /evidence="ECO:0007744|PDB:2Z0L"
FT DISULFID 206
FT /note="Interchain"
FT /evidence="ECO:0007744|PDB:2Z0L"
FT MUTAGEN 314
FT /note="S->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:18343828"
FT MUTAGEN 333
FT /note="S->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:18343828"
FT MUTAGEN 337
FT /note="S->A: Complete loss of phosphorylation; when
FT associated with V-344; A-349 and V-355."
FT /evidence="ECO:0000269|PubMed:18343828"
FT MUTAGEN 344
FT /note="T->V: Complete loss of phosphorylation; when
FT associated with A-337; A-349 and V-355."
FT /evidence="ECO:0000269|PubMed:18343828"
FT MUTAGEN 349
FT /note="S->A: Complete loss of phosphorylation; when
FT associated with A-337; V-344 and V-355."
FT /evidence="ECO:0000269|PubMed:18343828"
FT MUTAGEN 355
FT /note="T->V: Complete loss of phosphorylation; when
FT associated with A-337; V-344 and A-349."
FT /evidence="ECO:0000269|PubMed:18343828"
FT STRAND 2..9
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 13..17
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 38..42
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 54..63
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:2Z0L"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 97..101
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 106..115
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 125..132
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 138..144
FT /evidence="ECO:0007829|PDB:2Z0L"
FT TURN 152..156
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 161..166
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 169..181
FT /evidence="ECO:0007829|PDB:2Z0L"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 185..192
FT /evidence="ECO:0007829|PDB:2Z0L"
FT TURN 193..196
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 197..202
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:2Z0L"
FT HELIX 245..255
FT /evidence="ECO:0007829|PDB:2Z0L"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 261..268
FT /evidence="ECO:0007829|PDB:2Z0L"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 272..283
FT /evidence="ECO:0007829|PDB:2Z0L"
FT STRAND 288..294
FT /evidence="ECO:0007829|PDB:2Z0L"
SQ SEQUENCE 404 AA; 43374 MW; 533B5D5ECC05F960 CRC64;
METTQTLRFK TKALAVLSKC YDHAQTHLKG GVLQVNLLSV NYGGPRLAAV ANAGTAGLIS
FEVSPDAVAE WQNHQSPEEA PAAVSFRNLA YGRTCVLGKE LFGSAVEQAS LQFYKRPQGG
SRPEFVKLTM EYDDKVSKSH HTCALMPYMP PASDRLRNEQ MIGQVLLMPK TASSLQKWAR
QQGSGGVKVT LNPDLYVTTY TSGEACLTLD YKPLSVGPYE AFTGPVAKAQ DVGAVEAHVV
CSVAADSLAA ALSLCRIPAV SVPILRFYRS GIIAVVAGLL TSAGDLPLDL SVILFNHASE
EAAASTASEP EDKSPRVQPL GTGLQQRPRH TVSPSPSPPP PPRTPTWESP ARPETPSPAI
PSHSSNTALE RPLAVQLARK RTSSEARQKQ KHPKKVKQAF NPLI
