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 02-SEP-2026, entry version 108. DE RecName: Full=DNA polymerase processivity factor BMRF1; DE AltName: Full=Early Antigen Diffused; 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; Orthoherpesviridae; Gammaherpesvirinae; Lymphocryptovirus; OC Lymphocryptovirus humangamma4; Epstein-Barr virus. 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 GENOME REANNOTATION. RX PubMed=12771413; DOI=10.1099/vir.0.19054-0; RA de Jesus O., Smith P.R., Spender L.C., Elgueta Karstegl C., Niller H.H., RA Huang D., Farrell P.J.; RT "Updated Epstein-Barr virus (EBV) DNA sequence and analysis of a promoter RT for the BART (CST, BARF0) RNAs of EBV."; RL Virology 84:1443-1450(2003). RN [4] 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 [5] RP INTERACTION WITH BZLF1, AND FUNCTION. 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 [6] 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 [7] RP FUNCTION. RX PubMed=9126259; DOI=10.1006/viro.1997.8470; RA Zhang Q., Holley-Guthrie E., Ge J.Q., Dorsky D., Kenney S.; RT "The Epstein-Barr virus (EBV) DNA polymerase accessory protein, BMRF1, RT activates the essential downstream component of the EBV oriLyt."; RL Virology 230:22-34(1997). RN [8] RP DOMAIN. RX PubMed=9934686; DOI=10.1099/0022-1317-80-1-69; RA Zhang Q., Holley-Guthrie E., Dorsky D., Kenney S.; RT "Identification of transactivator and nuclear localization domains in the RT Epstein-Barr virus DNA polymerase accessory protein, BMRF1."; RL J. Gen. Virol. 80:69-74(1999). RN [9] RP SUBUNIT. 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] RP FUNCTION. RX PubMed=24501404; DOI=10.1128/jvi.00059-14; RA Paladino P., Marcon E., Greenblatt J., Frappier L.; RT "Identification of herpesvirus proteins that contribute to G1/S arrest."; RL J. Virol. 88:4480-4492(2014). RN [15] RP FUNCTION, INTERACTION WITH HOST NURD COMPLEX, AND MUTAGENESIS OF ARG-256; RP 387-ARG--LYS-389 AND PRO-393. RX PubMed=31462557; DOI=10.1128/jvi.01070-19; RA Salamun S.G., Sitz J., De La Cruz-Herrera C.F., Yockteng-Melgar J., RA Marcon E., Greenblatt J., Fradet-Turcotte A., Frappier L.; RT "The Epstein-Barr Virus BMRF1 Protein Activates Transcription and Inhibits RT the DNA Damage Response by Binding NuRD."; RL J. Virol. 93:0-0(2019). RN [16] {ECO:0007744|PDB:2Z0L} RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 1-314, FUNCTION, SUBUNIT, RP DISULFIDE BONDS, AND DOMAIN. 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: Acts as a DNA polymerase processivity factor; a CC transcriptional activator for several EBV promoters and inhibits the CC host DNA damage response (DDR) to double-stranded DNA breaks CC (PubMed:16641300, PubMed:19801550, PubMed:31462557, PubMed:8764021). CC Plays an essential role in the viral lytic DNA replication by acting as CC a polymerase accessory subunit (PubMed:16641300, PubMed:19801550). CC Stimulates the viral DNA polymerase activity and appears to function CC with it as a holoenzyme (PubMed:19801550). Increases the processivity CC of the viral polymerase, probably by acting as a sliding clamp that CC prevents dissociation of the polymerase from the active template CC (PubMed:19801550). In addition, BMRF1 transcriptionally activates the CC oriLyt early BHLF1 promoter (PubMed:8764021, PubMed:9126259). Promotes CC G1/S cell cycle arrest through p53 induction (PubMed:24501404). CC {ECO:0000269|PubMed:16641300, ECO:0000269|PubMed:19801550, CC ECO:0000269|PubMed:24501404, ECO:0000269|PubMed:31462557, CC ECO:0000269|PubMed:8764021, ECO:0000269|PubMed:9126259}. CC -!- SUBUNIT: Homodimer (PubMed:19801550). Two dimers can adopt a tetrameric CC ring-like structure (PubMed:15286084, PubMed:19801550). Forms a complex CC with the DNA-binding protein BALF2, the DNA polymerase subunit BALF5, CC and the alkaline exonuclease BGLF5 (PubMed:9434720). Interacts (via N- CC terminus) with BZLF1 (via bZIP domain); this interaction may inhibit CC BZLF1-induced transcription of the BMRF1 promoter (PubMed:8764021). CC Interacts (via C-terminus) with host NuRD complex; this interaction is CC important for transcriptional activation of EBV promoters and CC inhibition of the ubiquitination step of DDR signaling CC (PubMed:31462557). {ECO:0000269|PubMed:15286084, CC ECO:0000269|PubMed:19801550, ECO:0000269|PubMed:31462557, CC ECO:0000269|PubMed:8764021, 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 -!- DOMAIN: The N-terminus is important for dimerization, DNA binding, and CC DNA polymerase processivity (PubMed:19801550). The C-terminus mediates CC transcriptional activation (PubMed:9934686). CC {ECO:0000269|PubMed:19801550, ECO:0000269|PubMed:9934686}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 AlphaFoldDB; P03191; -. DR SMR; P03191; -. DR BioGRID; 971760; 1. DR iPTMnet; P03191; -. DR DNASU; 3783718; -. DR GeneID; 3783718; -. DR KEGG; vg:3783718; -. DR EvolutionaryTrace; P03191; -. DR PRO; PR:P03191; -. DR Proteomes; UP000153037; Segment. 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 GO; GO:0039645; P:symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint; IEA:UniProtKB-KW. DR Gene3D; 3.70.10.10; -; 1. DR InterPro; IPR007013; DNA_pol_proc_fac_herpes. DR Pfam; PF04929; Herpes_DNAp_acc; 1. DR PDBsum; 2Z0L; -. PE 1: Evidence at protein level; KW 3D-structure; Activator; Disulfide bond; DNA-binding; Early protein; KW G1/S host cell cycle checkpoint dysregulation by virus; Host nucleus; KW Host-virus interaction; Modulation of host cell cycle by virus; KW 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 1..300 FT /note="Homodimerization; DNA binding and DNA polymerase FT processivity" FT /evidence="ECO:0000269|PubMed:19801550" FT REGION 301..404 FT /note="Transcriptional activation" FT /evidence="ECO:0000269|PubMed:9934686" FT REGION 302..404 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 335..344 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 256 FT /note="R->E: Complete loss of DNA binding activity and FT transactivation of the BDLF3 and BLLF1 promoters." FT /evidence="ECO:0000269|PubMed:31462557" 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 MUTAGEN 387..389 FT /note="RQK->AQA: Complete loss of binding to host NuRD. FT Complete loss of transcriptional activity of on BDLF3 and FT BLLF1 EBV promoters." FT /evidence="ECO:0000269|PubMed:31462557" FT MUTAGEN 393 FT /note="P->A: Complete loss of binding to host NuRD. FT Complete loss of transcriptional activity of on BDLF3 and FT BLLF1 EBV promoters." FT /evidence="ECO:0000269|PubMed:31462557" 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 //