BZLF1_EBVB9
ID BZLF1_EBVB9 Reviewed; 245 AA.
AC P03206; Q69127; Q777E5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 25-MAY-2022, entry version 144.
DE RecName: Full=Trans-activator protein BZLF1;
DE Short=EB1;
DE AltName: Full=Zebra;
GN ORFNames=BZLF1;
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 RNA], AND CHARACTERIZATION.
RX PubMed=3041034; DOI=10.1128/jvi.61.10.3120-3132.1987;
RA Biggin M., Bodescot M., Perricaudet M., Farrel P.;
RT "Epstein-Barr virus gene expression in P3HR1-superinfected Raji cells.";
RL J. Virol. 61:3120-3132(1987).
RN [3]
RP DNA-BINDING.
RX PubMed=2540954; DOI=10.1002/j.1460-2075.1989.tb03356.x;
RA Farrel P.J., Rowe D.T., Rooney C.M., Kouzarides T.;
RT "Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus
RT AP-1 site and is related to c-fos.";
RL EMBO J. 8:127-132(1989).
RN [4]
RP STRUCTURE, AND FUNCTION.
RX PubMed=2157874; DOI=10.1128/jvi.64.5.2110-2116.1990;
RA Packham G., Economou A., Rooney C.M., Rowe D.T., Farrel P.J.;
RT "Structure and function of the Epstein-Barr virus BZLF1 protein.";
RL J. Virol. 64:2110-2116(1990).
RN [5]
RP FUNCTION.
RX PubMed=1847997;
RA Kouzarides T., Packham G., Cook A., Farrell P.J.;
RT "The BZLF1 protein of EBV has a coiled coil dimerisation domain without a
RT heptad leucine repeat but with homology to the C/EBP leucine zipper.";
RL Oncogene 6:195-204(1991).
RN [6]
RP FUNCTION.
RX PubMed=8404860; DOI=10.1002/j.1460-2075.1993.tb06070.x;
RA Schepers A., Pich D., Hammerschmidt W.;
RT "A transcription factor with homology to the AP-1 family links RNA
RT transcription and DNA replication in the lytic cycle of Epstein-Barr
RT virus.";
RL EMBO J. 12:3921-3929(1993).
RN [7]
RP INTERACTION WITH HUMAN RACK1, AND SUBCELLULAR LOCATION.
RX PubMed=10849009; DOI=10.1046/j.1432-1327.2000.01430.x;
RA Baumann M., Gires O., Kolch W., Mischak H., Zeidler R., Pich D.,
RA Hammerschmidt W.;
RT "The PKC targeting protein RACK1 interacts with the Epstein-Barr virus
RT activator protein BZLF1.";
RL Eur. J. Biochem. 267:3891-3901(2000).
RN [8]
RP INTERACTION WITH HUMAN UBN1.
RX PubMed=10725330; DOI=10.1083/jcb.148.6.1165;
RA Aho S., Buisson M., Pajunen T., Ryoo Y.W., Giot J.-F., Gruffat H.,
RA Sergeant A., Uitto J.;
RT "Ubinuclein, a novel nuclear protein interacting with cellular and viral
RT transcription factors.";
RL J. Cell Biol. 148:1165-1176(2000).
RN [9]
RP FUNCTION.
RX PubMed=17079287; DOI=10.1128/jvi.01416-06;
RA Wen W., Iwakiri D., Yamamoto K., Maruo S., Kanda T., Takada K.;
RT "Epstein-Barr virus BZLF1 gene, a switch from latency to lytic infection,
RT is expressed as an immediate-early gene after primary infection of B
RT lymphocytes.";
RL J. Virol. 81:1037-1042(2007).
RN [10]
RP INTERACTION WITH HUMAN CRTC2.
RX PubMed=19164291; DOI=10.1074/jbc.m808466200;
RA Murata T., Sato Y., Nakayama S., Kudoh A., Iwahori S., Isomura H.,
RA Tajima M., Hishiki T., Ohshima T., Hijikata M., Shimotohno K., Tsurumi T.;
RT "TORC2, a coactivator of cAMP-response element-binding protein, promotes
RT Epstein-Barr virus reactivation from latency through interaction with viral
RT BZLF1 protein.";
RL J. Biol. Chem. 284:8033-8041(2009).
RN [11]
RP FUNCTION.
RX PubMed=19144704; DOI=10.1128/jvi.02500-08;
RA McDonald C.M., Petosa C., Farrell P.J.;
RT "Interaction of Epstein-Barr virus BZLF1 C-terminal tail structure and core
RT zipper is required for DNA replication but not for promoter
RT transactivation.";
RL J. Virol. 83:3397-3401(2009).
RN [12]
RP FUNCTION, AND INTERACTION WITH HUMAN PAX5.
RX PubMed=23678172; DOI=10.1128/jvi.00546-13;
RA Raver R.M., Panfil A.R., Hagemeier S.R., Kenney S.C.;
RT "The B-cell-specific transcription factor and master regulator Pax5
RT promotes Epstein-Barr virus latency by negatively regulating the viral
RT immediate early protein BZLF1.";
RL J. Virol. 87:8053-8063(2013).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 175-236.
RX PubMed=16483937; DOI=10.1016/j.molcel.2006.01.006;
RA Petosa C., Morand P., Baudin F., Moulin M., Artero J.B., Muller C.W.;
RT "Structural basis of lytic cycle activation by the Epstein-Barr virus ZEBRA
RT protein.";
RL Mol. Cell 21:565-572(2006).
RN [14] {ECO:0007744|PDB:5SZX}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 175-236, SUBUNIT, DNA-BINDING,
RP AND MUTAGENESIS OF SER-186.
RX PubMed=28158710; DOI=10.1093/nar/gkx057;
RA Hong S., Wang D., Horton J.R., Zhang X., Speck S.H., Blumenthal R.M.,
RA Cheng X.;
RT "Methyl-dependent and spatial-specific DNA recognition by the orthologous
RT transcription factors human AP-1 and Epstein-Barr virus Zta.";
RL Nucleic Acids Res. 45:2503-2515(2017).
CC -!- FUNCTION: Plays a key role in the switch from latent infection to lytic
CC cycle producing new virions. Acts as a transcription factor, inducing
CC early lytic cycle genes, and as a origin binding protein for genome
CC replication. BZLF1 activates the promoter of another EBV gene
CC (BSLF2+BMLF1). {ECO:0000269|PubMed:17079287,
CC ECO:0000269|PubMed:1847997, ECO:0000269|PubMed:19144704,
CC ECO:0000269|PubMed:2157874, ECO:0000269|PubMed:23678172,
CC ECO:0000269|PubMed:8404860}.
CC -!- SUBUNIT: Homodimer (PubMed:28158710). Interacts with human UBN1, CRTC2
CC and RACK1. Interacts (via N-terminus) with human PAX5 (via N-terminus);
CC this interaction inhibits BZLF1-mediated lytic viral reactivation
CC (PubMed:23678172). {ECO:0000269|PubMed:10725330,
CC ECO:0000269|PubMed:10849009, ECO:0000269|PubMed:19164291,
CC ECO:0000269|PubMed:23678172, ECO:0000269|PubMed:28158710}.
CC -!- INTERACTION:
CC P03206; Q53ET0: CRTC2; Xeno; NbExp=3; IntAct=EBI-2621186, EBI-1181987;
CC P03206; P63244: RACK1; Xeno; NbExp=5; IntAct=EBI-2621186, EBI-296739;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:10849009}.
CC -!- SIMILARITY: Belongs to the bZIP 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; CAA24861.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53423.1; -; Genomic_DNA.
DR EMBL; M17547; AAA66529.1; -; mRNA.
DR RefSeq; YP_401673.1; NC_007605.1.
DR PDB; 1ZSD; X-ray; 1.70 A; C=54-64.
DR PDB; 2AK4; X-ray; 2.50 A; C/H/M/S=52-64.
DR PDB; 2AXF; X-ray; 1.80 A; C=77-86.
DR PDB; 2AXG; X-ray; 2.00 A; C=77-86.
DR PDB; 2C9L; X-ray; 2.25 A; Y/Z=175-236.
DR PDB; 2C9N; X-ray; 3.30 A; Y/Z=175-236.
DR PDB; 2NX5; X-ray; 2.70 A; C/H/M/S=54-64.
DR PDB; 3KWW; X-ray; 2.18 A; C=52-64.
DR PDB; 3KXF; X-ray; 3.10 A; Q/R/S/T=52-64.
DR PDB; 3SPV; X-ray; 1.30 A; C=190-197.
DR PDB; 3VFN; X-ray; 1.50 A; C=52-64.
DR PDB; 3VFO; X-ray; 1.70 A; C=52-64.
DR PDB; 3VFP; X-ray; 1.85 A; C=52-64.
DR PDB; 3VFR; X-ray; 1.85 A; C=52-64.
DR PDB; 5SZX; X-ray; 2.25 A; A/B=175-236.
DR PDB; 7NX5; X-ray; 2.50 A; A/B/E/F=175-236.
DR PDBsum; 1ZSD; -.
DR PDBsum; 2AK4; -.
DR PDBsum; 2AXF; -.
DR PDBsum; 2AXG; -.
DR PDBsum; 2C9L; -.
DR PDBsum; 2C9N; -.
DR PDBsum; 2NX5; -.
DR PDBsum; 3KWW; -.
DR PDBsum; 3KXF; -.
DR PDBsum; 3SPV; -.
DR PDBsum; 3VFN; -.
DR PDBsum; 3VFO; -.
DR PDBsum; 3VFP; -.
DR PDBsum; 3VFR; -.
DR PDBsum; 5SZX; -.
DR PDBsum; 7NX5; -.
DR SMR; P03206; -.
DR BioGRID; 971786; 3.
DR IntAct; P03206; 10.
DR MINT; P03206; -.
DR BindingDB; P03206; -.
DR ChEMBL; CHEMBL1293280; -.
DR iPTMnet; P03206; -.
DR PRIDE; P03206; -.
DR DNASU; 3783744; -.
DR GeneID; 3783744; -.
DR KEGG; vg:3783744; -.
DR SIGNOR; P03206; -.
DR EvolutionaryTrace; P03206; -.
DR PRO; PR:P03206; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0039646; P:modulation by virus of host G0/G1 transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:CACAO.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0019046; P:release from viral latency; IEA:UniProtKB-KW.
DR GO; GO:0039557; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity; IEA:UniProtKB-KW.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR017339; Trans-activator_BZLF1_HHV-4.
DR PIRSF; PIRSF037966; BZLF1; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Early protein;
KW G0/G1 host cell cycle checkpoint dysregulation by virus; Host nucleus;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host IRF7 by virus; Inhibition of host RLR pathway by virus;
KW Modulation of host cell cycle by virus; Reference proteome; Transcription;
KW Transcription regulation; Viral immunoevasion; Viral latency;
KW Viral reactivation from latency.
FT CHAIN 1..245
FT /note="Trans-activator protein BZLF1"
FT /id="PRO_0000076541"
FT DOMAIN 170..228
FT /note="bZIP"
FT REGION 178..195
FT /note="Basic motif"
FT /evidence="ECO:0000250"
FT REGION 196..228
FT /note="Leucine-zipper"
FT /evidence="ECO:0000250"
FT MUTAGEN 186
FT /note="S->A: Loss of binding to BRLF1 promoter."
FT /evidence="ECO:0000269|PubMed:28158710"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2AK4"
FT HELIX 175..221
FT /evidence="ECO:0007829|PDB:2C9L"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:2C9L"
SQ SEQUENCE 245 AA; 26860 MW; 7F3D55D79F1F0196 CRC64;
MMDPNSTSED VKFTPDPYQV PFVQAFDQAT RVYQDLGGPS QAPLPCVLWP VLPEPLPQGQ
LTAYHVSTAP TGSWFSAPQP APENAYQAYA APQLFPVSDI TQNQQTNQAG GEAPQPGDNS
TVQTAAAVVF ACPGANQGQQ LADIGVPQPA PVAAPARRTR KPQQPESLEE CDSELEIKRY
KNRVASRKCR AKFKQLLQHY REVAAAKSSE NDRLRLLLKQ MCPSLDVDSI IPRTPDVLHE
DLLNF
