KR2_EBVB9
ID KR2_EBVB9 Reviewed; 429 AA.
AC P13288; Q777D1;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Serine/threonine-protein kinase BGLF4;
DE EC=2.7.11.1 {ECO:0000269|PubMed:31291580};
GN ORFNames=BGLF4;
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 CHARACTERIZATION.
RX PubMed=2535748; DOI=10.1128/jvi.63.1.450-455.1989;
RA Smith R.F., Smith T.F.;
RT "Identification of new protein kinase-related genes in three herpesviruses,
RT herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus.";
RL J. Virol. 63:450-455(1989).
RN [3]
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 [4]
RP SUBCELLULAR LOCATION.
RX PubMed=16298966; DOI=10.1099/vir.0.81313-0;
RA Wang J.T., Yang P.W., Lee C.P., Han C.H., Tsai C.H., Chen M.R.;
RT "Detection of Epstein-Barr virus BGLF4 protein kinase in virus replication
RT compartments and virus particles.";
RL J. Gen. Virol. 86:3215-3225(2005).
RN [5]
RP FUNCTION.
RX PubMed=16698993; DOI=10.1128/jvi.02674-05;
RA Asai R., Kato A., Kato K., Kanamori-Koyama M., Sugimoto K., Sairenji T.,
RA Nishiyama Y., Kawaguchi Y.;
RT "Epstein-Barr virus protein kinase BGLF4 is a virion tegument protein that
RT dissociates from virions in a phosphorylation-dependent process and
RT phosphorylates the viral immediate-early protein BZLF1.";
RL J. Virol. 80:5125-5134(2006).
RN [6]
RP FUNCTION.
RX PubMed=17360754; DOI=10.1128/jvi.00120-07;
RA Lee C.P., Chen J.Y., Wang J.T., Kimura K., Takemoto A., Lu C.C., Chen M.R.;
RT "Epstein-Barr virus BGLF4 kinase induces premature chromosome condensation
RT through activation of condensin and topoisomerase II.";
RL J. Virol. 81:5166-5180(2007).
RN [7]
RP FUNCTION.
RX PubMed=17360761; DOI=10.1128/jvi.02398-06;
RA Gershburg E., Raffa S., Torrisi M.R., Pagano J.S.;
RT "Epstein-Barr virus-encoded protein kinase (BGLF4) is involved in
RT production of infectious virus.";
RL J. Virol. 81:5407-5412(2007).
RN [8]
RP FUNCTION.
RX PubMed=18815303; DOI=10.1128/jvi.01100-08;
RA Lee C.P., Huang Y.H., Lin S.F., Chang Y., Chang Y.H., Takada K., Chen M.R.;
RT "Epstein-Barr virus BGLF4 kinase induces disassembly of the nuclear lamina
RT to facilitate virion production.";
RL J. Virol. 82:11913-11926(2008).
RN [9]
RP FUNCTION.
RX PubMed=19244323; DOI=10.1128/jvi.02378-08;
RA Zhu J., Liao G., Shan L., Zhang J., Chen M.R., Hayward G.S., Hayward S.D.,
RA Desai P., Zhu H.;
RT "Protein array identification of substrates of the epstein-barr virus
RT protein kinase BGLF4.";
RL J. Virol. 83:5219-5231(2009).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST NUP62 AND NUP153.
RX PubMed=22623767; DOI=10.1128/jvi.01058-12;
RA Chang C.W., Lee C.P., Huang Y.H., Yang P.W., Wang J.T., Chen M.R.;
RT "Epstein-Barr virus protein kinase BGLF4 targets the nucleus through
RT interaction with nucleoporins.";
RL J. Virol. 86:8072-8085(2012).
RN [11]
RP FUNCTION, INTERACTION WITH HOST SUMO1 AND SUMO2, REGION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22398289; DOI=10.1128/jvi.00314-12;
RA Li R., Wang L., Liao G., Guzzo C.M., Matunis M.J., Zhu H., Hayward S.D.;
RT "SUMO binding by the Epstein-Barr virus protein kinase BGLF4 is crucial for
RT BGLF4 function.";
RL J. Virol. 86:5412-5421(2012).
RN [12]
RP FUNCTION.
RX PubMed=25410863; DOI=10.1128/jvi.02880-14;
RA Chang C.W., Lee C.P., Su M.T., Tsai C.H., Chen M.R.;
RT "BGLF4 kinase modulates the structure and transport preference of the
RT nuclear pore complex to facilitate nuclear import of Epstein-Barr virus
RT lytic proteins.";
RL J. Virol. 89:1703-1718(2015).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31291580; DOI=10.1016/j.celrep.2019.04.020;
RA Zhang K., Lv D.W., Li R.;
RT "Conserved Herpesvirus Protein Kinases Target SAMHD1 to Facilitate Virus
RT Replication.";
RL Cell Rep. 28:449-459(2019).
CC -!- FUNCTION: Plays many key roles by phosphorylating several proteins
CC including the viral DNA processivity factor BMRF1, EBNA1 or EBNA2.
CC Modifies the host nuclear envelope structure and induces the
CC redistribution of nuclear envelope-associated proteins by
CC phosphorylating host nucleoporins. Subsequently, promotes the nuclear
CC transport of EBV lytic proteins. Required for efficient lytic DNA
CC replication and release of nucleocapsids from the nucleus. Contributes
CC to the compaction of host cell chromatin in cells undergoing lytic
CC replication, presumably by phosphorylating the host condensin complex
CC and host TOP2A. Induces disassembly of the nuclear lamina by
CC phosphorylating with host LMNA. Phosphorylates substrates involved in
CC capsid assembly and DNA packaging. Facilitates the switch from latent
CC to lytic DNA replication by down-regulating EBNA1 replication function.
CC Phosphorylates the viral immediate-early protein BZLF1 and inhibits its
CC sumoylation by interacting with host SUMO1 and SUMO2. Phosphorylates
CC also host SAMHD1 and thereby counteracts its antiviral effect by
CC reducing its dNTP hydrolase activity. {ECO:0000269|PubMed:16698993,
CC ECO:0000269|PubMed:17360754, ECO:0000269|PubMed:17360761,
CC ECO:0000269|PubMed:18815303, ECO:0000269|PubMed:19244323,
CC ECO:0000269|PubMed:22398289, ECO:0000269|PubMed:22623767,
CC ECO:0000269|PubMed:25410863, ECO:0000269|PubMed:31291580}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:31291580};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:31291580};
CC -!- SUBUNIT: Interacts with host NUP62 and NUP153; this interaction plays a
CC role in nuclear targeting of BGLF4. Interacts with host SUMO1 and
CC SUMO2. {ECO:0000269|PubMed:22398289, ECO:0000269|PubMed:22623767}.
CC -!- INTERACTION:
CC P13288; Q01831: XPC; Xeno; NbExp=9; IntAct=EBI-1630636, EBI-372610;
CC -!- SUBCELLULAR LOCATION: Virion tegument. Host nucleus
CC {ECO:0000269|PubMed:22398289, ECO:0000269|PubMed:22623767}. Note=the
CC protein is present at discrete sites in nuclei, called replication
CC compartments where viral DNA replication occurs.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA24828.1; Type=Erroneous initiation; Evidence={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; CAA24828.1; ALT_INIT; Genomic_DNA.
DR EMBL; AJ507799; CAD53438.2; -; Genomic_DNA.
DR PIR; S33033; S33033.
DR RefSeq; YP_401688.1; NC_007605.1.
DR BioGRID; 971746; 3.
DR IntAct; P13288; 3.
DR MINT; P13288; -.
DR PRIDE; P13288; -.
DR DNASU; 3783704; -.
DR GeneID; 3783704; -.
DR KEGG; vg:3783704; -.
DR SIGNOR; P13288; -.
DR Proteomes; UP000153037; Genome.
DR GO; GO:0044199; C:host cell nuclear envelope; IDA:CACAO.
DR GO; GO:0042025; C:host cell nucleus; IMP:CACAO.
DR GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0039525; P:modulation by virus of host chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Early protein; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host IRF3 by virus; Inhibition of host RLR pathway by virus;
KW Kinase; Modulation of host chromatin by virus; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Viral immunoevasion; Virion; Virion tegument.
FT CHAIN 1..429
FT /note="Serine/threonine-protein kinase BGLF4"
FT /id="PRO_0000086184"
FT DOMAIN 1..409
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 36..40
FT /note="SUMO interaction motif"
FT /evidence="ECO:0000269|PubMed:22398289"
FT REGION 344..350
FT /note="SUMO interaction motif"
FT /evidence="ECO:0000269|PubMed:22398289"
FT COMPBIAS 7..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 195
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 110..118
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 128
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 429 AA; 48351 MW; 241ECF46F613A68B CRC64;
MDVNMAAELS PTNSSSSGEL SVSPEPPRET QAFLGKVTVI DYFTFQHKHL KVTNIDDMTE
TLYVKLPENM TRCDHLPITC EYLLGRGSYG AVYAHADNAT VKLYDSVTEL YHELMVCDMI
QIGKATAEDG QDKALVDYLS ACTSCHALFM PQFRCSLQDY GHWHDGSIEP LVRGFQGLKD
AVYFLNRHCG LFHSDISPSN ILVDFTDTMW GMGRLVLTDY GTASLHDRNK MLDVRLKSSK
GRQLYRLYCQ REPFSIAKDT YKPLCLLSKC YILRGAGHIP DPSACGPVGA QTALRLDLQS
LGYSLLYGIM HLADSTHKIP YPNPDMGFDR SDPLYFLQFA APKVVLLEVL SQMWNLNLDM
GLTSCGESPC VDVTAEHMSQ FLQWCRSLKK RFKESYFFNC RPRFEHPHLP GLVAELLADD
FFGPDGRRG
