VPK_HHV8P
ID VPK_HHV8P Reviewed; 444 AA.
AC F5HGH5;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Viral protein kinase;
DE EC=2.7.11.1 {ECO:0000269|PubMed:31291580};
GN Name=vPK; ORFNames=ORF36;
OS Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's
OS sarcoma-associated herpesvirus).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Rhadinovirus.
OX NCBI_TaxID=868565;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10400794; DOI=10.1128/jvi.73.8.6953-6963.1999;
RA Glenn M., Rainbow L., Aurade F., Davison A., Schulz T.F.;
RT "Identification of a spliced gene from Kaposi's sarcoma-associated
RT herpesvirus encoding a protein with similarities to latent membrane
RT proteins 1 and 2A of Epstein-Barr virus.";
RL J. Virol. 73:6953-6963(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16760382; DOI=10.1099/vir.0.81919-0;
RA Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.;
RT "Kaposi's sarcoma-associated herpesvirus immune modulation: an overview.";
RL J. Gen. Virol. 87:1781-1804(2006).
RN [3]
RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF LYS-108.
RX PubMed=10725434; DOI=10.1099/0022-1317-81-4-1067;
RA Park J., Lee D., Seo T., Chung J., Choe J.;
RT "Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) open reading
RT frame 36 protein is a serine protein kinase.";
RL J. Gen. Virol. 81:1067-1071(2000).
RN [4]
RP FUNCTION.
RX PubMed=15247271; DOI=10.1074/jbc.m400964200;
RA Hamza M.S., Reyes R.A., Izumiya Y., Wisdom R., Kung H.J., Luciw P.A.;
RT "ORF36 protein kinase of Kaposi's sarcoma herpesvirus activates the c-Jun
RT N-terminal kinase signaling pathway.";
RL J. Biol. Chem. 279:38325-38330(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH PROTEIN K8.
RX PubMed=17108053; DOI=10.1128/jvi.01473-06;
RA Izumiya Y., Izumiya C., Van Geelen A., Wang D.H., Lam K.S., Luciw P.A.,
RA Kung H.J.;
RT "Kaposi's sarcoma-associated herpesvirus-encoded protein kinase and its
RT interaction with K-bZIP.";
RL J. Virol. 81:1072-1082(2007).
RN [6]
RP FUNCTION.
RX PubMed=23530827; DOI=10.4149/av_2013_01_75;
RA Kim S., Cha S., Jang J.H., Kim Y., Seo T.;
RT "Kaposis sarcoma-associated herpesvirus ORF36 protein induces chromosome
RT condensation and phosphorylation of histone H3.";
RL Acta Virol. 57:75-79(2013).
RN [7]
RP FUNCTION.
RX PubMed=23678174; DOI=10.1128/jvi.03460-12;
RA McDowell M.E., Purushothaman P., Rossetto C.C., Pari G.S., Verma S.C.;
RT "Phosphorylation of Kaposi's Sarcoma-Associated Herpesvirus processivity
RT factor ORF59 by a viral kinase modulates its ability to associate with RTA
RT and oriLyt.";
RL J. Virol. 87:8038-8052(2013).
RN [8]
RP FUNCTION, AND INTERACTION WITH HOST BETA-CATENIN/CTNNB1.
RX PubMed=29432739; DOI=10.1016/j.bbrc.2018.02.089;
RA Cha S., Kang M.S., Seo T.;
RT "KSHV vPK inhibits Wnt signaling via preventing interactions between beta-
RT catenin and TCF4.";
RL Biochem. Biophys. Res. Commun. 497:381-387(2018).
RN [9]
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: Serine/threonine protein kinase that plays a role in viral
CC gene expression, viral DNA replication and encapsidation, and nuclear
CC egress of virions. Regulates host transcriptional activity through
CC interactions with RNA helicase and c-Jun N-terminal kinase (JNK) and
CC viral transcriptional activity through interactions with the viral
CC protein K-bZIP/K8 (PubMed:17108053). Induces host chromosome
CC condensation and phosphorylation of histone H3. Phosphorylates the DNA
CC polymerase processivity factor hence modulating its processivity
CC function. Inhibits the host Wnt signaling pathway via direct
CC interactions with beta-catenin/CTNNB1 while the kinase activity of vPK
CC is not required for this inhibitory activity. Phosphorylates also host
CC SAMHD1 and thereby counteracts its antiviral effect by reducing its
CC dNTP hydrolase activity. {ECO:0000269|PubMed:10725434,
CC ECO:0000269|PubMed:15247271, ECO:0000269|PubMed:17108053,
CC ECO:0000269|PubMed:23530827, ECO:0000269|PubMed:23678174,
CC ECO:0000269|PubMed:29432739, 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 protein K-bZIP/K8 (PubMed:17108053). Interacts
CC with host beta-catenin/CTNNB1 (PubMed:29432739).
CC {ECO:0000269|PubMed:17108053, ECO:0000269|PubMed:29432739}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:10725434}.
CC -!- PTM: AUtophosphorylated.
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DR EMBL; AF148805; ABD28887.1; -; Genomic_DNA.
DR RefSeq; YP_001129389.1; NC_009333.1.
DR BioGRID; 1777007; 3.
DR PRIDE; F5HGH5; -.
DR DNASU; 4961434; -.
DR GeneID; 4961434; -.
DR GeneID; 4961504; -.
DR KEGG; vg:4961434; -.
DR Proteomes; UP000000942; Genome.
DR GO; GO:0042025; C:host cell nucleus; 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-EC.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Host nucleus; Kinase; Nucleotide-binding; Reference proteome;
KW Transferase.
FT CHAIN 1..444
FT /note="Viral protein kinase"
FT /id="PRO_0000423845"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 201
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 90..98
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 108
FT /note="K->Q: Complete loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10725434"
SQ SEQUENCE 444 AA; 50335 MW; 589B2617E3900D80 CRC64;
MRWKRMERRP PLTPLRRSRT QSSGGGLTIC PRCALKLPKA TRISERPWAS TWQLNQHIQV
SKTKKATAYL KAPREWGQCT HQDPDWSKRL GRGAFGIIVP ISEDLCVKQF DSRREFFYEA
IANDLMQATR ERYPMHSGGS RLLGFVQPCI PCRSIVYPRM KCNLLQLDWS QVNLSVMAAE
FTGLMAAVSF LNRYCGMVHC DVSPDNILAT GDLTPMNPGR LVLTDFGSVA LHSGSKWTNL
VVTSNLGFKQ HCYDFRVPPK LICKHLYKPS CVLFQCYLSS LGKMHAQVLD QPYPISPNMG
LTIDMSSLGY TLLTCLELYL DLPLNNPLKF LGSATRDGRP EPMYYLGFMI PRVVMTQILS
AVWTMTLDLG LDCTGKAQAI PMRQEHQLAF QKQCYLYKAN QKAESLANCS DKLNCPMLKS
LVRKLLERDF FNHGGHPHTR GLVF
