UL97_MUHVS
ID UL97_MUHVS Reviewed; 643 AA.
AC D3XDS2;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Serine/threonine protein kinase M97 {ECO:0000303|PubMed:17910700};
DE EC=2.7.11.1 {ECO:0000269|PubMed:31548683};
GN Name=M97;
OS Murid herpesvirus 1 (strain Smith) (MuHV-1) (Mouse cytomegalovirus).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Muromegalovirus.
OX NCBI_TaxID=10367;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Smith;
RX PubMed=20015993; DOI=10.1128/jvi.02142-09;
RA Cheng T.P., Valentine M.C., Gao J., Pingel J.T., Yokoyama W.M.;
RT "Stability of murine cytomegalovirus genome after in vitro and in vivo
RT passage.";
RL J. Virol. 84:2623-2628(2010).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17910700; DOI=10.1111/j.1365-2818.2007.01825.x;
RA Buser C., Fleischer F., Mertens T., Michel D., Schmidt V., Walther P.;
RT "Quantitative investigation of murine cytomegalovirus nucleocapsid
RT interaction.";
RL J. Microsc. 228:78-87(2007).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-290.
RX PubMed=31548683; DOI=10.1038/s41564-019-0529-z;
RA Deutschmann J., Schneider A., Gruska I., Vetter B., Thomas D.,
RA Kiessling M., Wittmann S., Herrmann A., Schindler M., Milbradt J.,
RA Ferreiros N., Winkler T.H., Wiebusch L., Gramberg T.;
RT "A viral kinase counteracts in vivo restriction of murine cytomegalovirus
RT by SAMHD1.";
RL Nat. Microbiol. 4:2273-2284(2019).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, INTERACTION
RP WITH HOST CCNA2, AND MUTAGENESIS OF ARG-45; LEU-47 AND PHE-49.
RX PubMed=32973148; DOI=10.1038/s41467-020-18542-1;
RA Bogdanow B., Schmidt M., Weisbach H., Gruska I., Vetter B., Imami K.,
RA Ostermann E., Brune W., Selbach M., Hagemeier C., Wiebusch L.;
RT "Cross-regulation of viral kinases with cyclin A secures shutoff of host
RT DNA synthesis.";
RL Nat. Commun. 11:4845-4845(2020).
CC -!- FUNCTION: Serine/threonine protein kinase that plays important roles in
CC several processes including viral morphogenesis, nuclear viral egress,
CC viral replication or regulation of host cell cycle progression
CC (PubMed:17910700, PubMed:32973148). Participates in the acquisition of
CC tegument during virion morphogenesis in the nucleus (By similarity).
CC Phosphorylates host SAMHD1 and thereby counteracts its antiviral effect
CC by reducing its dNTP hydrolase activity (PubMed:31548683). Inhibits
CC host DNA synthesis by cyclin A/CDKN2A sequestration to the cytoplasm
CC (PubMed:32973148). {ECO:0000250|UniProtKB:P16788,
CC ECO:0000269|PubMed:17910700, ECO:0000269|PubMed:31548683,
CC ECO:0000269|PubMed:32973148}.
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:0000250|UniProtKB:P16788};
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:31548683};
CC -!- SUBUNIT: Interacts with host CCNA2; this interaction sequesters CCNA2
CC to the cytoplasm. {ECO:0000269|PubMed:32973148}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P16788}. Host
CC nucleus {ECO:0000269|PubMed:32973148}. Host cytoplasm
CC {ECO:0000269|PubMed:32973148}. Note=Present in host nucleus at early
CC times but redistributes to a predominantly cytoplasmic localization
CC pattern at 24 hours post infection. {ECO:0000269|PubMed:32973148}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutants show a loss of typical
CC nucleocapsid clustering in host-infected nuclei.
CC {ECO:0000269|PubMed:17910700}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. HCMV ganciclovir subfamily. {ECO:0000305}.
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DR EMBL; GU305914; ADD10466.1; -; Genomic_DNA.
DR Proteomes; UP000180711; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0060153; P:modulation by virus of host cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR InterPro; IPR010615; Herpes_UL97.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR Pfam; PF06734; UL97; 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; Host cytoplasm; Host nucleus; Host-virus interaction; Kinase;
KW Modulation of host cell cycle by virus; Nucleotide-binding; Transferase;
KW Virion.
FT CHAIN 1..643
FT /note="Serine/threonine protein kinase M97"
FT /id="PRO_0000451907"
FT DOMAIN 265..643
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 25..49
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:32973148"
FT REGION 52..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 155..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..77
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..96
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..182
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 391
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 271..279
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 290
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 45
FT /note="R->A: Complete nuclear localization; when associated
FT with A-47."
FT /evidence="ECO:0000269|PubMed:32973148"
FT MUTAGEN 47
FT /note="L->A: Complete nuclear localization; when associated
FT with A-45."
FT /evidence="ECO:0000269|PubMed:32973148"
FT MUTAGEN 47
FT /note="L->A: Complete nuclear localization; when associated
FT with A-49."
FT /evidence="ECO:0000269|PubMed:32973148"
FT MUTAGEN 49
FT /note="F->A: Complete nuclear localization; when associated
FT with A-47."
FT /evidence="ECO:0000269|PubMed:32973148"
FT MUTAGEN 290
FT /note="K->Q: Complete loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:31548683"
SQ SEQUENCE 643 AA; 71158 MW; A03A399949C8A371 CRC64;
MSVELTPPRS DGSVGFAPVV VPPAPRKPLR RRAVSDLEKL YKVKRRLVFG ADDGAVDNDT
SNNNSGSSST TSRSRRKTAA DVVSDSPKRT DDSSTAGEDG YTHCVHSCAC TPGERHLLCC
ELVSIGDSVS VARCPLCSLG ISTTYLSRGC CRGRSKVTGG DEDEEDEDEE ENSQDEDRDE
EEAASASSSG GLEWSDDSNS ALSWSDENII ISPFPGLKCY VTTFEDIRQP VLLETGSAYL
PVYVPYDESF CRNRCLERGG DDDDERDATL IGKGSFGQVW RLSDKKTALK AAASESINET
LLTVWISGVV RSRAQDAGYR GELDDSVYCN ILVATGSCLR HNLVSFASFD RDLYNYRGWH
YAGLASYRRA FSGIADALRF LNLRCGVGHF DVTPMNVLIN YDRADDRQIA RAVICDFSLS
QCHTEGTTGH CVVVFQQTKT VRALPKSAYY LTDIYHPAFK PLMLQKLCAI EPRKQFPKPS
ANRFCVSDLC ALGHVAAFCL VRVLDERGQL KVRSTSEDAL FGVARKTCDA LARHSVDEVA
NFCSLLITRQ LAYTATLLGS DDMREPMARL CDYFETVSDK DAPDRFRSVY KRARREIDGS
YMVRLLLAAS ETEDGRYLLD NIRATCLMVD SEDLDVDPYK IFP
