UL97_HCMVT
ID UL97_HCMVT Reviewed; 707 AA.
AC Q68101;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Serine/threonine protein kinase UL97;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P16788};
DE AltName: Full=Ganciclovir kinase;
GN Name=UL97;
OS Human cytomegalovirus (strain Towne) (HHV-5) (Human herpesvirus 5).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Betaherpesvirinae; Cytomegalovirus.
OX NCBI_TaxID=10363;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11557468; DOI=10.1128/aac.45.10.2775-2780.2001;
RA Lurain N.S., Weinberg A., Crumpacker C.S., Chou S.;
RT "Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance
RT testing.";
RL Antimicrob. Agents Chemother. 45:2775-2780(2001).
CC -!- FUNCTION: Serine/threonine protein kinase that plays important roles in
CC several processes including nuclear viral egress, viral replication or
CC regulation of host cell cycle progression. Participates in the
CC acquisition of tegument during virion morphogenesis in the nucleus.
CC Redistributes the host nuclear lamina by phosphorylating cellular
CC Lamins-A/C. Plays a role in viral DNA synthesis by phosphorylating the
CC DNA polymerase processivity factor UL44. Stimulates host cell cycle to
CC support viral DNA synthesis by phosphorylating host retinoblastoma/RB1
CC protein. Additional substrates have been identified including host EF1D
CC or H2B. Phosphorylates also host SAMHD1 and thereby counteracts its
CC antiviral effect by reducing its dNTP hydrolase activity.
CC {ECO:0000250|UniProtKB:P16788}.
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:0000250|UniProtKB:P16788};
CC -!- SUBUNIT: Interacts with UL83. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000250}.
CC -!- PTM: Autophosphorylates on serine and threonine residues.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: Phosphorylates and thereby activates the antiviral
CC nucleoside analog ganciclovir used to treat CMV infections.
CC Phosphorylation transform the drug to a toxic form, that leads to
CC successful suppression of the infection, while the uninfected cell does
CC not have this ability because it lacks the viral kinase. Mutations in
CC phosphotransferase may induce CMV resistance to antiviral therapies in
CC immunocompromised patients.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. HCMV ganciclovir subfamily. {ECO:0000305}.
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DR EMBL; U07355; AAA16789.1; -; Unassigned_DNA.
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: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; IPR008266; Tyr_kinase_AS.
DR Pfam; PF06734; UL97; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 3: Inferred from homology;
KW ATP-binding; Host-virus interaction; Kinase;
KW Modulation of host cell cycle by virus; Nucleotide-binding; Transferase;
KW Virion.
FT CHAIN 1..707
FT /note="Serine/threonine protein kinase UL97"
FT /id="PRO_0000088193"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 176..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..260
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 456
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 337..345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 359
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
SQ SEQUENCE 707 AA; 78248 MW; B09B1DE3D7113F13 CRC64;
MSSALRSRAR SASLGTTTEG WDPPPLRRPS RARRRQWMRE AAQAAAQAAV QAAQAAAAQV
AQAHVDEDEV VDLMADEAGG GVTTLTTLSS VSTTTVLGHA TFSACVRNDV MRDGEKEDAA
SDKENLRRPV VPSTSSRGSA ASGDGYHGLR CRETSAMWSF EYDRDGDVTS VRRALFTGGS
DPSDSVSGVR GGRKRPLRPP LVSLARTPLC RRRVGGVDAV LEENDVELRA ESQDSAVASG
PGRVPQPLSG SSGEESATAV EADSTSHDDV HCTCSNDQII TTSIRGLTCD PRMFLRLTHP
ELCELSISYL LVYVPKEDDF CHKICYAVDM SDESYRLGQG SFGEVWPLDR YRVVKVARKH
SETVLTVWMS GLIRTRAAGE QQQPPSLVGT GVHRGLLTAT GCCLLHNVTV HRRFHTDMFH
HDQWKLACID SYRRAFCTLA DAIKFLNHQC RVCHFDITPM NVLIDVNPHN PSEIVRAALC
DYSLSEPYPD YNERCVAVFQ ETGTARRIPN CSHRLRECYH PAFRPMPLQK LLICDPHARF
PVAGLRRYCM SELSALGNVL GFCLMRLLDR RGLDEVRMGT EALLFKHAGA ACRALENGKL
THCSDACLLI LAAQMSYGAC LLGEHGAALV SHTLRFVEAK MSSCRVRAFR RFYHECSQTM
LHEYVRKNVE RLLATSDGLY LYNAFRRTTS IICEEDLDGD CRQLFPE
