KITH_HHV1K
ID KITH_HHV1K Reviewed; 376 AA.
AC P17402;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Thymidine kinase {ECO:0000255|HAMAP-Rule:MF_04029};
DE EC=2.7.1.21 {ECO:0000255|HAMAP-Rule:MF_04029};
GN Name=TK {ECO:0000255|HAMAP-Rule:MF_04029}; OrderedLocusNames=UL23;
OS Human herpesvirus 1 (strain KOS) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10306;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2536979; DOI=10.1016/0042-6822(89)90260-2;
RA Irmiere A.F., Manos M.M., Jacobson J.G., Gibbs J.S., Coen D.M.;
RT "Effect of an amber mutation in the herpes simplex virus thymidine kinase
RT gene on polypeptide synthesis and stability.";
RL Virology 168:210-220(1989).
RN [2]
RP FUNCTION.
RX PubMed=2543985; DOI=10.1073/pnas.86.12.4736;
RA Coen D.M., Kosz-Vnenchak M., Jacobson J.G., Leib D.A., Bogard C.L.,
RA Schaffer P.A., Tyler K.L., Knipe D.M.;
RT "Thymidine kinase-negative herpes simplex virus mutants establish latency
RT in mouse trigeminal ganglia but do not reactivate.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4736-4740(1989).
CC -!- FUNCTION: Catalyzes the transfer of the gamma-phospho group of ATP to
CC thymidine to generate dTMP in the salvage pathway of pyrimidine
CC synthesis. The dTMP serves as a substrate for DNA polymerase during
CC viral DNA replication. Allows the virus to be reactivated and to grow
CC in non-proliferative cells lacking a high concentration of
CC phosphorylated nucleic acid precursors. {ECO:0000255|HAMAP-
CC Rule:MF_04029, ECO:0000269|PubMed:2543985}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + thymidine = ADP + dTMP + H(+); Xref=Rhea:RHEA:19129,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17748, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:63528, ChEBI:CHEBI:456216; EC=2.7.1.21;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04029};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04029}.
CC -!- BIOTECHNOLOGY: Used in molecular biology as a selectable marker to
CC identify transfected eukaryotic cells. Used in cancer suicide gene
CC therapy to selectively kill transformed cells.
CC -!- MISCELLANEOUS: Phosphorylates and thereby activates certain drugs like
CC acyclovir (ACV), valacyclovir, and famciclovir to a toxic form, that
CC leads to successful suppression of the infection, while the uninfected
CC cell does not have this ability because it lacks TK. Mutations in
CC thymidine kinase may induce HSV resistance to antiviral therapies in
CC immunocompromised patients. The most frequently observed resistant
CC strains are unable to express TK and are avirulent in animal models of
CC disease. Resistance may be acquired less frequently by selecting
CC variants which no longer recognize ACV or ACV triphosphate as
CC substrates but which retain normal functions.
CC -!- SIMILARITY: Belongs to the herpesviridae thymidine kinase family.
CC {ECO:0000255|HAMAP-Rule:MF_04029}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA45817.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; J04327; AAA45817.1; ALT_INIT; Genomic_DNA.
DR PIR; A31291; KIBEKS.
DR SMR; P17402; -.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004797; F:thymidine kinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006230; P:TMP biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_04029; HSV_KITH; 1.
DR InterPro; IPR001889; Herpes_TK.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00693; Herpes_TK; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; DNA synthesis; Early protein; Kinase; Nucleotide-binding;
KW Transferase.
FT CHAIN 1..376
FT /note="Thymidine kinase"
FT /id="PRO_0000175072"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 83
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 56..63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 125
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 216
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 222
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT VARIANT 175
FT /note="A -> T (in mutant KG111)"
SQ SEQUENCE 376 AA; 40927 MW; 86BE4A947F9AB1C7 CRC64;
MASYPCHQHA SAFDQAARSR GHSNRRTALR PRRQQEATEV RLEQKMPTLL RVYIDGPHGM
GKTTTTQLLV ALGSRDDIVY VPEPMTYWQV LGASETIANI YTTQHRLDQG EISAGDAAVV
MTSAQITMGM PYAVTDAVLA PHIGGEAGSS HAPPPALTLI FDRHPIAALL CYPAARYLMG
SMTPQAVLAF VALIPPTLPG TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG
LLANTVRYLQ GGGSWREDWG QLSGTAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT HVTTPGSIPT
ICDLARMFAR EMGEAN
