KITH_HHV11
ID KITH_HHV11 Reviewed; 376 AA.
AC P0DTH5; A0A5J6DX09; G8HBD6; P03176;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 03-AUG-2022, entry version 5.
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 17) (HHV-1) (Human herpes simplex virus 1).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Alphaherpesvirinae; Simplexvirus.
OX NCBI_TaxID=10299;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17;
RX PubMed=2839594; DOI=10.1099/0022-1317-69-7-1531;
RA McGeoch D.J., Dalrymple M.A., Davison A.J., Dolan A., Frame M.C., McNab D.,
RA Perry L.J., Scott J.E., Taylor P.;
RT "The complete DNA sequence of the long unique region in the genome of
RT herpes simplex virus type 1.";
RL J. Gen. Virol. 69:1531-1574(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17;
RX PubMed=22417106; DOI=10.1111/j.1749-6632.2011.06358.x;
RA Davison A.J.;
RT "Evolution of sexually transmitted and sexually transmissible human
RT herpesviruses.";
RL Ann. N. Y. Acad. Sci. 1230:E37-E49(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Isolate S17pp, Isolate S17pp22a, Isolate S17pp3, Isolate S17pp4,
RC Isolate S17pp5, and Isolate S17pp8;
RA Jones J., Depledge D., Breuer J., Ebert-Keel K., Elliott G.;
RT "Genetic and phenotypic intrastrain variation in herpes simplex virus type
RT 1 Glasgow strain 17 syn+ derived viruses.";
RL Submitted (JUL-2019) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=17;
RX PubMed=32341360; DOI=10.1038/s41467-020-15992-5;
RA Whisnant A.W., Jurges C.S., Hennig T., Wyler E., Prusty B., Rutkowski A.J.,
RA L'hernault A., Djakovic L., Gobel M., Doring K., Menegatti J., Antrobus R.,
RA Matheson N.J., Kunzig F.W.H., Mastrobuoni G., Bielow C., Kempa S.,
RA Liang C., Dandekar T., Zimmer R., Landthaler M., Grasser F., Lehner P.J.,
RA Friedel C.C., Erhard F., Dolken L.;
RT "Integrative functional genomics decodes herpes simplex virus 1.";
RL Nat. Commun. 11:2038-2038(2020).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-376.
RX PubMed=7628623; DOI=10.1016/0014-5793(95)00680-8;
RA Wild K., Bohner T., Aubry A., Folkers G., Schulz G.E.;
RT "The three-dimensional structure of thymidine kinase from herpes simplex
RT virus type 1.";
RL FEBS Lett. 368:289-292(1995).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=7552712; DOI=10.1038/nsb1095-876;
RA Brown D.G., Visse R., Sandhu G., Davies A., Rizkallah P.J., Melitz C.,
RA Summers W.C., Sanderson M.R.;
RT "Crystal structures of the thymidine kinase from herpes simplex virus type-
RT 1 in complex with deoxythymidine and ganciclovir.";
RL Nat. Struct. Biol. 2:876-881(1995).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 34-376.
RX PubMed=9336833; DOI=10.1002/pro.5560061005;
RA Wild K., Bohner T., Folkers G., Schulz G.E.;
RT "The structures of thymidine kinase from herpes simplex virus type 1 in
RT complex with substrates and a substrate analogue.";
RL Protein Sci. 6:2097-2106(1997).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=9715911;
RX DOI=10.1002/(sici)1097-0134(19980815)32:3<350::aid-prot10>3.0.co;2-8;
RA Champness J.N., Bennett M.S., Wien F., Visse R., Summers W.C.,
RA Herdewijn P., de Clerq E., Ostrowski T., Jarvest R.L., Sanderson M.R.;
RT "Exploring the active site of herpes simplex virus type-1 thymidine kinase
RT by X-ray crystallography of complexes with aciclovir and other ligands.";
RL Proteins 32:350-361(1998).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=9989588; DOI=10.1016/s0014-5793(98)01619-6;
RA Bennett M.S., Wien F., Champness J.N., Batuwangala T., Rutherford T.,
RA Summers W.C., Sun H., Wright G., Sanderson M.R.;
RT "Structure to 1.9-A resolution of a complex with herpes simplex virus type-
RT 1 thymidine kinase of a novel, non-substrate inhibitor: X-ray
RT crystallographic comparison with binding of aciclovir.";
RL FEBS Lett. 443:121-125(1999).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 45-376 IN COMPLEX WITH ADENINE
RP ANALOG, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=11056041;
RX DOI=10.1002/1097-0134(20001201)41:4<545::aid-prot110>3.0.co;2-8;
RA Vogt J., Perozzo R., Pautsch A., Prota A., Schelling P., Pilger B.,
RA Folkers G., Scapozza L., Schulz G.E.;
RT "Nucleoside binding site of herpes simplex type 1 thymidine kinase analyzed
RT by X-ray crystallography.";
RL Proteins 41:545-553(2000).
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}.
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 ECO:0000269|PubMed:11056041};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04029,
CC ECO:0000269|PubMed:11056041}.
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}.
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DR EMBL; X14112; CAA32315.1; -; Genomic_DNA.
DR EMBL; JN555585; AEQ77053.1; -; Genomic_DNA.
DR EMBL; MN159376; QEU44927.1; -; Genomic_DNA.
DR EMBL; MN159377; QEU45002.1; -; Genomic_DNA.
DR EMBL; MN159378; QEU45078.1; -; Genomic_DNA.
DR EMBL; MN159379; QEU45154.1; -; Genomic_DNA.
DR EMBL; MN159381; QEU45306.1; -; Genomic_DNA.
DR EMBL; MN159382; QEU45382.1; -; Genomic_DNA.
DR EMBL; BK012101; DAC85562.1; -; Genomic_DNA.
DR PIR; E30084; KIBE17.
DR RefSeq; YP_009137097.1; NC_001806.2.
DR PDB; 1E2H; X-ray; 1.90 A; A/B=46-376.
DR PDB; 1E2I; X-ray; 1.90 A; A/B=46-376.
DR PDB; 1E2J; X-ray; 2.50 A; A/B=46-376.
DR PDB; 1E2K; X-ray; 1.70 A; A/B=46-376.
DR PDB; 1E2L; X-ray; 2.40 A; A/B=46-376.
DR PDB; 1E2M; X-ray; 2.20 A; A/B=46-376.
DR PDB; 1E2N; X-ray; 2.20 A; A/B=46-376.
DR PDB; 1E2P; X-ray; 2.50 A; A/B=46-376.
DR PDB; 1KI2; X-ray; 2.20 A; A/B=46-376.
DR PDB; 1KI3; X-ray; 2.37 A; A/B=46-376.
DR PDB; 1KI4; X-ray; 2.34 A; A/B=46-376.
DR PDB; 1KI6; X-ray; 2.37 A; A/B=46-376.
DR PDB; 1KI7; X-ray; 2.20 A; A/B=46-376.
DR PDB; 1KI8; X-ray; 2.20 A; A/B=46-376.
DR PDB; 1KIM; X-ray; 2.14 A; A/B=11-376.
DR PDB; 1OF1; X-ray; 1.95 A; A/B=1-376.
DR PDB; 1P7C; X-ray; 2.10 A; A/B=34-376.
DR PDB; 1QHI; X-ray; 1.90 A; A/B=11-376.
DR PDB; 1VTK; X-ray; 2.75 A; A=34-376.
DR PDB; 2KI5; X-ray; 1.90 A; A/B=11-376.
DR PDB; 2VTK; X-ray; 2.80 A; A=34-376.
DR PDB; 3F0T; X-ray; 2.00 A; A/B=45-376.
DR PDB; 3RDP; X-ray; 2.80 A; A/B=46-376.
DR PDB; 3VTK; X-ray; 3.00 A; A=34-376.
DR PDB; 4IVP; X-ray; 2.10 A; A/B=46-376.
DR PDB; 4IVQ; X-ray; 1.90 A; A/B=46-376.
DR PDB; 4IVR; X-ray; 2.40 A; A/B=46-376.
DR PDB; 4JBX; X-ray; 2.10 A; A/B=45-376.
DR PDB; 4JBY; X-ray; 2.00 A; A/B=45-376.
DR PDB; 4OQL; X-ray; 2.10 A; A/B=45-376.
DR PDB; 4OQM; X-ray; 2.20 A; A/B=45-376.
DR PDB; 4OQN; X-ray; 2.30 A; A/B=45-376.
DR PDB; 4OQX; X-ray; 2.50 A; A/B=45-376.
DR PDBsum; 1E2H; -.
DR PDBsum; 1E2I; -.
DR PDBsum; 1E2J; -.
DR PDBsum; 1E2K; -.
DR PDBsum; 1E2L; -.
DR PDBsum; 1E2M; -.
DR PDBsum; 1E2N; -.
DR PDBsum; 1E2P; -.
DR PDBsum; 1KI2; -.
DR PDBsum; 1KI3; -.
DR PDBsum; 1KI4; -.
DR PDBsum; 1KI6; -.
DR PDBsum; 1KI7; -.
DR PDBsum; 1KI8; -.
DR PDBsum; 1KIM; -.
DR PDBsum; 1OF1; -.
DR PDBsum; 1P7C; -.
DR PDBsum; 1QHI; -.
DR PDBsum; 1VTK; -.
DR PDBsum; 2KI5; -.
DR PDBsum; 2VTK; -.
DR PDBsum; 3F0T; -.
DR PDBsum; 3RDP; -.
DR PDBsum; 3VTK; -.
DR PDBsum; 4IVP; -.
DR PDBsum; 4IVQ; -.
DR PDBsum; 4IVR; -.
DR PDBsum; 4JBX; -.
DR PDBsum; 4JBY; -.
DR PDBsum; 4OQL; -.
DR PDBsum; 4OQM; -.
DR PDBsum; 4OQN; -.
DR PDBsum; 4OQX; -.
DR SMR; P0DTH5; -.
DR GeneID; 24271467; -.
DR KEGG; vg:24271467; -.
DR Proteomes; UP000009294; Genome.
DR Proteomes; UP000180758; Genome.
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 3D-structure; ATP-binding; DNA synthesis; Early protein; Kinase;
KW Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..376
FT /note="Thymidine kinase"
FT /id="PRO_0000175069"
FT REGION 1..38
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 STRAND 48..54
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:2KI5"
FT HELIX 62..69
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:2VTK"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:4IVP"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 85..89
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 96..108
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 114..139
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:1KI2"
FT STRAND 156..162
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 165..169
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 171..178
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 184..192
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:1E2K"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:1KI8"
FT HELIX 229..250
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:4IVQ"
FT HELIX 306..320
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 323..328
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 333..343
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:1E2K"
FT STRAND 349..354
FT /evidence="ECO:0007829|PDB:1E2K"
FT HELIX 357..372
FT /evidence="ECO:0007829|PDB:1E2K"
SQ SEQUENCE 376 AA; 40921 MW; 5128181FBF08DA50 CRC64;
MASYPCHQHA SAFDQAARSR GHNNRRTALR PRRQQKATEV RLEQKMPTLL RVYIDGPHGM
GKTTTTQLLV ALGSRDDIVY VPEPMTYWRV LGASETIANI YTTQHRLDQG EISAGDAAVV
MTSAQITMGM PYAVTDAVLA PHIGGEAGSS HAPPPALTLI FDRHPIAALL CYPAARYLMG
SMTPQAVLAF VALIPPTLPG TNIVLGALPE DRHIDRLAKR QRPGERLDLA MLAAIRRVYG
LLANTVRYLQ GGGSWREDWG QLSGAAVPPQ GAEPQSNAGP RPHIGDTLFT LFRAPELLAP
NGDLYNVFAW ALDVLAKRLR PMHVFILDYD QSPAGCRDAL LQLTSGMVQT HVTTPGSIPT
ICDLARTFAR EMGEAN
