KITM_HUMAN
ID KITM_HUMAN Reviewed; 265 AA.
AC O00142; B4DGJ7; B4DZK7; B7ZAB1; E5KNQ5; E9PH08; O15238;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 4.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Thymidine kinase 2, mitochondrial {ECO:0000305};
DE EC=2.7.1.21 {ECO:0000269|PubMed:11687801, ECO:0000269|PubMed:9989599};
DE AltName: Full=2'-deoxyuridine kinase TK2 {ECO:0000305};
DE EC=2.7.1.74 {ECO:0000305|PubMed:9989599};
DE AltName: Full=Deoxycytidine kinase TK2 {ECO:0000305};
DE EC=2.7.1.- {ECO:0000269|PubMed:11687801, ECO:0000305|PubMed:9989599};
DE AltName: Full=Mt-TK;
DE Flags: Precursor;
GN Name=TK2 {ECO:0000303|PubMed:9989599, ECO:0000312|HGNC:HGNC:11831};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=9079672; DOI=10.1074/jbc.272.13.8454;
RA Johansson M., Karlsson A.;
RT "Cloning of the cDNA and chromosome localization of the gene for human
RT thymidine kinase 2.";
RL J. Biol. Chem. 272:8454-8458(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 34-61 (ISOFORM
RP 1), FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=9989599; DOI=10.1016/s0014-5793(98)01711-6;
RA Wang L., Munch-Petersen B., Herrstroem Sjoeberg A., Hellman U., Bergman T.,
RA Joernvall H., Eriksson S.;
RT "Human thymidine kinase 2: molecular cloning and characterisation of the
RT enzyme activity with antiviral and cytostatic nucleoside substrates.";
RL FEBS Lett. 443:170-174(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 6), AND SUBUNIT.
RX PubMed=20843780; DOI=10.1093/nar/gkq750;
RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R.,
RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M.,
RA Speed T.P., Scharfe C.;
RT "Identification of rare DNA variants in mitochondrial disorders with
RT improved array-based sequencing.";
RL Nucleic Acids Res. 39:44-58(2011).
RN [4]
RP SEQUENCE REVISION.
RA Wang L.;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5).
RC TISSUE=Brain, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP VARIANTS MTDPS2 ASN-121 AND ASN-212, FUNCTION, CATALYTIC ACTIVITY, AND
RP CHARACTERIZATION OF VARIANTS MTDPS2 ASN-121 AND ASN-212.
RX PubMed=11687801; DOI=10.1038/ng751;
RA Saada A., Shaag A., Mandel H., Nevo Y., Eriksson S., Elpeleg O.;
RT "Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion
RT myopathy.";
RL Nat. Genet. 29:342-344(2001).
RN [10]
RP VARIANTS MTDPS2 MET-53; MET-108 AND ASN-121.
RX PubMed=12391347; DOI=10.1212/01.wnl.0000028689.93049.9a;
RA Mancuso M., Salviati L., Sacconi S., Otaegui D., Camano P., Marina A.,
RA Bacman S., Moraes C.T., Carlo J.R., Garcia M., Garcia-Alvarez M.,
RA Monzon L., Naini A.B., Hirano M., Bonilla E., Taratuto A.L., DiMauro S.,
RA Vu T.H.;
RT "Mitochondrial DNA depletion: mutations in thymidine kinase gene with
RT myopathy and SMA.";
RL Neurology 59:1197-1202(2002).
RN [11]
RP VARIANTS MTDPS2 MET-108 AND LYS-192, AND CHARACTERIZATION OF VARIANTS
RP MTDPS2 MET-108 AND LYS-192.
RX PubMed=15639197; DOI=10.1016/j.ymgme.2004.09.005;
RA Wang L., Limongelli A., Vila M.R., Carrara F., Zeviani M., Eriksson S.;
RT "Molecular insight into mitochondrial DNA depletion syndrome in two
RT patients with novel mutations in the deoxyguanosine kinase and thymidine
RT kinase 2 genes.";
RL Mol. Genet. Metab. 84:75-82(2005).
RN [12]
RP VARIANTS MTDPS2 MET-64 AND TRP-183.
RX PubMed=15907288; DOI=10.1016/j.nmd.2005.03.010;
RA Tulinius M., Moslemi A.-R., Darin N., Holme E., Oldfors A.;
RT "Novel mutations in the thymidine kinase 2 gene (TK2) associated with fatal
RT mitochondrial myopathy and mitochondrial DNA depletion.";
RL Neuromuscul. Disord. 15:412-415(2005).
RN [13]
RP INVOLVEMENT IN PEOB3, VARIANTS PEOB3 TRP-183 AND ALA-188, CHARACTERIZATION
RP OF VARIANTS PEOB3 TRP-183 AND ALA-188, AND SUBUNIT.
RX PubMed=21937588; DOI=10.1093/hmg/ddr438;
RA Tyynismaa H., Sun R., Ahola-Erkkilae S., Almusa H., Poeyhoenen R.,
RA Korpela M., Honkaniemi J., Isohanni P., Paetau A., Wang L., Suomalainen A.;
RT "Thymidine kinase 2 mutations in autosomal recessive progressive external
RT ophthalmoplegia with multiple mitochondrial DNA deletions.";
RL Hum. Mol. Genet. 21:66-75(2012).
RN [14]
RP VARIANTS MTDPS2 VAL-117 AND VAL-139.
RX PubMed=25446393; DOI=10.1016/j.mito.2014.10.007;
RA Knierim E., Seelow D., Gill E., von Moers A., Schuelke M.;
RT "Clinical application of whole exome sequencing reveals a novel compound
RT heterozygous TK2-mutation in two brothers with rapidly progressive combined
RT muscle-brain atrophy, axonal neuropathy, and status epilepticus.";
RL Mitochondrion 20:1-6(2015).
CC -!- FUNCTION: Phosphorylates thymidine, deoxycytidine, and deoxyuridine in
CC the mitochondrial matrix (PubMed:9989599, PubMed:11687801). In non-
CC replicating cells, where cytosolic dNTP synthesis is down-regulated,
CC mtDNA synthesis depends solely on TK2 and DGUOK (PubMed:9989599).
CC Widely used as target of antiviral and chemotherapeutic agents
CC (PubMed:9989599). {ECO:0000269|PubMed:11687801,
CC ECO:0000269|PubMed:9989599}.
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:0000269|PubMed:11687801, ECO:0000269|PubMed:9989599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19130;
CC Evidence={ECO:0000269|PubMed:11687801, ECO:0000269|PubMed:9989599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxycytidine + ATP = ADP + dCMP + H(+);
CC Xref=Rhea:RHEA:46040, ChEBI:CHEBI:15378, ChEBI:CHEBI:15698,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57566, ChEBI:CHEBI:456216;
CC EC=2.7.1.74; Evidence={ECO:0000269|PubMed:11687801,
CC ECO:0000305|PubMed:9989599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46041;
CC Evidence={ECO:0000269|PubMed:11687801, ECO:0000305|PubMed:9989599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyuridine + ATP = ADP + dUMP + H(+);
CC Xref=Rhea:RHEA:28206, ChEBI:CHEBI:15378, ChEBI:CHEBI:16450,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:246422, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000305|PubMed:9989599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28207;
CC Evidence={ECO:0000305|PubMed:9989599};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16 uM for thymidine {ECO:0000269|PubMed:9989599};
CC KM=36 uM for 2'-deoxycytidine {ECO:0000269|PubMed:9989599};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:20843780,
CC ECO:0000269|PubMed:21937588}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:9989599}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=O00142-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00142-2; Sequence=VSP_003028;
CC Name=3;
CC IsoId=O00142-3; Sequence=VSP_043503;
CC Name=4;
CC IsoId=O00142-4; Sequence=VSP_044459;
CC Name=5;
CC IsoId=O00142-5; Sequence=VSP_054606;
CC Name=6;
CC IsoId=O00142-6; Sequence=VSP_058694;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver, pancreas, muscle,
CC and brain. {ECO:0000269|PubMed:9079672}.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560]:
CC A disorder due to mitochondrial dysfunction characterized by childhood
CC onset of muscle weakness associated with depletion of mtDNA in skeletal
CC muscle. There is wide clinical variability; some patients have onset in
CC infancy and show a rapidly progressive course with early death due to
CC respiratory failure, whereas others have later onset of a slowly
CC progressive myopathy. {ECO:0000269|PubMed:11687801,
CC ECO:0000269|PubMed:12391347, ECO:0000269|PubMed:15639197,
CC ECO:0000269|PubMed:15907288, ECO:0000269|PubMed:25446393}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA
CC deletions, autosomal recessive 3 (PEOB3) [MIM:617069]: A form of
CC progressive external ophthalmoplegia, a mitochondrial myopathy
CC characterized by progressive paralysis of the levator palpebrae,
CC orbicularis oculi, and extraocular muscles. PEOB3 patients manifest
CC adult-onset progressive external ophthalmoplegia and progressive
CC proximal muscle weakness associated with muscle atrophy.
CC {ECO:0000269|PubMed:21937588}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DCK/DGK family.
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DR EMBL; U77088; AAC51167.1; -; mRNA.
DR EMBL; Y10498; CAA71523.3; -; mRNA.
DR EMBL; AK294627; BAG57808.1; -; mRNA.
DR EMBL; AK302976; BAG64119.1; -; mRNA.
DR EMBL; AK316226; BAH14597.1; -; mRNA.
DR EMBL; AC010542; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83013.1; -; Genomic_DNA.
DR EMBL; CH471092; EAW83015.1; -; Genomic_DNA.
DR EMBL; CH471092; EAW83017.1; -; Genomic_DNA.
DR EMBL; HQ205385; ADP90853.1; -; Genomic_DNA.
DR EMBL; HQ205382; ADP90850.1; -; Genomic_DNA.
DR EMBL; HQ205383; ADP90851.1; -; Genomic_DNA.
DR EMBL; HQ205384; ADP90852.1; -; Genomic_DNA.
DR EMBL; HQ205381; ADP90849.1; -; Genomic_DNA.
DR EMBL; HQ205380; ADP90848.1; -; Genomic_DNA.
DR EMBL; HQ205379; ADP90847.1; -; Genomic_DNA.
DR EMBL; HQ205378; ADP90846.1; -; Genomic_DNA.
DR EMBL; HQ205377; ADP90845.1; -; Genomic_DNA.
DR EMBL; HQ205376; ADP90844.1; -; Genomic_DNA.
DR EMBL; HQ205375; ADP90843.1; -; Genomic_DNA.
DR EMBL; HQ205374; ADP90842.1; -; Genomic_DNA.
DR EMBL; HQ205373; ADP90841.1; -; Genomic_DNA.
DR EMBL; HQ205372; ADP90840.1; -; Genomic_DNA.
DR EMBL; HQ205371; ADP90839.1; -; Genomic_DNA.
DR EMBL; HQ205370; ADP90838.1; -; Genomic_DNA.
DR EMBL; HQ205362; ADP90830.1; -; Genomic_DNA.
DR EMBL; HQ205363; ADP90831.1; -; Genomic_DNA.
DR EMBL; HQ205364; ADP90832.1; -; Genomic_DNA.
DR EMBL; HQ205365; ADP90833.1; -; Genomic_DNA.
DR EMBL; HQ205366; ADP90834.1; -; Genomic_DNA.
DR EMBL; HQ205367; ADP90835.1; -; Genomic_DNA.
DR EMBL; HQ205368; ADP90836.1; -; Genomic_DNA.
DR EMBL; HQ205369; ADP90837.1; -; Genomic_DNA.
DR EMBL; HQ205346; ADP90814.1; -; Genomic_DNA.
DR EMBL; HQ205347; ADP90815.1; -; Genomic_DNA.
DR EMBL; HQ205348; ADP90816.1; -; Genomic_DNA.
DR EMBL; HQ205349; ADP90817.1; -; Genomic_DNA.
DR EMBL; HQ205350; ADP90818.1; -; Genomic_DNA.
DR EMBL; HQ205351; ADP90819.1; -; Genomic_DNA.
DR EMBL; HQ205352; ADP90820.1; -; Genomic_DNA.
DR EMBL; HQ205353; ADP90821.1; -; Genomic_DNA.
DR EMBL; HQ205354; ADP90822.1; -; Genomic_DNA.
DR EMBL; HQ205355; ADP90823.1; -; Genomic_DNA.
DR EMBL; HQ205356; ADP90824.1; -; Genomic_DNA.
DR EMBL; HQ205357; ADP90825.1; -; Genomic_DNA.
DR EMBL; HQ205358; ADP90826.1; -; Genomic_DNA.
DR EMBL; HQ205359; ADP90827.1; -; Genomic_DNA.
DR EMBL; HQ205360; ADP90828.1; -; Genomic_DNA.
DR EMBL; HQ205361; ADP90829.1; -; Genomic_DNA.
DR CCDS; CCDS10805.2; -. [O00142-1]
DR CCDS; CCDS54016.1; -. [O00142-3]
DR CCDS; CCDS54017.1; -. [O00142-4]
DR CCDS; CCDS54018.1; -. [O00142-2]
DR CCDS; CCDS61955.1; -. [O00142-5]
DR RefSeq; NP_001166114.1; NM_001172643.1. [O00142-2]
DR RefSeq; NP_001166115.1; NM_001172644.1. [O00142-3]
DR RefSeq; NP_001258864.1; NM_001271935.1.
DR RefSeq; NP_001258979.1; NM_001272050.1. [O00142-5]
DR RefSeq; NP_004605.4; NM_004614.4. [O00142-1]
DR AlphaFoldDB; O00142; -.
DR SMR; O00142; -.
DR BioGRID; 112939; 16.
DR IntAct; O00142; 4.
DR STRING; 9606.ENSP00000299697; -.
DR BindingDB; O00142; -.
DR ChEMBL; CHEMBL4580; -.
DR DrugBank; DB02594; 2'-Deoxycytidine.
DR DrugBank; DB03312; Brivudine.
DR DrugBank; DB00441; Gemcitabine.
DR DrugBank; DB04485; Thymidine.
DR DrugBank; DB02452; Thymidine 5'-triphosphate.
DR DrugCentral; O00142; -.
DR iPTMnet; O00142; -.
DR PhosphoSitePlus; O00142; -.
DR BioMuta; TK2; -.
DR EPD; O00142; -.
DR jPOST; O00142; -.
DR MassIVE; O00142; -.
DR MaxQB; O00142; -.
DR PaxDb; O00142; -.
DR PeptideAtlas; O00142; -.
DR PRIDE; O00142; -.
DR ProteomicsDB; 20434; -.
DR ProteomicsDB; 47731; -. [O00142-1]
DR ProteomicsDB; 47732; -. [O00142-2]
DR ProteomicsDB; 47733; -. [O00142-3]
DR ProteomicsDB; 5605; -.
DR Antibodypedia; 29252; 69 antibodies from 16 providers.
DR DNASU; 7084; -.
DR Ensembl; ENST00000417693.8; ENSP00000407469.5; ENSG00000166548.17. [O00142-4]
DR Ensembl; ENST00000451102.7; ENSP00000414334.4; ENSG00000166548.17. [O00142-2]
DR Ensembl; ENST00000525974.5; ENSP00000434594.1; ENSG00000166548.17. [O00142-5]
DR Ensembl; ENST00000527800.6; ENSP00000433770.1; ENSG00000166548.17. [O00142-5]
DR Ensembl; ENST00000544898.6; ENSP00000440898.2; ENSG00000166548.17. [O00142-1]
DR Ensembl; ENST00000545043.6; ENSP00000438143.2; ENSG00000166548.17. [O00142-3]
DR Ensembl; ENST00000563369.6; ENSP00000463560.1; ENSG00000166548.17. [O00142-5]
DR Ensembl; ENST00000677420.1; ENSP00000504648.1; ENSG00000166548.17. [O00142-5]
DR Ensembl; ENST00000677555.1; ENSP00000503331.1; ENSG00000166548.17. [O00142-5]
DR Ensembl; ENST00000677715.1; ENSP00000502950.1; ENSG00000166548.17. [O00142-5]
DR Ensembl; ENST00000678015.1; ENSP00000502959.1; ENSG00000166548.17. [O00142-5]
DR Ensembl; ENST00000678297.1; ENSP00000503472.1; ENSG00000166548.17. [O00142-5]
DR GeneID; 7084; -.
DR KEGG; hsa:7084; -.
DR MANE-Select; ENST00000544898.6; ENSP00000440898.2; NM_004614.5; NP_004605.4.
DR UCSC; uc002eor.4; human. [O00142-1]
DR UCSC; uc059vic.1; human.
DR CTD; 7084; -.
DR DisGeNET; 7084; -.
DR GeneCards; TK2; -.
DR GeneReviews; TK2; -.
DR HGNC; HGNC:11831; TK2.
DR HPA; ENSG00000166548; Low tissue specificity.
DR MalaCards; TK2; -.
DR MIM; 188250; gene.
DR MIM; 609560; phenotype.
DR MIM; 617069; phenotype.
DR neXtProt; NX_O00142; -.
DR OpenTargets; ENSG00000166548; -.
DR Orphanet; 254886; Autosomal recessive progressive external ophthalmoplegia.
DR Orphanet; 254875; Mitochondrial DNA depletion syndrome, myopathic form.
DR PharmGKB; PA36535; -.
DR VEuPathDB; HostDB:ENSG00000166548; -.
DR eggNOG; KOG4235; Eukaryota.
DR GeneTree; ENSGT00940000158005; -.
DR HOGENOM; CLU_030466_1_0_1; -.
DR InParanoid; O00142; -.
DR OMA; TVICIEG; -.
DR PhylomeDB; O00142; -.
DR TreeFam; TF324413; -.
DR BioCyc; MetaCyc:HS09420-MON; -.
DR BRENDA; 2.7.1.21; 2681.
DR PathwayCommons; O00142; -.
DR Reactome; R-HSA-73614; Pyrimidine salvage.
DR SABIO-RK; O00142; -.
DR SignaLink; O00142; -.
DR BioGRID-ORCS; 7084; 10 hits in 1082 CRISPR screens.
DR ChiTaRS; TK2; human.
DR GenomeRNAi; 7084; -.
DR Pharos; O00142; Tchem.
DR PRO; PR:O00142; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O00142; protein.
DR Bgee; ENSG00000166548; Expressed in calcaneal tendon and 196 other tissues.
DR ExpressionAtlas; O00142; baseline and differential.
DR Genevisible; O00142; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004137; F:deoxycytidine kinase activity; IDA:UniProtKB.
DR GO; GO:0019136; F:deoxynucleoside kinase activity; IBA:GO_Central.
DR GO; GO:0019206; F:nucleoside kinase activity; TAS:Reactome.
DR GO; GO:0004797; F:thymidine kinase activity; IDA:UniProtKB.
DR GO; GO:0046092; P:deoxycytidine metabolic process; IEA:Ensembl.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0043097; P:pyrimidine nucleoside salvage; TAS:Reactome.
DR GO; GO:0046104; P:thymidine metabolic process; IEA:Ensembl.
DR CDD; cd01673; dNK; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR002624; DCK/DGK.
DR InterPro; IPR031314; DNK_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01712; dNK; 1.
DR PIRSF; PIRSF000705; DNK; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Direct protein sequencing;
KW Disease variant; DNA synthesis; Kinase; Mitochondrion; Nucleotide-binding;
KW Primary mitochondrial disease; Progressive external ophthalmoplegia;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..33
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:9989599"
FT CHAIN 34..265
FT /note="Thymidine kinase 2, mitochondrial"
FT /id="PRO_0000016842"
FT REGION 20..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 133
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O57203"
FT BINDING 57..65
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O57203"
FT VAR_SEQ 1..97
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054606"
FT VAR_SEQ 1..41
FT /note="MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPP -> MGAFCQR
FT PSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9079672"
FT /id="VSP_003028"
FT VAR_SEQ 1
FT /note="M -> MRPGLFKGQAPGSRRRPTAGLAVVRADSHKKEPRASGSARPAM (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:20843780"
FT /id="VSP_058694"
FT VAR_SEQ 53..77
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043503"
FT VAR_SEQ 78..95
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044459"
FT VARIANT 53
FT /note="I -> M (in MTDPS2; dbSNP:rs137854432)"
FT /evidence="ECO:0000269|PubMed:12391347"
FT /id="VAR_019419"
FT VARIANT 64
FT /note="T -> M (in MTDPS2; dbSNP:rs281865487)"
FT /evidence="ECO:0000269|PubMed:15907288"
FT /id="VAR_023790"
FT VARIANT 108
FT /note="T -> M (in MTDPS2; reduction of activity;
FT dbSNP:rs137854431)"
FT /evidence="ECO:0000269|PubMed:12391347,
FT ECO:0000269|PubMed:15639197"
FT /id="VAR_019420"
FT VARIANT 117
FT /note="M -> V (in MTDPS2; severe form of combined brain and
FT muscular atrophy; depletion of mtDNA in skeletal muscle;
FT normal residual mtDNA in blood and fibroblasts)"
FT /evidence="ECO:0000269|PubMed:25446393"
FT /id="VAR_072789"
FT VARIANT 121
FT /note="H -> N (in MTDPS2; reduction of activity in muscles;
FT dbSNP:rs137854429)"
FT /evidence="ECO:0000269|PubMed:11687801,
FT ECO:0000269|PubMed:12391347"
FT /id="VAR_019421"
FT VARIANT 139
FT /note="A -> V (in MTDPS2; severe form of combined brain and
FT muscular atrophy; depletion of mtDNA in skeletal muscle;
FT normal residual mtDNA in blood and fibroblasts;
FT dbSNP:rs281865494)"
FT /evidence="ECO:0000269|PubMed:25446393"
FT /id="VAR_072790"
FT VARIANT 183
FT /note="R -> W (in MTDPS2 and PEOB3; reduction of activity;
FT reduced affinity for ATP; dbSNP:rs137886900)"
FT /evidence="ECO:0000269|PubMed:15907288,
FT ECO:0000269|PubMed:21937588"
FT /id="VAR_023791"
FT VARIANT 188
FT /note="T -> A (in PEOB3; reduction of activity; reduced
FT affinity for ATP; dbSNP:rs281865495)"
FT /evidence="ECO:0000269|PubMed:21937588"
FT /id="VAR_076984"
FT VARIANT 192
FT /note="R -> K (in MTDPS2; reduction of activity;
FT dbSNP:rs281865496)"
FT /evidence="ECO:0000269|PubMed:15639197"
FT /id="VAR_023792"
FT VARIANT 212
FT /note="I -> N (in MTDPS2; reduction of activity in muscles;
FT dbSNP:rs137854430)"
FT /evidence="ECO:0000269|PubMed:11687801"
FT /id="VAR_019422"
FT CONFLICT 37
FT /note="R -> Y (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 49
FT /note="K -> E (in Ref. 5; BAG57808)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="S -> G (in Ref. 1; AAC51167)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="L -> P (in Ref. 5; BAG57808)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="D -> DH (in Ref. 2; CAA71523)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="Missing (in Ref. 1; AAC51167)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="N -> S (in Ref. 5; BAG57808)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 265 AA; 31005 MW; 1E9CB62D0321A992 CRC64;
MLLWPLRGWA ARALRCFGPG SRGSPASGPG PRRVQRRAWP PDKEQEKEKK SVICVEGNIA
SGKTTCLEFF SNATDVEVLT EPVSKWRNVR GHNPLGLMYH DASRWGLTLQ TYVQLTMLDR
HTRPQVSSVR LMERSIHSAR YIFVENLYRS GKMPEVDYVV LSEWFDWILR NMDVSVDLIV
YLRTNPETCY QRLKKRCREE EKVIPLEYLE AIHHLHEEWL IKGSLFPMAA PVLVIEADHH
MERMLELFEQ NRDRILTPEN RKHCP
