O00142 (KITM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidine kinase 2, mitochondrial
EC=2.7.1.21

Alternative name(s):
Mt-TK

Gene names

Name:

TK2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	265 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Deoxyribonucleoside kinase that phosphorylates thymidine, deoxycytidine, and deoxyuridine. Also phosphorylates anti-viral and anti-cancer nucleoside analogs.
Catalytic activity	ATP + thymidine = ADP + thymidine 5'-phosphate.
Subunit structure	Monomer.
Subcellular location	Mitochondrion.
Tissue specificity	Predominantly expressed in liver, pancreas, muscle, and brain.
Involvement in disease	Mitochondrial DNA depletion syndrome 2 (MTDPS2) [MIM:609560]: A disorder due to mitochondrial dysfunction characterized by childhood onset of muscle weakness associated with depletion of mtDNA in skeletal muscle. There is wide clinical variability; some patients have onset in infancy and show a rapidly progressive course with early death due to respiratory failure, whereas others have later onset of a slowly progressive myopathy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.10
Sequence similarities	Belongs to the DCK/DGK family.

Ontologies

Keywords
Biological process	DNA synthesis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	deoxycytidine metabolic process Inferred from electronic annotation. Source: Compara deoxyribonucleotide metabolic process Inferred from electronic annotation. Source: Compara mitochondrial DNA replication Inferred from electronic annotation. Source: Compara pyrimidine nucleobase metabolic process Traceable author statement. Source: Reactome pyrimidine nucleoside salvage Traceable author statement. Source: Reactome thymidine metabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW deoxycytidine kinase activity Inferred from electronic annotation. Source: Compara phosphotransferase activity, alcohol group as acceptor Inferred from electronic annotation. Source: InterPro thymidine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: O00142-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Short (identifier: O00142-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-41: MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPP → MGAFCQRPSS

Note: No experimental confirmation available.

Isoform 3 (identifier: O00142-3)

The sequence of this isoform differs from the canonical sequence as follows:
     53-77: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: O00142-4)

The sequence of this isoform differs from the canonical sequence as follows:
     78-95: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 33	33	Mitochondrion Ref.2
	Chain	34 – 265	232	Thymidine kinase 2, mitochondrial		PRO_0000016842
Regions
	Nucleotide binding	57 – 65	9	ATP By similarity
Sites
	Active site	133	1	Proton acceptor Potential
	Binding site	81	1	Substrate By similarity
	Binding site	99	1	Substrate By similarity
	Binding site	110	1	Substrate By similarity
	Binding site	134	1	Substrate By similarity
	Binding site	201	1	Substrate By similarity
Natural variations
	Alternative sequence	1 – 41	41	MLLWP…RAWPP → MGAFCQRPSS in isoform Short.		VSP_003028
	Alternative sequence	53 – 77	25	Missing in isoform 3.		VSP_043503
	Alternative sequence	78 – 95	18	Missing in isoform 4.		VSP_044459
	Natural variant	53	1	I → M in MTDPS2. Ref.8		VAR_019419
	Natural variant	64	1	T → M in MTDPS2. Ref.10		VAR_023790
	Natural variant	108	1	T → M in MTDPS2; reduction of activity. Ref.8 Ref.9		VAR_019420
	Natural variant	121	1	H → N in MTDPS2. Ref.7 Ref.8		VAR_019421
	Natural variant	183	1	R → W in MTDPS2. Ref.10		VAR_023791
	Natural variant	192	1	R → K in MTDPS2; reduction of activity. Ref.9		VAR_023792
	Natural variant	212	1	I → N in MTDPS2. Ref.7		VAR_019422
Experimental info
	Sequence conflict	37	1	R → Y AA sequence Ref.2
	Sequence conflict	49	1	K → E in BAG57808. Ref.4
	Sequence conflict	61	1	S → G in AAC51167. Ref.1
	Sequence conflict	206	1	L → P in BAG57808. Ref.4
	Sequence conflict	238	1	D → DH in CAA71523. Ref.2
	Sequence conflict	241	1	Missing in AAC51167. Ref.1
	Sequence conflict	251	1	N → S in BAG57808. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified July 28, 2009. Version 4. Checksum: 1E9CB62D0321A992	FASTA	265	31,005
	10 20 30 40 50 60 MLLWPLRGWA ARALRCFGPG SRGSPASGPG PRRVQRRAWP PDKEQEKEKK SVICVEGNIA 70 80 90 100 110 120 SGKTTCLEFF SNATDVEVLT EPVSKWRNVR GHNPLGLMYH DASRWGLTLQ TYVQLTMLDR 130 140 150 160 170 180 HTRPQVSSVR LMERSIHSAR YIFVENLYRS GKMPEVDYVV LSEWFDWILR NMDVSVDLIV 190 200 210 220 230 240 YLRTNPETCY QRLKKRCREE EKVIPLEYLE AIHHLHEEWL IKGSLFPMAA PVLVIEADHH 250 260 MERMLELFEQ NRDRILTPEN RKHCP
	Isoform Short [UniParc]. Checksum: BA62F86B35942E34	FASTA	234	27,562
	10 20 30 40 50 60 MGAFCQRPSS DKEQEKEKKS VICVEGNIAS GKTTCLEFFS NATDVEVLTE PVSKWRNVRG 70 80 90 100 110 120 HNPLGLMYHD ASRWGLTLQT YVQLTMLDRH TRPQVSSVRL MERSIHSARY IFVENLYRSG 130 140 150 160 170 180 KMPEVDYVVL SEWFDWILRN MDVSVDLIVY LRTNPETCYQ RLKKRCREEE KVIPLEYLEA 190 200 210 220 230 IHHLHEEWLI KGSLFPMAAP VLVIEADHHM ERMLELFEQN RDRILTPENR KHCP
	Isoform 3 [UniParc]. Checksum: 5BBDA88F49F0F331	FASTA	240	28,374
	10 20 30 40 50 60 MLLWPLRGWA ARALRCFGPG SRGSPASGPG PRRVQRRAWP PDKEQEKEKK SVVLTEPVSK 70 80 90 100 110 120 WRNVRGHNPL GLMYHDASRW GLTLQTYVQL TMLDRHTRPQ VSSVRLMERS IHSARYIFVE 130 140 150 160 170 180 NLYRSGKMPE VDYVVLSEWF DWILRNMDVS VDLIVYLRTN PETCYQRLKK RCREEEKVIP 190 200 210 220 230 240 LEYLEAIHHL HEEWLIKGSL FPMAAPVLVI EADHHMERML ELFEQNRDRI LTPENRKHCP
	Isoform 4 [UniParc]. Checksum: 9EB1F18D680A66BB	FASTA	247	28,920
	10 20 30 40 50 60 MLLWPLRGWA ARALRCFGPG SRGSPASGPG PRRVQRRAWP PDKEQEKEKK SVICVEGNIA 70 80 90 100 110 120 SGKTTCLEFF SNATDVEGLM YHDASRWGLT LQTYVQLTML DRHTRPQVSS VRLMERSIHS 130 140 150 160 170 180 ARYIFVENLY RSGKMPEVDY VVLSEWFDWI LRNMDVSVDL IVYLRTNPET CYQRLKKRCR 190 200 210 220 230 240 EEEKVIPLEY LEAIHHLHEE WLIKGSLFPM AAPVLVIEAD HHMERMLELF EQNRDRILTP ENRKHCP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA and chromosome localization of the gene for human thymidine kinase 2." Johansson M., Karlsson A. J. Biol. Chem. 272:8454-8458(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Tissue: Liver.
[2]	"Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates." Wang L., Munch-Petersen B., Herrstroem Sjoeberg A., Hellman U., Bergman T., Joernvall H., Eriksson S. FEBS Lett. 443:170-174(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), PROTEIN SEQUENCE OF 34-61 (ISOFORM LONG), CHARACTERIZATION. Tissue: Brain.
[3]	Wang L. Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). Tissue: Brain.
[5]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy." Saada A., Shaag A., Mandel H., Nevo Y., Eriksson S., Elpeleg O. Nat. Genet. 29:342-344(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MTDPS2 ASN-121 AND ASN-212.
[8]	"Mitochondrial DNA depletion: mutations in thymidine kinase gene with myopathy and SMA." Mancuso M., Salviati L., Sacconi S., Otaegui D., Camano P., Marina A., Bacman S., Moraes C.T., Carlo J.R., Garcia M., Garcia-Alvarez M., Monzon L., Naini A.B., Hirano M., Bonilla E., Taratuto A.L., DiMauro S., Vu T.H. Neurology 59:1197-1202(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MTDPS2 MET-53; MET-108 AND ASN-121.
[9]	"Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes." Wang L., Limongelli A., Vila M.R., Carrara F., Zeviani M., Eriksson S. Mol. Genet. Metab. 84:75-82(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MTDPS2 MET-108 AND LYS-192, CHARACTERIZATION OF VARIANTS MTDPS2 MET-108 AND LYS-192.
[10]	"Novel mutations in the thymidine kinase 2 gene (TK2) associated with fatal mitochondrial myopathy and mitochondrial DNA depletion." Tulinius M., Moslemi A.-R., Darin N., Holme E., Oldfors A. Neuromuscul. Disord. 15:412-415(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MTDPS2 MET-64 AND TRP-183.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U77088 mRNA. Translation: AAC51167.1. Y10498 mRNA. Translation: CAA71523.3. AK294627 mRNA. Translation: BAG57808.1. AK316226 mRNA. Translation: BAH14597.1. AC010542 Genomic DNA. No translation available. CH471092 Genomic DNA. Translation: EAW83015.1.
IPI	IPI00215650. IPI00337439. IPI00939299. IPI00955983.
RefSeq	NP_001166114.1. NM_001172643.1. NP_001166115.1. NM_001172644.1. NP_001258864.1. NM_001271935.1. NP_004605.4. NM_004614.4.
UniGene	Hs.512619.
3D structure databases
ProteinModelPortal	O00142.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000299697.
PTM databases
PhosphoSite	O00142.
Proteomic databases
PaxDb	O00142.
PRIDE	O00142.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000417693; ENSP00000407469; ENSG00000166548. ENST00000451102; ENSP00000414334; ENSG00000166548. ENST00000527284; ENSP00000435312; ENSG00000166548. ENST00000545043; ENSP00000438143; ENSG00000166548.
GeneID	7084.
KEGG	hsa:7084.
UCSC	uc002eor.3. human. uc002eos.3. human.
Organism-specific databases
CTD	7084.
GeneCards	GC16M066506.
H-InvDB	HIX0021286.
HGNC	HGNC:11831. TK2.
HPA	HPA041162.
MIM	188250. gene. 609560. phenotype.
neXtProt	NX_O00142.
Orphanet	254886. Autosomal recessive progressive external ophthalmoplegia. 254875. Mitochondrial DNA depletion syndrome, myopathic form.
PharmGKB	PA36535.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1428.
HOVERGEN	HBG006216.
InParanoid	O00142.
KO	K00857.
OrthoDB	EOG4B8JF5.
Enzyme and pathway databases
BRENDA	2.7.1.21. 2681.
Reactome	REACT_111217. Metabolism. REACT_115566. Cell Cycle.
SABIO-RK	O00142.
Gene expression databases
ArrayExpress	O00142.
Bgee	O00142.
CleanEx	HS_TK2.
Genevestigator	O00142.
GermOnline	ENSG00000166548. Homo sapiens.
Family and domain databases
InterPro	IPR002624. Deoxynucleoside_kinase. [Graphical view]
PANTHER	PTHR10513. PTHR10513. 1 hit.
Pfam	PF01712. dNK. 1 hit. [Graphical view]
PIRSF	PIRSF000705. DNK. 1 hit.
ProtoNet	Search...
Other
BindingDB	O00142.
ChEMBL	CHEMBL4580.
GenomeRNAi	7084.
NextBio	27709.
SOURCE	Search...

Entry information

Entry name

KITM_HUMAN

Accession

Primary (citable) accession number: O00142
Secondary accession number(s): B4DGJ7 , B7ZAB1, E9PH08, O15238

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 28, 2009
Last modified:	May 1, 2013
This is version 122 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.