Reviewed, UniProtKB/Swiss-Prot O00142 (KITM_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in TK2 are a cause of myopathic mitochondrial DNA depletion syndrome (MDS) [MIM:609560]. MDS is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA (mtDNA) copy number. Primary mtDNA depletion is inherited as an autosomal recessive trait and may affect single organs, typically muscle or liver, or multiple tissues. The myopathic form of mtDNA depletion syndrome is a slowly progressive mitochondrial disorder starting in childhood and associated with less severe depletion of mtDNA in skeletal muscle (66 to 86%) compared to the hepatocerebral form of mtDNA depletion syndrome which shows up to 99% mtDNA depletion in liver. Ref.5 Ref.6 Ref.7 Ref.8
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
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW thymidine kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 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.

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 – 64	8	ATP Potential
Natural variations
	Alternative sequence	1 – 41	41	MLLWP…RAWPP → MGAFCQRPSS in isoform Short.		VSP_003028
	Natural variant	53	1	I → M in MDS. Ref.6		VAR_019419
	Natural variant	64	1	T → M in MDS. Ref.8		VAR_023790
	Natural variant	108	1	T → M in MDS; reduction of activity. Ref.6 Ref.7		VAR_019420
	Natural variant	121	1	H → N in MDS. Ref.5 Ref.6		VAR_019421
	Natural variant	183	1	R → W in MDS. Ref.8		VAR_023791
	Natural variant	192	1	R → K in MDS; reduction of activity. Ref.7		VAR_023792
	Natural variant	212	1	I → N in MDS. Ref.5		VAR_019422
Experimental info
	Sequence conflict	37	1	R → Y AA sequence Ref.2
	Sequence conflict	61	1	S → G in AAC51167. Ref.1
	Sequence conflict	238	1	D → DH in CAA71523. Ref.2
	Sequence conflict	241	1	Missing in AAC51167. Ref.1

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. 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

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: 9079672] [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: 9989599] [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]	"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: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 11687801] [Abstract] Cited for: VARIANTS MDS ASN-121 AND ASN-212.
[6]	"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: 12391347] [Abstract] Cited for: VARIANTS MDS MET-53; MET-108 AND ASN-121.
[7]	"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: 15639197] [Abstract] Cited for: VARIANTS MDS MET-108 AND LYS-192, CHARACTERIZATION OF VARIANTS MDS MET-108 AND LYS-192.
[8]	"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: 15907288] [Abstract] Cited for: VARIANTS MDS MET-64 AND TRP-183.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U77088 mRNA. Translation: AAC51167.1. Y10498 mRNA. Translation: CAA71523.3. AC010542 Genomic DNA. No translation available.
IPI	IPI00215650. IPI00337439.
UniGene	Hs.512619
3D structure databases
HSSP	HSSP built from PDB template 1OT3 based on UniProtKB Q9XZT6.
ModBase	Search...
Protein-protein interaction databases
STRING	O00142.
Proteomic databases
PRIDE	O00142.
Genome annotation databases
Ensembl	ENST00000299697; ENSP00000299697; ENSG00000166548; Homo sapiens. [Genome view] ENST00000417693; ENSP00000407469; ENSG00000166548; Homo sapiens. [Genome view] ENST00000451102; ENSP00000414334; ENSG00000166548; Homo sapiens. [Genome view]
Organism-specific databases
GeneCards	GC16M065102.
H-InvDB	HIX0013113. HIX0021286.
HGNC	HGNC:11831. TK2.
MIM	188250. gene. 609560. phenotype.
Orphanet	35698. Mitochondrial DNA depletion syndrome.
PharmGKB	PA134884391.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O00142.
Enzyme and pathway databases
BRENDA	2.7.1.21. 247.
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_1698. Metablism of nucleotides.
Gene expression databases
ArrayExpress	O00142.
Bgee	O00142.
CleanEx	HS_TK2.
Genevestigator	O00142.
GermOnline	ENSG00000166548. Homo sapiens.
Family and domain databases
PANTHER	PTHR10513. dNK. 1 hit.
Pfam	PF01712. dNK. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

KITM_HUMAN

Accession

Primary (citable) accession number: O00142
Secondary accession number(s): O15238

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 28, 2009
Last modified:	November 3, 2009
This is version 87 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.