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O00142 (KITM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thymidine kinase 2, mitochondrial

EC=2.7.1.21
Alternative name(s):
Mt-TK
Gene names
Name:TK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length265 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processDNA synthesis
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainTransit peptide
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processdeoxycytidine metabolic process

Inferred from electronic annotation. Source: Ensembl

deoxyribonucleoside monophosphate biosynthetic process

Traceable author statement Ref.1. Source: GOC

deoxyribonucleotide metabolic process

Inferred from electronic annotation. Source: Ensembl

mitochondrial DNA replication

Inferred from electronic annotation. Source: Ensembl

nucleobase-containing compound metabolic process

Traceable author statement Ref.1. Source: ProtInc

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleobase metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleoside salvage

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

thymidine metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentmitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

deoxycytidine kinase activity

Inferred from electronic annotation. Source: Ensembl

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 5 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.
Isoform 5 (identifier: O00142-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-97: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3333Mitochondrion Ref.2
Chain34 – 265232Thymidine kinase 2, mitochondrial
PRO_0000016842

Regions

Nucleotide binding57 – 659ATP By similarity

Sites

Active site1331Proton acceptor Potential
Binding site811Substrate By similarity
Binding site991Substrate By similarity
Binding site1101Substrate By similarity
Binding site1341Substrate By similarity
Binding site2011Substrate By similarity

Natural variations

Alternative sequence1 – 9797Missing in isoform 5.
VSP_054606
Alternative sequence1 – 4141MLLWP…RAWPP → MGAFCQRPSS in isoform Short.
VSP_003028
Alternative sequence53 – 7725Missing in isoform 3.
VSP_043503
Alternative sequence78 – 9518Missing in isoform 4.
VSP_044459
Natural variant531I → M in MTDPS2. Ref.8
VAR_019419
Natural variant641T → M in MTDPS2. Ref.10
VAR_023790
Natural variant1081T → M in MTDPS2; reduction of activity. Ref.8 Ref.9
VAR_019420
Natural variant1211H → N in MTDPS2. Ref.7 Ref.8
VAR_019421
Natural variant1831R → W in MTDPS2. Ref.10
VAR_023791
Natural variant1921R → K in MTDPS2; reduction of activity. Ref.9
VAR_023792
Natural variant2121I → N in MTDPS2. Ref.7
VAR_019422

Experimental info

Sequence conflict371R → Y AA sequence Ref.2
Sequence conflict491K → E in BAG57808. Ref.4
Sequence conflict611S → G in AAC51167. Ref.1
Sequence conflict2061L → P in BAG57808. Ref.4
Sequence conflict2381D → DH in CAA71523. Ref.2
Sequence conflict2411Missing in AAC51167. Ref.1
Sequence conflict2511N → S in BAG57808. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified July 28, 2009. Version 4.
Checksum: 1E9CB62D0321A992

FASTA26531,005
        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 

« Hide

Isoform Short [UniParc].

Checksum: BA62F86B35942E34
Show »

FASTA23427,562
Isoform 3 [UniParc].

Checksum: 5BBDA88F49F0F331
Show »

FASTA24028,374
Isoform 4 [UniParc].

Checksum: 9EB1F18D680A66BB
Show »

FASTA24728,920
Isoform 5 [UniParc].

Checksum: 436EAB164C5784EE
Show »

FASTA16820,281

References

« Hide '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. expand/collapse author list , 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; 4 AND 5).
Tissue: Brain and Testis.
[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. expand/collapse author list , 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. expand/collapse author list , 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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U77088 mRNA. Translation: AAC51167.1.
Y10498 mRNA. Translation: CAA71523.3.
AK294627 mRNA. Translation: BAG57808.1.
AK302976 mRNA. Translation: BAG64119.1.
AK316226 mRNA. Translation: BAH14597.1.
AC010542 Genomic DNA. No translation available.
CH471092 Genomic DNA. Translation: EAW83013.1.
CH471092 Genomic DNA. Translation: EAW83015.1.
CCDSCCDS10805.2. [O00142-1]
CCDS54016.1. [O00142-3]
CCDS54017.1. [O00142-4]
CCDS54018.1. [O00142-2]
RefSeqNP_001166114.1. NM_001172643.1. [O00142-2]
NP_001166115.1. NM_001172644.1. [O00142-3]
NP_001258864.1. NM_001271935.1.
NP_001258979.1. NM_001272050.1. [O00142-5]
NP_004605.4. NM_004614.4. [O00142-1]
UniGeneHs.512619.

3D structure databases

ProteinModelPortalO00142.
SMRO00142. Positions 53-221.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000299697.

Chemistry

BindingDBO00142.
ChEMBLCHEMBL4580.

PTM databases

PhosphoSiteO00142.

Proteomic databases

MaxQBO00142.
PaxDbO00142.
PRIDEO00142.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000417693; ENSP00000407469; ENSG00000166548. [O00142-4]
ENST00000451102; ENSP00000414334; ENSG00000166548. [O00142-1]
ENST00000525974; ENSP00000434594; ENSG00000166548.
ENST00000527284; ENSP00000435312; ENSG00000166548. [O00142-2]
ENST00000545043; ENSP00000438143; ENSG00000166548. [O00142-3]
GeneID7084.
KEGGhsa:7084.
UCSCuc002eor.3. human. [O00142-2]
uc002eos.3. human. [O00142-1]
uc010viq.2. human. [O00142-4]
uc010vir.2. human. [O00142-3]

Organism-specific databases

CTD7084.
GeneCardsGC16M066542.
GeneReviewsTK2.
H-InvDBHIX0021286.
HGNCHGNC:11831. TK2.
HPAHPA041162.
MIM188250. gene.
609560. phenotype.
neXtProtNX_O00142.
Orphanet254886. Autosomal recessive progressive external ophthalmoplegia.
254875. Mitochondrial DNA depletion syndrome, myopathic form.
PharmGKBPA36535.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1428.
HOVERGENHBG006216.
InParanoidO00142.
KOK00857.
PhylomeDBO00142.
TreeFamTF324413.

Enzyme and pathway databases

BioCycMetaCyc:HS09420-MONOMER.
BRENDA2.7.1.21. 2681.
ReactomeREACT_111217. Metabolism.
REACT_115566. Cell Cycle.
SABIO-RKO00142.

Gene expression databases

ArrayExpressO00142.
BgeeO00142.
CleanExHS_TK2.
GenevestigatorO00142.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR002624. Deoxynucleoside_kinase.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10513. PTHR10513. 1 hit.
PfamPF01712. dNK. 1 hit.
[Graphical view]
PIRSFPIRSF000705. DNK. 1 hit.
SUPFAMSSF52540. SSF52540. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi7084.
NextBio27709.
PROO00142.
SOURCESearch...

Entry information

Entry nameKITM_HUMAN
AccessionPrimary (citable) accession number: O00142
Secondary accession number(s): B4DGJ7 expand/collapse secondary AC list , B4DZK7, B7ZAB1, E9PH08, O15238
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 28, 2009
Last modified: July 9, 2014
This is version 135 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM