TK2

Protein identityUniProt · HPA

UniProt accession

O00142

Gene

TK2

Ensembl

ENSG00000166548

Chromosome

16

Canonical length

265 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

OverviewNCBI Gene

This gene encodes a deoxyribonucleoside kinase that specifically phosphorylates thymidine, deoxycytidine, and deoxyuridine. The encoded enzyme localizes to the mitochondria and is required for mitochondrial DNA synthesis. Mutations in this gene are associated with a myopathic form of mitochondrial DNA depletion syndrome. Alternate splicing results in multiple transcript variants encoding distinct isoforms, some of which lack transit peptide, so are not localized to mitochondria. [provided by RefSeq, Dec 2012]

Canonical amino-acid sequenceUniProt

265 residues, UniProt reviewed canonical sequence.

>O00142|TK2
     1  MLLWPLRGWA ARALRCFGPG SRGSPASGPG PRRVQRRAWP PDKEQEKEKK SVICVEGNIA
    61  SGKTTCLEFF SNATDVEVLT EPVSKWRNVR GHNPLGLMYH DASRWGLTLQ TYVQLTMLDR
   121  HTRPQVSSVR LMERSIHSAR YIFVENLYRS GKMPEVDYVV LSEWFDWILR NMDVSVDLIV
   181  YLRTNPETCY QRLKKRCREE EKVIPLEYLE AIHHLHEEWL IKGSLFPMAA PVLVIEADHH
   241  MERMLELFEQ NRDRILTPEN RKHCP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TK2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

45 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TK2.

Disease | AllUniProt

Conditions TK2 is implicated in, by any mechanism.

• Mitochondrial DNA depletion syndrome 2 (MTDPS2) MIM:609560
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3 (PEOB3) MIM:617069

Disease | GeneticClinVar

95 pathogenic / likely-pathogenic of 634 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial disease
• Mitochondrial DNA depletion syndrome, myopathic form
• Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 3
• Mitochondrial DNA depletion syndrome
• TK2-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.19

gnomAD pLI

0

gnomAD missense Z

0.15

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA biosynthetic process
• nucleobase-containing compound metabolic process
• pyrimidine nucleoside salvage
• thymidine metabolic process
• deoxycytidine metabolic process

Molecular functions

• ATP binding
• deoxycytidine kinase activity
• thymidine kinase activity
• deoxynucleoside kinase activity
• nucleoside kinase activity

Cellular components

• cytoplasm
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Deoxynucleoside kinase
• P-loop containing nucleoside triphosphate hydrolase
• Deoxynucleoside kinase domain
• Deoxyribonucleoside Kinase
• Deoxynucleoside kinase

KeywordsUniProt

• ATP-binding
• DNA synthesis
• Kinase
• Mitochondrion
• Nucleotide-binding
• Primary mitochondrial disease
• Progressive external ophthalmoplegia
• Transferase
• Transit peptide