Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS1V4XB)

• DOT Name: Thymidine kinase 2, mitochondrial (TK2)
• Synonyms: EC 2.7.1.21; 2'-deoxyuridine kinase TK2; EC 2.7.1.74; Deoxycytidine kinase TK2; EC 2.7.1.-; Mt-TK
• Gene Name: TK2
• Related Disease:
  Mitochondrial disease
  Mitochondrial DNA depletion syndrome, myopathic form
  Coenzyme Q10 deficiency
  Dentatorubral-pallidoluysian atrophy
  Dilated cardiomyopathy 1A
  Gastrointestinal stromal tumour
  Germ cell tumor
  Hereditary cerebellar ataxia
  Herpes simplex infection
  Leber hereditary optic neuropathy
  Liver failure
  Mitochondrial DNA depletion syndrome
  Mitochondrial encephalomyopathy
  Myelodysplastic syndrome
  Myopathy
  Progressive external ophthalmoplegia
  Ptosis
  Spinal muscular atrophy
  Spinal muscular atrophy, type III
  Spinocerebellar ataxia type 3
  Spinocerebellar ataxia type 6
  Crouzon syndrome
  Fragile X-associated tremor/ataxia syndrome
  Huntington disease-like 2
  Myotonic dystrophy type 2
  Respiratory failure
  Sensorineural hearing loss disorder
  Spinocerebellar ataxia type 10
  Autosomal recessive progressive external ophthalmoplegia
  Epilepsy
  Mitochondrial myopathy
  Sickle-cell anaemia
  Skeletal muscle disorder
  Systemic primary carnitine deficiency disease
• UniProt ID: KITM_HUMAN
• EC Number: 2.7.1.-; 2.7.1.21; 2.7.1.74
• Pfam ID: PF01712
• Sequence:
  MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPPDKEQEKEKKSVICVEGNIA
  SGKTTCLEFFSNATDVEVLTEPVSKWRNVRGHNPLGLMYHDASRWGLTLQTYVQLTMLDR
  HTRPQVSSVRLMERSIHSARYIFVENLYRSGKMPEVDYVVLSEWFDWILRNMDVSVDLIV
  YLRTNPETCYQRLKKRCREEEKVIPLEYLEAIHHLHEEWLIKGSLFPMAAPVLVIEADHH
  MERMLELFEQNRDRILTPENRKHCP
• Function: Phosphorylates thymidine, deoxycytidine, and deoxyuridine in the mitochondrial matrix. In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on TK2 and DGUOK. Widely used as target of antiviral and chemotherapeutic agents.
• Tissue Specificity: Predominantly expressed in liver, pancreas, muscle, and brain.
• KEGG Pathway:
  Pyrimidine metabolism (hsa00240)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway: Pyrimidine salvage (R-HSA-73614)
• BioCyc Pathway: MetaCyc:HS09420-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[1]
Mitochondrial DNA depletion syndrome, myopathic form	DIS9CBUI	Definitive	Autosomal recessive	[2]
Coenzyme Q10 deficiency	DIS1HGDF	Strong	Genetic Variation	[3]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Strong	Genetic Variation	[4]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[5]
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Genetic Variation	[6]
Germ cell tumor	DIS62070	Strong	Genetic Variation	[6]
Hereditary cerebellar ataxia	DIS17A1W	Strong	Genetic Variation	[4]
Herpes simplex infection	DISL1SAV	Strong	Genetic Variation	[7]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Genetic Variation	[8]
Liver failure	DISLGEL6	Strong	Genetic Variation	[9]
Mitochondrial DNA depletion syndrome	DISIGZSM	Strong	Genetic Variation	[10]
Mitochondrial encephalomyopathy	DISA6PTN	Strong	Genetic Variation	[11]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[12]
Myopathy	DISOWG27	Strong	Biomarker	[13]
Progressive external ophthalmoplegia	DISX4ATI	Strong	Genetic Variation	[14]
Ptosis	DISJZNIY	Strong	Genetic Variation	[15]
Spinal muscular atrophy	DISTLKOB	Strong	Genetic Variation	[16]
Spinal muscular atrophy, type III	DISNG3SD	Strong	Genetic Variation	[17]
Spinocerebellar ataxia type 3	DISQBQID	Strong	Biomarker	[18]
Spinocerebellar ataxia type 6	DISH7224	Strong	Genetic Variation	[18]
Crouzon syndrome	DISIAVZU	moderate	Genetic Variation	[19]
Fragile X-associated tremor/ataxia syndrome	DISKB25R	moderate	Biomarker	[20]
Huntington disease-like 2	DISM3G09	moderate	Genetic Variation	[20]
Myotonic dystrophy type 2	DIS5ZWF1	moderate	Genetic Variation	[20]
Respiratory failure	DISVMYJO	moderate	Genetic Variation	[21]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[22]
Spinocerebellar ataxia type 10	DISEJVJK	moderate	Genetic Variation	[20]
Autosomal recessive progressive external ophthalmoplegia	DISY53WH	Supportive	Autosomal recessive	[14]
Epilepsy	DISBB28L	Disputed	Genetic Variation	[23]
Mitochondrial myopathy	DIS9SA7V	Limited	Genetic Variation	[24]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[18]
Skeletal muscle disorder	DISR9DGU	Limited	Biomarker	[25]
Systemic primary carnitine deficiency disease	DIS9OPZ4	Limited	Biomarker	[18]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fialuridine	DMCIGRB	Phase 2	Thymidine kinase 2, mitochondrial (TK2) affects the response to substance of Fialuridine.	[41]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[26]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[27]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[28]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Thymidine kinase 2, mitochondrial (TK2).	[30]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Thymidine kinase 2, mitochondrial (TK2).	[31]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Thymidine kinase 2, mitochondrial (TK2).	[32]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[33]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[34]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Thymidine kinase 2, mitochondrial (TK2).	[31]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Thymidine kinase 2, mitochondrial (TK2).	[35]
Zalcitabine	DMH7MUV	Approved	Zalcitabine decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[39]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Thymidine kinase 2, mitochondrial (TK2).	[40]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Thymidine kinase 2, mitochondrial (TK2).	[38]

References

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