TISIDB

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Mitochondrion.
Domain	PF01712 Deoxynucleoside kinase
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.

> Gene Ontology [ TOP ]
Biological Process	GO:0006213 pyrimidine nucleoside metabolic process GO:0008655 pyrimidine-containing compound salvage GO:0009116 nucleoside metabolic process GO:0009120 deoxyribonucleoside metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0009124 nucleoside monophosphate biosynthetic process GO:0009157 deoxyribonucleoside monophosphate biosynthetic process GO:0009162 deoxyribonucleoside monophosphate metabolic process GO:0009163 nucleoside biosynthetic process GO:0009165 nucleotide biosynthetic process GO:0043094 cellular metabolic compound salvage GO:0043097 pyrimidine nucleoside salvage GO:0043174 nucleoside salvage GO:0046092 deoxycytidine metabolic process GO:0046104 thymidine metabolic process GO:0046125 pyrimidine deoxyribonucleoside metabolic process GO:0046134 pyrimidine nucleoside biosynthetic process GO:0071897 DNA biosynthetic process GO:0072527 pyrimidine-containing compound metabolic process GO:0072528 pyrimidine-containing compound biosynthetic process GO:1901293 nucleoside phosphate biosynthetic process GO:1901657 glycosyl compound metabolic process GO:1901659 glycosyl compound biosynthetic process
Molecular Function	GO:0004137 deoxycytidine kinase activity GO:0004797 thymidine kinase activity GO:0019136 deoxynucleoside kinase activity GO:0019205 nucleobase-containing compound kinase activity GO:0019206 nucleoside kinase activity
Cellular Component	GO:0005759 mitochondrial matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00240 Pyrimidine metabolism hsa00983 Drug metabolism - other enzymes hsa01100 Metabolic pathways
Reactome	R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-113510: E2F mediated regulation of DNA replication R-HSA-69206: G1/S Transition R-HSA-69205: G1/S-Specific Transcription R-HSA-1430728: Metabolism R-HSA-15869: Metabolism of nucleotides R-HSA-453279: Mitotic G1-G1/S phases R-HSA-73848: Pyrimidine metabolism R-HSA-73614: Pyrimidine salvage reactions

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TK2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of TK2 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: -2.73; FDR: 0.04630	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of TK2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.308	0.206
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.73	0.631
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.007	0.995
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.103	0.698
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.351	0.83
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.207	0.924
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.289	0.41
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.195	0.894
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.405	0.804
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.482	0.732
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.05	0.617
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.194	0.011

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TK2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TK2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TK2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TK2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TK2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TK2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TK2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TK2
Name	thymidine kinase 2, mitochondrial
Aliases	MTDPS2
Chromosomal Location	16q22-q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TK2 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting TK2.

ID	Name	Drug Type	Targets	#Targets
DB02452	Thymidine-5'-Triphosphate	Small Molecule	TK1, TK2	2
DB02594	2'-Deoxycytidine	Small Molecule	DCK, TK2	2
DB04485	Deoxythymidine	Small Molecule	TK2	1

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