TISIDB

Summary
Symbol	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
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	Isoform Long: Cell membrane; Multi-pass membrane protein.; SUBCELLULAR LOCATION: Isoform Short: Endoplasmic reticulum membrane; Multi-pass membrane protein.; SUBCELLULAR LOCATION: Isoform gamma: Endoplasmic reticulum membrane; Multi-pass membrane protein.
Domain	PF01150 GDA1/CD39 (nucleoside phosphatase) family
Function	In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Hydrolyzes ADP only to a marginal extent. The order of activity with different substrates is ATP > GTP > CTP = ITP > UTP >> ADP = UDP.

> Gene Ontology [ TOP ]
Biological Process	GO:0007596 blood coagulation GO:0007599 hemostasis GO:0009132 nucleoside diphosphate metabolic process GO:0009134 nucleoside diphosphate catabolic process GO:0009135 purine nucleoside diphosphate metabolic process GO:0009137 purine nucleoside diphosphate catabolic process GO:0009179 purine ribonucleoside diphosphate metabolic process GO:0009181 purine ribonucleoside diphosphate catabolic process GO:0009185 ribonucleoside diphosphate metabolic process GO:0009191 ribonucleoside diphosphate catabolic process GO:0019439 aromatic compound catabolic process GO:0030168 platelet activation GO:0034655 nucleobase-containing compound catabolic process GO:0044270 cellular nitrogen compound catabolic process GO:0046434 organophosphate catabolic process GO:0046700 heterocycle catabolic process GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:1901292 nucleoside phosphate catabolic process GO:1901361 organic cyclic compound catabolic process
Molecular Function	GO:0017110 nucleoside-diphosphatase activity
Cellular Component	GO:0005578 proteinaceous extracellular matrix GO:0005604 basement membrane GO:0005605 basal lamina GO:0044420 extracellular matrix component

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04742 Taste transduction hsa00230 Purine metabolism
Reactome	R-HSA-1430728: Metabolism R-HSA-15869: Metabolism of nucleotides R-HSA-8850843: Phosphate bond hydrolysis by NTPDase proteins

Summary
Symbol	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ENTPD2 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

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Literatures describing the relation between ENTPD2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28894087	Hepatocellular Carcinoma	Inhibit immunity	Mechanistically, we demonstrate that ENTPD2 converts extracellular ATP to 5'-AMP, which prevents the differentiation of MDSCs and therefore promotes the maintenance of MDSCs. We further find that ENTPD2 inhibition is able to mitigate cancer growth and enhance the efficiency and efficacy of immune checkpoint inhibitors.

Summary
Symbol	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
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 ENTPD2 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	NA/NS	NA/NS
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	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
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 ENTPD2 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	0.074	0.843
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.788	0.219
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.704	0.193
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.106	0.858
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.908	0.525
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.896	0.559
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.957	0.105
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.281	0.811
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.823	0.12
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-1.095	0.285
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	-1.101	0.407
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.329	0.176

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ENTPD2 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	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	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	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	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	11.1	6.2	4.9	1
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	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	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	7.1	-7.1	0.467
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	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ENTPD2. 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	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ENTPD2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ENTPD2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ENTPD2. 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	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ENTPD2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ENTPD2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ENTPD2
Name	ectonucleoside triphosphate diphosphohydrolase 2
Aliases	NTPDase-2; CD39-like-1; ecto-ATPase; CD39L1; CD39 antigen-like 1; NTPDase 2; ecto-ATP diphosphohydrolase 2; ......
Chromosomal Location	9q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ENTPD2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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