TISIDB

Summary
Symbol	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
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	Secreted Note=Secreted by most body fluids including serum and CSF. Also by adipocytes and numerous cancer cells.
Domain	PF01223 DNA/RNA non-specific endonuclease PF01663 Type I phosphodiesterase / nucleotide pyrophosphatase PF01033 Somatomedin B domain
Function	Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001667 ameboidal-type cell migration GO:0006644 phospholipid metabolic process GO:0006898 receptor-mediated endocytosis GO:0009395 phospholipid catabolic process GO:0010631 epithelial cell migration GO:0010632 regulation of epithelial cell migration GO:0010634 positive regulation of epithelial cell migration GO:0016042 lipid catabolic process GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0022604 regulation of cell morphogenesis GO:0030335 positive regulation of cell migration GO:0031346 positive regulation of cell projection organization GO:0034638 phosphatidylcholine catabolic process GO:0040017 positive regulation of locomotion GO:0044242 cellular lipid catabolic process GO:0045765 regulation of angiogenesis GO:0046434 organophosphate catabolic process GO:0046470 phosphatidylcholine metabolic process GO:0048514 blood vessel morphogenesis GO:0050730 regulation of peptidyl-tyrosine phosphorylation GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0051272 positive regulation of cellular component movement GO:0072673 lamellipodium morphogenesis GO:0090130 tissue migration GO:0090132 epithelium migration GO:0090305 nucleic acid phosphodiester bond hydrolysis GO:0097164 ammonium ion metabolic process GO:0097581 lamellipodium organization GO:1901342 regulation of vasculature development GO:1902743 regulation of lamellipodium organization GO:1902745 positive regulation of lamellipodium organization GO:2000147 positive regulation of cell motility GO:2000392 regulation of lamellipodium morphogenesis GO:2000394 positive regulation of lamellipodium morphogenesis
Molecular Function	GO:0001871 pattern binding GO:0004518 nuclease activity GO:0004527 exonuclease activity GO:0004528 phosphodiesterase I activity GO:0004551 nucleotide diphosphatase activity GO:0004620 phospholipase activity GO:0004622 lysophospholipase activity GO:0005044 scavenger receptor activity GO:0008081 phosphoric diester hydrolase activity GO:0008134 transcription factor binding GO:0016298 lipase activity GO:0030246 carbohydrate binding GO:0030247 polysaccharide binding GO:0038024 cargo receptor activity GO:0042578 phosphoric ester hydrolase activity GO:0047391 alkylglycerophosphoethanolamine phosphodiesterase activity GO:0052689 carboxylic ester hydrolase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00565 Ether lipid metabolism
Reactome	R-HSA-74160: Gene Expression R-HSA-450520: HuR (ELAVL1) binds and stabilizes mRNA R-HSA-1430728: Metabolism R-HSA-196854: Metabolism of vitamins and cofactors R-HSA-196849: Metabolism of water-soluble vitamins and cofactors R-HSA-450531: Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-199220: Vitamin B5 (pantothenate) metabolism

Summary
Symbol	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ENPP2 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	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
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

[ TOP ]

Statistical results of ENPP2 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	Sensitive to T cell-mediated killing
24476824	shRNA	melanoma	B16	Primary screen	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
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

[ TOP ]

Points in the above scatter plot represent the expression difference of ENPP2 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	-0.941	0.173
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.959	0.637
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.939	0.584
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.016	0.965
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.226	0.89
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.321	0.874
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.791	0.152
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.59	0.752
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.01	0.629
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.12	0.941
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	0.544	0.813
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.04	0.81

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of ENPP2 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	5.5	-5.5	0.572
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	6.8	-6.8	0.304
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	22.2	6.2	16	0.53
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	50	14.3	35.7	0.491
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ENPP2. 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	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ENPP2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ENPP2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ENPP2. 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	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ENPP2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ENPP2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ENPP2
Name	ectonucleotide pyrophosphatase/phosphodiesterase 2
Aliases	PD-IALPHA; autotaxin; PDNP2; ATX-X; LysoPLD; NPP2; E-NPP 2; autotaxin-t; extracellular lysophospholipase D; ......
Chromosomal Location	8q24.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ENPP2 collected from DrugBank database.

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

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