TISIDB

Summary
Symbol	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
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	PF00491 Arginase family
Function	May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4(+) and CD8(+) T cells (PubMed:27745970). May suppress inflammation-related signaling in asthmatic airway epithelium (PubMed:27214549). May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism (By similarity). In fetal dendritic cells may play a role in promoting immune suppression and T cell TNF-alpha production during gestation (PubMed:28614294). Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction (PubMed:22928666). Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling (PubMed:25484082). Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity (PubMed:23832324). Since NOS is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase-2 plays a role in both male and female sexual arousal (PubMed:12859189).

> Gene Ontology [ TOP ]
Biological Process	GO:0000050 urea cycle GO:0001655 urogenital system development GO:0001657 ureteric bud development GO:0001822 kidney development GO:0001823 mesonephros development GO:0003012 muscle system process GO:0006520 cellular amino acid metabolic process GO:0006525 arginine metabolic process GO:0006809 nitric oxide biosynthetic process GO:0006936 muscle contraction GO:0006941 striated muscle contraction GO:0009064 glutamine family amino acid metabolic process GO:0019627 urea metabolic process GO:0046209 nitric oxide metabolic process GO:0071941 nitrogen cycle metabolic process GO:0072001 renal system development GO:0072073 kidney epithelium development GO:0072163 mesonephric epithelium development GO:0072164 mesonephric tubule development GO:0072593 reactive oxygen species metabolic process GO:1901605 alpha-amino acid metabolic process GO:1903409 reactive oxygen species biosynthetic process GO:2001057 reactive nitrogen species metabolic process
Molecular Function	GO:0004053 arginase activity GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds GO:0016813 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines
Cellular Component	GO:0005759 mitochondrial matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00330 Arginine and proline metabolism hsa01100 Metabolic pathways hsa01230 Biosynthesis of amino acids
Reactome	R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives R-HSA-351202: Metabolism of polyamines R-HSA-70635: Urea cycle

Summary
Symbol	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ARG2 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 ARG2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26054597	Neuroblastoma	Inhibit immunity (T cell function)	Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.

Summary
Symbol	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
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 ARG2 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	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
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 ARG2 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	-0.182	0.595
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.214	0.885
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.455	0.594
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.428	0.327
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.063	0.966
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.045	0.55
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.173	0.616
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.017	0.989
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.325	0.8
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-2.475	0.0482
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	-1.96	0.224
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.123	0.489

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ARG2 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ARG2. 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	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ARG2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ARG2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ARG2. 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	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ARG2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ARG2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ARG2
Name	arginase 2
Aliases	arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location	14q24.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ARG2 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting ARG2.

ID	Name	Drug Type	Targets	#Targets
DB00125	L-Arginine	Small Molecule	ARG2, ASL, ASS1, AZIN2, NOS2, NOS3, SLC7A1, SLC7A3, SLC7A4	9
DB00129	Ornithine	Small Molecule	ARG1, ARG2, GATM, OAT, OAZ1, OAZ2, OAZ3, OTC, SLC25A15, SLC25A2, S ......	14
DB03731	S-2-(Boronoethyl)-L-Cysteine	Small Molecule	ARG1, ARG2	2

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