Browse ARG2

Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
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
 
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
 
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
 
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
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
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
 
  Literatures describing the relation between ARG2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26054597NeuroblastomaInhibit immunity (T cell function)Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1820.595
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2140.885
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.4550.594
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4280.327
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0630.966
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.0450.55
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1730.616
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0170.989
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.3250.8
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-2.4750.0482
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-1.960.224
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1230.489
> Mutation difference between responders and non-responders
 
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/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
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
 
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
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
 
> Receptor
 
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ARG2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ARG2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolARG2
Namearginase 2
Aliases arginase, type II; L-arginine amidinohydrolase; L-arginine ureahydrolase; kidney arginase; kidney-type argin ......
Chromosomal Location14q24.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ARG2 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ARG2.
ID Name Drug Type Targets #Targets
DB00125L-ArginineSmall MoleculeARG2, ASL, ASS1, AZIN2, NOS2, NOS3, SLC7A1, SLC7A3, SLC7A49
DB00129OrnithineSmall MoleculeARG1, ARG2, GATM, OAT, OAZ1, OAZ2, OAZ3, OTC, SLC25A15, SLC25A2, S ......14
DB03731S-2-(Boronoethyl)-L-CysteineSmall MoleculeARG1, ARG22