Browse ARG1

Summary
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
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 Cytoplasm Cytoplasmic granule Note=Localized in azurophil granules of neutrophils (PubMed:15546957).
Domain PF00491 Arginase family
Function

Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys. ; FUNCTION: Functions in L-arginine homeostasis in nonhepatic tissues characterized by the competition between nitric oxide synthase (NOS) and arginase for the available intracellular substrate arginine. Arginine metabolism is a critical regulator of innate and adaptive immune responses. Involved in an antimicrobial effector pathway in polymorphonuclear granulocytes (PMN). Upon PMN cell death is liberated from the phagolysosome and depletes arginine in the microenvironment leading to suppressed T cell and natural killer (NK) cell proliferation and cytokine secretion (PubMed:15546957, PubMed:16709924, PubMed:19380772). In group 2 innate lymphoid cells (ILC2s) promotes acute type 2 inflammation in the lung and is involved in optimal ILC2 proliferation but not survival (By similarity). In humans, the immunological role in the monocytic/macrophage/dendritic cell (DC) lineage is unsure.

> Gene Ontology
 
Biological Process GO:0000050 urea cycle
GO:0000302 response to reactive oxygen species
GO:0001101 response to acid chemical
GO:0001889 liver development
GO:0001935 endothelial cell proliferation
GO:0001936 regulation of endothelial cell proliferation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0002237 response to molecule of bacterial origin
GO:0006520 cellular amino acid metabolic process
GO:0006525 arginine metabolic process
GO:0006527 arginine catabolic process
GO:0006591 ornithine metabolic process
GO:0006865 amino acid transport
GO:0006979 response to oxidative stress
GO:0007565 female pregnancy
GO:0007568 aging
GO:0007584 response to nutrient
GO:0009063 cellular amino acid catabolic process
GO:0009064 glutamine family amino acid metabolic process
GO:0009065 glutamine family amino acid catabolic process
GO:0009635 response to herbicide
GO:0009636 response to toxic substance
GO:0009991 response to extracellular stimulus
GO:0010035 response to inorganic substance
GO:0010038 response to metal ion
GO:0010042 response to manganese ion
GO:0010043 response to zinc ion
GO:0010269 response to selenium ion
GO:0010958 regulation of amino acid import
GO:0010963 regulation of L-arginine import
GO:0014075 response to amine
GO:0015837 amine transport
GO:0015849 organic acid transport
GO:0016054 organic acid catabolic process
GO:0019547 arginine catabolic process to ornithine
GO:0019627 urea metabolic process
GO:0022612 gland morphogenesis
GO:0030323 respiratory tube development
GO:0030324 lung development
GO:0030879 mammary gland development
GO:0031667 response to nutrient levels
GO:0031960 response to corticosteroid
GO:0032496 response to lipopolysaccharide
GO:0032890 regulation of organic acid transport
GO:0032963 collagen metabolic process
GO:0032964 collagen biosynthetic process
GO:0033189 response to vitamin A
GO:0033197 response to vitamin E
GO:0033273 response to vitamin
GO:0033762 response to glucagon
GO:0034599 cellular response to oxidative stress
GO:0034614 cellular response to reactive oxygen species
GO:0042493 response to drug
GO:0042542 response to hydrogen peroxide
GO:0043090 amino acid import
GO:0043091 L-arginine import
GO:0043092 L-amino acid import
GO:0043200 response to amino acid
GO:0043434 response to peptide hormone
GO:0044236 multicellular organism metabolic process
GO:0044259 multicellular organismal macromolecule metabolic process
GO:0044282 small molecule catabolic process
GO:0044706 multi-multicellular organism process
GO:0046395 carboxylic acid catabolic process
GO:0046686 response to cadmium ion
GO:0048545 response to steroid hormone
GO:0048678 response to axon injury
GO:0048732 gland development
GO:0048771 tissue remodeling
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050679 positive regulation of epithelial cell proliferation
GO:0051259 protein oligomerization
GO:0051260 protein homooligomerization
GO:0051384 response to glucocorticoid
GO:0051597 response to methylmercury
GO:0051952 regulation of amine transport
GO:0051955 regulation of amino acid transport
GO:0060056 mammary gland involution
GO:0060135 maternal process involved in female pregnancy
GO:0060443 mammary gland morphogenesis
GO:0060541 respiratory system development
GO:0061008 hepaticobiliary system development
GO:0070206 protein trimerization
GO:0070207 protein homotrimerization
GO:0070301 cellular response to hydrogen peroxide
GO:0070670 response to interleukin-4
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071353 cellular response to interleukin-4
GO:0071375 cellular response to peptide hormone stimulus
GO:0071377 cellular response to glucagon stimulus
GO:0071383 cellular response to steroid hormone stimulus
GO:0071384 cellular response to corticosteroid stimulus
GO:0071385 cellular response to glucocorticoid stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071417 cellular response to organonitrogen compound
GO:0071548 response to dexamethasone
GO:0071549 cellular response to dexamethasone stimulus
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071941 nitrogen cycle metabolic process
GO:0090467 arginine import
GO:1901565 organonitrogen compound catabolic process
GO:1901605 alpha-amino acid metabolic process
GO:1901606 alpha-amino acid catabolic process
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1901654 response to ketone
GO:1901655 cellular response to ketone
GO:1902023 L-arginine transport
GO:1990267 response to transition metal nanoparticle
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
GO:0030145 manganese ion binding
Cellular Component GO:0005741 mitochondrial outer membrane
GO:0019867 outer membrane
GO:0031968 organelle outer membrane
GO:0043025 neuronal cell body
GO:0044297 cell body
> KEGG and Reactome Pathway
 
KEGG hsa00330 Arginine and proline metabolism
hsa01100 Metabolic pathways
hsa01230 Biosynthesis of amino acids
Reactome R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-1430728: Metabolism
R-HSA-71291: Metabolism of amino acids and derivatives
R-HSA-351202: Metabolism of polyamines
R-HSA-6798695: Neutrophil degranulation
R-HSA-70635: Urea cycle
Summary
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ARG1 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 ARG1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26740106Head and Neck Squamous Cell CarcinomaInhibit immunity (T cell function)Similarly, knockdown of Sema4D in an HNSCC cell line resulted in a loss of MDSC function as shown by a decrease in the production of the immune-suppressive cytokines arginase-1, TGF-β, and IL-10 by MDSC, concomitant with recovery of T cell proliferation and IFN-γ production following stimulation of CD3/CD28.
25967142Prostate CarcinomaInhibit immunity (T cell function)TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients. These effects depended on reduced expression and enzymatic activity of Arginase-1, a downstream STAT3 target gene and a potent T cell inhibitor.
22474024Colon CarcinomaInhibit immunity (T cell function)Experiments using small interfering RNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the regulation of the suppressive function of MDSCs by increasing inducible NO synthase, arginase-1, and reactive oxygen species levels and enhancing NF-κB activity.
19431148Non-small-cell lung carcinomaInhibit immunity (T cell function)Arginase 1 (ARG1) inhibits T-cell proliferation by degrading extracellular arginine, which results in decreased responsiveness of T cells to CD3/TCR stimulation.
23420584Malignant Splenic NeoplasmInhibit immunity (T cell function)Here, we show that lactic acid, or more specifically the acidification it causes, increases arginase I (ARG1) expression in macrophages to inhibit T-cell proliferation and activation. We show that dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinases, targets macrophages to suppress activation of the IL-23/IL-17 pathway and the expression of ARG1 by lactic acid. DCA treatment decreased ARG1 expression in tumor-infiltrating immune cells and increased the number of IFN-γ-producing CD8+ T cells and NK cells in tumor-bearing mouse spleen.
29034589Colon CarcinomaInhibit immunity (T cell function)Giving angiotensin II receptor blockers (ARB) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells. ARB administration did not change the numbers of CD11b+ myeloid cells in tumors, but significantly reduced their T-cell inhibitory ability along with decreased production of various immunosuppressive factors including interleukin (IL)-6, IL-10, vascular endothelial growth factor (VEGF), and arginase by CD11b+ cells in tumors.
23665041Hepatocellular CarcinomaInhibit immunity (T cell function)Such CD14(+)HLA-DR(-/low) monocyte-derived MDSCs suppressed T-cell proliferation in an arginase-1 dependent fashion. HSC-induced development of CD14(+)HLA-DR(-/low) monocyte-derived MDSCs was not mediated by soluble factors, but required physical interaction and was abrogated by blocking CD44. Thus, our data suggest that local generation of MDSCs by liver-resident HSCs may contribute to immune suppression during inflammation and cancer in the liver.
29124314MelanomaInhibit immunityFurthermore, Foxp3 vaccination resulted in a significant reduction of arginase-1(Arg-1)-induced nitric oxide synthase (iNOS), reactive oxygen species (ROS) and suppressed MDSC activity.
25084511Cervical CarcinomaInhibit immunityThis study indicates that ASE activity and L-Arg degradation mechanisms of immunosuppression are present in cervical cancer.
21948231glioblastomaInhibit immunityThese data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI.
Summary
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
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 ARG1 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
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
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 ARG1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14121.1190.188
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1650.903
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)872.0780.0687
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2960.676
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.7950.55
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3220.819
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1270.903
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.7930.61
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.7950.614
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.1560.912
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.5630.76
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.8030.0171
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ARG1 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) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
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
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ARG1. 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
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ARG1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ARG1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ARG1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ARG1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ARG1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolARG1
Namearginase 1
Aliases arginase, liver; liver-type arginase; type I arginase; Arginase-1
Chromosomal Location6q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ARG1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ARG1.
ID Name Drug Type Targets #Targets
DB00129OrnithineSmall MoleculeARG1, ARG2, GATM, OAT, OAZ1, OAZ2, OAZ3, OTC, SLC25A15, SLC25A2, S ......14
DB019832(S)-Amino-6-Boronohexanoic AcidSmall MoleculeARG11
DB02381nor-NOHASmall MoleculeARG11
DB02499Dinor-N(Omega)-Hydroxy-L-ArginineSmall MoleculeARG11
DB02689S-{2-[Amino(Dihydroxy)-Lambda~4~-Sulfanyl]Ethyl}-D-CysteineSmall MoleculeARG11
DB03144N-Omega-Hydroxy-L-ArginineSmall MoleculeARG1, NOS1, NOS2, NOS34
DB03731S-2-(Boronoethyl)-L-CysteineSmall MoleculeARG1, ARG22
DB03904UreaSmall MoleculeARG1, CA2, CTNNB13
DB04197Descarboxy-nor-N(Omega)-Hydroxy-L-ArginineSmall MoleculeARG11
DB04530S,S-(2-Hydroxyethyl)ThiocysteineSmall MoleculeARG1, CYTH2, PDE1B, PDE4B, PIM1, PRKACA, SERPINB5, SNX3, TYMS9
DB04585DEHYDRO-2(S)-AMINO-6-BORONOHEXANOIC ACIDSmall MoleculeARG11
DB04648S-propylamine-L-cysteineSmall MoleculeARG11
DB06757ManganeseSmall MoleculeARG1, IDH3A, IDH3G, TAB1, TF5