1. Gene Aliases

ARG1, Arginase 1, Arginase-1, Liver-Type Arginase, Arginase, Liver, Type I Arginase, EC 3.5.3.1

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=ARG1&keywords=Arg1].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

adaptive immune response [An immune response mediated by cells expressing specific receptors for antigens produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory). GO:0002250]

arginine catabolic process to ornithine [The chemical reactions and pathways resulting in the breakdown of arginine into other compounds, including ornithine. GO:0019547]

arginine metabolic process [The chemical reactions and pathways involving arginine, 2-amino-5-(carbamimidamido)pentanoic acid. GO:0006525]

cellular response to dexamethasone stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a dexamethasone stimulus. GO:0071549]

cellular response to glucagon stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucagon stimulus. GO:0071377]

cellular response to hydrogen peroxide [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus. GO:0070301]

cellular response to interleukin-4 [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-4 stimulus. GO:0071353]

cellular response to lipopolysaccharide [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0071222]

cellular response to transforming growth factor beta stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus. GO:0071560]

collagen biosynthetic process [The chemical reactions and pathways resulting in the formation of collagen, any of a group of fibrous proteins of very high tensile strength that form the main component of connective tissue in animals. Collagen is highly enriched in glycine (some regions are 33% glycine) and proline, occurring predominantly as 3-hydroxyproline (about 20%). GO:0032964]

defense response to protozoan [Reactions triggered in response to the presence of a protozoan that act to protect the cell or organism. GO:0042832]

female pregnancy [The set of physiological processes that allow an embryo or foetus to develop within the body of a female animal. It covers the time from fertilization of a female ovum by a male spermatozoon until birth. GO:0007565]

innate immune response [Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. GO:0045087]

liver development [The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes. GO:0001889]

lung development [The process whose specific outcome is the progression of the lung over time, from its formation to the mature structure. In all air-breathing vertebrates the lungs are developed from the ventral wall of the oesophagus as a pouch which divides into two sacs. In amphibians and many reptiles the lungs retain very nearly this primitive sac-like character, but in the higher forms the connection with the esophagus becomes elongated into the windpipe and the inner walls of the sacs become more and more divided, until, in the mammals, the air spaces become minutely divided into tubes ending in small air cells, in the walls of which the blood circulates in a fine network of capillaries. In mammals the lungs are more or less divided into lobes, and each lung occupies a separate cavity in the thorax. GO:0030324]

mammary gland involution [The tissue remodeling that removes differentiated mammary epithelia during weaning. GO:0060056]

maternal process involved in female pregnancy [A reproductive process occurring in the mother that allows an embryo or fetus to develop within it. GO:0060135]

negative regulation of T cell proliferation [Any process that stops, prevents or reduces the rate or extent of T cell proliferation. GO:0042130]

negative regulation of T-helper 2 cell cytokine production [Any process that stops, prevents or reduces the frequency, rate or extent of T-helper 2 cell cytokine production. GO:2000552]

negative regulation of activated T cell proliferation [Any process that stops, prevents or reduces the rate or extent of activated T cell proliferation. GO:0046007]

negative regulation of type II interferon-mediated signaling pathway [Any process that decreases the rate, frequency or extent of an interferon-gamma-mediated signaling pathway. GO:0060336]

positive regulation of endothelial cell proliferation [Any process that activates or increases the rate or extent of endothelial cell proliferation. GO:0001938]

positive regulation of neutrophil mediated killing of fungus [Any process that increases the frequency, rate or extent of the directed killing of a fungal cell by a neutrophil. GO:0070965]

regulation of L-arginine import across plasma membrane [Any process that modulates the frequency, rate or extent of L-arginine import across plasma membrane. GO:1905541]

response to amine [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amine stimulus. An amine is a compound formally derived from ammonia by replacing one, two or three hydrogen atoms by hydrocarbyl groups. GO:0014075]

response to amino acid [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amino acid stimulus. An amino acid is a carboxylic acids containing one or more amino groups. GO:0043200]

response to axon injury [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an axon injury stimulus. GO:0048678]

response to cadmium ion [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cadmium (Cd) ion stimulus. GO:0046686]

response to herbicide [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a herbicide stimulus. Herbicides are chemicals used to kill or control the growth of plants. GO:0009635]

response to lipopolysaccharide [Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0032496]

response to manganese ion [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a manganese ion stimulus. GO:0010042]

response to methylmercury [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a methylmercury stimulus. GO:0051597]

response to peptide hormone [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptide hormone stimulus. A peptide hormone is any of a class of peptides that are secreted into the blood stream and have endocrine functions in living animals. GO:0043434]

response to selenium ion [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from selenium ion. GO:0010269]

response to steroid hormone [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a steroid hormone stimulus. GO:0048545]

response to vitamin A [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin A stimulus. GO:0033189]

response to vitamin E [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin E stimulus. GO:0033197]

response to xenobiotic stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. GO:0009410]

response to zinc ion [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a zinc ion stimulus. GO:0010043]

urea cycle [The sequence of reactions by which arginine is synthesized from ornithine, then cleaved to yield urea and regenerate ornithine. The overall reaction equation is NH3 + CO2 + aspartate + 3 ATP + 2 H2O = urea + fumarate + 2 ADP + 2 phosphate + AMP + diphosphate. GO:0000050]

MSigDB Signatures:

REACTOME_NEUTROPHIL_DEGRANULATION: Neutrophil degranulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NEUTROPHIL_DEGRANULATION.html]

WP_UREA_CYCLE_AND_RELATED_DISEASES: Urea cycle and related diseases [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_UREA_CYCLE_AND_RELATED_DISEASES.html]

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

WP_UREA_CYCLE_AND_ASSOCIATED_PATHWAYS: Urea cycle and associated pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_UREA_CYCLE_AND_ASSOCIATED_PATHWAYS.html]

REACTOME_UREA_CYCLE: Urea cycle [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_UREA_CYCLE.html]

WP_SPINAL_CORD_INJURY: Spinal cord injury [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_SPINAL_CORD_INJURY.html]

KEGG_ARGININE_AND_PROLINE_METABOLISM: Arginine and proline metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_ARGININE_AND_PROLINE_METABOLISM.html]

KEGG_MEDICUS_REFERENCE_UREA_CYCLE: Pathway Definition from KEGG: NH3 -- CPS1 >> OTC >> ASS1 >> ASL >> ARG1/2 -> Urea+Ornithine [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MEDICUS_REFERENCE_UREA_CYCLE.html]

7. Gene Descriptions

NCBI Gene Summary: Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exist (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type I isoform encoded by this gene, is a cytosolic enzyme and expressed predominantly in the liver as a component of the urea cycle. Inherited deficiency of this enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

GeneCards Summary: ARG1 (Arginase 1) is a Protein Coding gene. Diseases associated with ARG1 include Argininemia and Autoimmune Hepatitis. Among its related pathways are superpathway of L-citrulline metabolism and Innate Immune System. Gene Ontology (GO) annotations related to this gene include manganese ion binding and arginase activity. An important paralog of this gene is ARG2.

UniProtKB/Swiss-Prot Summary: 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. 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 [PMID: 15546957, PMID: 16709924, PMID: 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. In humans, the immunological role in the monocytic/macrophage/dendritic cell (DC) lineage is unsure.

8. Cellular Location of Gene Product

Selective expression in liver and subsets of bone marrow cells. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000118520/subcellular]

9. Mechanistic Information

Summary

Arg1, encoding arginase 1, is upregulated in lung diseases and toxicities as a response to inflammatory and stress conditions, reflecting its role in modulating immune responses and tissue repair [CS: 8]. In lung conditions like severe pneumonia and COPD, the increased expression of Arg1 leads to enhanced arginase activity, which degrades extracellular arginine [CS: 7]. This degradation reduces arginine availability for nitric oxide synthase (NOS), thereby limiting nitric oxide (NO) production [CS: 7]. NO is a critical mediator in inflammatory responses and vasodilation [CS: 9]. By reducing NO levels, Arg1 helps to modulate excessive inflammation and vascular changes, which are common in lung pathologies [CS: 6].

Additionally, the upregulation of Arg1 in myeloid cells, as seen in conditions like pulmonary arterial hypertension (PAH) and non-small cell lung cancer (NSCLC), leads to arginine depletion in the microenvironment [CS: 7]. This depletion suppresses T cell and natural killer (NK) cell proliferation and cytokine secretion, thereby modulating the immune response [CS: 6]. Arg1's role in collagen synthesis, through its metabolic products like proline, might also aid tissue repair during lung injury and remodeling, essential for recovery from lung damage [CS: 5].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: liver (tissue enriched) [https://www.proteinatlas.org/ENSG00000118520/tissue]

Cell type enchanced: hepatocytes (cell type enriched) [https://www.proteinatlas.org/ENSG00000118520/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest