Arg1

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.

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.

Involvement in disease

Argininemia

ARGIN

A rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, intellectual disability, hypotonia, ataxia and progressive spastic quadriplegia.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1.

Sequence similarities

Belongs to the arginase family.

Tissue specificity

Within the immune system initially reported to be selectively expressed in granulocytes (polymorphonuclear leukocytes [PMNs]) (PubMed:15546957). Also detected in macrophages mycobacterial granulomas (PubMed:23749634). Expressed in group2 innate lymphoid cells (ILC2s) during lung disease (PubMed:27043409).

Cellular localization

• Cytoplasm
• Cytoplasmic granule
• Localized in azurophil granules of neutrophils (PubMed:15546957).

Alternative names

• Arginase-1
• Liver-type arginase
• Type I arginase
• ARG1

Database links

• entrezGene:383
• omim:608313
• swissprot:P05089

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

• Oncology

Molecular weight

34735Da