UniProt functional annotation for P05089



	UniProt functional annotation for P05089

UniProt code: P05089.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000305}.

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. {ECO:0000250|UniProtKB:Q61176, ECO:0000269|PubMed:15546957, ECO:0000269|PubMed:16709924, ECO:0000269|PubMed:19380772}.

Catalytic activity: Reaction=H2O + L-arginine = L-ornithine + urea; Xref=Rhea:RHEA:20569, ChEBI:CHEBI:15377, ChEBI:CHEBI:16199, ChEBI:CHEBI:32682, ChEBI:CHEBI:46911; EC=3.5.3.1; Evidence={ECO:0000269|PubMed:16141327, ECO:0000269|PubMed:17562323};

Cofactor: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:16141327, ECO:0000269|PubMed:17469833, ECO:0000269|PubMed:17562323, ECO:0000269|PubMed:18802628}; Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:16141327, ECO:0000269|PubMed:17469833, ECO:0000269|PubMed:17562323, ECO:0000269|PubMed:18802628};

Pathway: Nitrogen metabolism; urea cycle; L-ornithine and urea from L- arginine: step 1/1. {ECO:0000305|PubMed:16141327}.

Subunit: Homotrimer (PubMed:16141327, PubMed:17469833, PubMed:17562323, PubMed:18802628, PubMed:2241902). Interacts with CMTM6 (PubMed:28813417). {ECO:0000269|PubMed:16141327, ECO:0000269|PubMed:17469833, ECO:0000269|PubMed:17562323, ECO:0000269|PubMed:18802628, ECO:0000269|PubMed:2241902, ECO:0000269|PubMed:28813417}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:16141327}. Cytoplasmic granule {ECO:0000269|PubMed:15546957}. Note=Localized in azurophil granules of neutrophils (PubMed:15546957). {ECO:0000269|PubMed:15546957}.

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). {ECO:0000269|PubMed:15546957, ECO:0000269|PubMed:23749634}.

Induction: By arginine or homoarginine.

Disease: Argininemia (ARGIN) [MIM:207800]: 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, mental retardation, hypotonia, ataxia and progressive spastic quadriplegia. {ECO:0000269|PubMed:1463019, ECO:0000269|PubMed:22959135, ECO:0000269|PubMed:23859858, ECO:0000269|PubMed:7649538}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 2]: May be due to a competing acceptor splice site. {ECO:0000305}.

Similarity: Belongs to the arginase family. {ECO:0000255|PROSITE- ProRule:PRU00742}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000305}.



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. {ECO:0000250\|UniProtKB:Q61176, ECO:0000269\|PubMed:15546957, ECO:0000269\|PubMed:16709924, ECO:0000269\|PubMed:19380772}.


Catalytic activity:		Reaction=H2O + L-arginine = L-ornithine + urea; Xref=Rhea:RHEA:20569, ChEBI:CHEBI:15377, ChEBI:CHEBI:16199, ChEBI:CHEBI:32682, ChEBI:CHEBI:46911; EC=3.5.3.1; Evidence={ECO:0000269\|PubMed:16141327, ECO:0000269\|PubMed:17562323};
Cofactor:		Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269\|PubMed:16141327, ECO:0000269\|PubMed:17469833, ECO:0000269\|PubMed:17562323, ECO:0000269\|PubMed:18802628}; Note=Binds 2 manganese ions per subunit. {ECO:0000269\|PubMed:16141327, ECO:0000269\|PubMed:17469833, ECO:0000269\|PubMed:17562323, ECO:0000269\|PubMed:18802628};
Pathway:		Nitrogen metabolism; urea cycle; L-ornithine and urea from L- arginine: step 1/1. {ECO:0000305\|PubMed:16141327}.
Subunit:		Homotrimer (PubMed:16141327, PubMed:17469833, PubMed:17562323, PubMed:18802628, PubMed:2241902). Interacts with CMTM6 (PubMed:28813417). {ECO:0000269\|PubMed:16141327, ECO:0000269\|PubMed:17469833, ECO:0000269\|PubMed:17562323, ECO:0000269\|PubMed:18802628, ECO:0000269\|PubMed:2241902, ECO:0000269\|PubMed:28813417}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:16141327}. Cytoplasmic granule {ECO:0000269\|PubMed:15546957}. Note=Localized in azurophil granules of neutrophils (PubMed:15546957). {ECO:0000269\|PubMed:15546957}.
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). {ECO:0000269\|PubMed:15546957, ECO:0000269\|PubMed:23749634}.
Induction:		By arginine or homoarginine.
Disease:		Argininemia (ARGIN) [MIM:207800]: 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, mental retardation, hypotonia, ataxia and progressive spastic quadriplegia. {ECO:0000269\|PubMed:1463019, ECO:0000269\|PubMed:22959135, ECO:0000269\|PubMed:23859858, ECO:0000269\|PubMed:7649538}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 2]: May be due to a competing acceptor splice site. {ECO:0000305}.
Similarity:		Belongs to the arginase family. {ECO:0000255\|PROSITE- ProRule:PRU00742}.