Arginase-1 (ARG1)
The protein contains 322 amino acids for an estimated molecular weight of 34735 Da.
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. (updated: Dec. 20, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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No binding partner found
Biological Process
Adaptive immune response
Aging
Arginine catabolic process
Arginine catabolic process to ornithine
Cellular nitrogen compound metabolic process
Cellular response to dexamethasone stimulus
Cellular response to glucagon stimulus
Cellular response to hydrogen peroxide
Cellular response to interleukin-4
Cellular response to lipopolysaccharide
Cellular response to transforming growth factor beta stimulus
Collagen biosynthetic process
Defense response to protozoan
Innate immune response
Liver development
Lung development
Mammary gland involution
Maternal process involved in female pregnancy
Negative regulation of activated T cell proliferation
Negative regulation of interferon-gamma-mediated signaling pathway
Negative regulation of T cell proliferation
Negative regulation of T-helper 2 cell cytokine production
Neutrophil degranulation
Positive regulation of endothelial cell proliferation
Positive regulation of neutrophil mediated killing of fungus
Protein homotrimerization
Regulation of L-arginine import
Response to amine
Response to amino acid
Response to axon injury
Response to cadmium ion
Response to drug
Response to herbicide
Response to manganese ion
Response to methylmercury
Response to selenium ion
Response to vitamin A
Response to vitamin E
Response to zinc ion
Small molecule metabolic process
Urea cycle
The reference OMIM entry for this protein is 207800
Argininemia
Arginase deficiency
Hyperargininemia
Arg1 deficiency
A number sign (#) is used with this entry because argininemia is caused by mutation in the gene encoding liver arginase (ARG1; 608313).
DESCRIPTION
Arginase deficiency is an autosomal recessive inborn error of metabolism caused by a defect in the final step in the urea cycle, the hydrolysis of arginine to urea and ornithine. Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: ornithine transcarbamylase deficiency (311250), carbamyl phosphate synthetase deficiency (237300), argininosuccinate synthetase deficiency, or citrullinemia (215700), argininosuccinate lyase deficiency (207900), and arginase deficiency.CLINICAL FEATURES
Terheggen et al. (1969, 1970) described 2 sisters, aged 18 months and 5 years, with spastic paraplegia, epileptic seizures, and severe mental retardation. The parents were related. Arginine levels were high in the blood and spinal fluid of the patients, with intermediate elevations in both parents and in 2 healthy sibs. Arginase activity in red cells was very low in the patients and intermediate in the parents. In 1971 another affected girl was born into the family observed by Terheggen et al. (1972, 1975). There was late introduction of a low protein diet, but the infant developed severe mental retardation, athetosis, and spasticity. Cederbaum et al. (1977) reported a 7.5-year-old boy with progressive psychomotor retardation, behavior disturbance, and spasticity, who had growth arrest from age 3 years. Plasma arginine was increased, and red blood cell arginase activity was less than 1% of normal, whereas it was half-normal in both parents, 2 unaffected sibs, and in his paternal grandfather. Cederbaum et al. (1977) concluded that arginase deficiency is an autosomal recessive disorder. Michels and Beaudet (1978) reported an affected Mexican child with growth retardation, microcephaly, mental retardation, spasticity, and epileptiform discharges on EEG. In the province of Quebec, Qureshi et al. (1983) identified an affected French-Canadian family. Both parents showed activity of arginase 32 to 38% of normal. Walser (1983) stated that only 8 kindreds (with 13 patients) had been reported and that 4 of these (with 7 patients) were Spanish or Spanish-American. Jorda et al. (1986) described an unusually severe case of arginase deficiency in a Spanish infant who showed marked protein intolerance early in life. The levels of red cell arginase in the parents and 1 sister were consistent with heterozygosity. Brockstedt et al. (1990) described argininemia in a 4-year-old boy born of consanguineous Pakistani parents. He had microcephaly and spastic tetraplegia. Pregnancy and birth were uneventful and psychomotor development during the first 2 years of life were presumably normal. Vilarinho et al. (1990) described argininemia in a 5-year-old Portuguese boy who did not show spastic diplegia. His first manifestation, at 3.5 years of age, was a partial seizure for 15 minutes without loss of consciousness. Six months later he showed the same clinical features over a period of 15 days. The electroencephalogram showed partial left temporal and paracentral spikes. At 4.5 years of age he began to have episodes of vomiting, hypotonia, irritability, and ataxia. In a patient dying with severe argininemia, Grody et al. (1989) demonstrated total ... More on the omim web site
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 207800 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed