Target Information
Target General Information | Top | |||||
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Target ID |
T63224
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Target Name |
Arginase-1 (ARG1)
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Synonyms |
Liver-type arginase; Type I arginase
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Gene Name |
ARG1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Metabolism inborn error [ICD-11: 5C50] | |||||
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}.; 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}.
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UniProt ID | ||||||
EC Number |
EC 3.5.3.1
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Sequence |
MSAKSRTIGIIGAPFSKGQPRGGVEEGPTVLRKAGLLEKLKEQECDVKDYGDLPFADIPN
DSPFQIVKNPRSVGKASEQLAGKVAEVKKNGRISLVLGGDHSLAIGSISGHARVHPDLGV IWVDAHTDINTPLTTTSGNLHGQPVSFLLKELKGKIPDVPGFSWVTPCISAKDIVYIGLR DVDPGEHYILKTLGIKYFSMTEVDRLGIGKVMEETLSYLLGRKKRPIHLSFDVDGLDPSF TPATGTPVVGGLTYREGLYITEEIYKTGLLSGLDIMEVNPSLGKTPEEVTRTVNTAVAIT LACFGLAREGNHKPIDYLNPPK Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | Pegzilarginase | Drug Info | Phase 3 | Arginase 1 deficiency | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Replacement | [+] 1 Replacement drugs | + | ||||
1 | Pegzilarginase | Drug Info | [1] |
References | Top | |||||
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REF 1 | Preclinical safety and antitumor activity of the arginine-degrading therapeutic enzyme pegzilarginase, a PEGylated, cobalt-substituted recombinant human arginase 1. Transl Res. 2020 Mar;217:11-22. | |||||
REF 2 | ClinicalTrials.gov (NCT03921541) Efficacy and Safety of Pegzilarginase in Patients With Arginase 1 Deficiency. U.S. National Institutes of Health. |
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