Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7ZQEV)

• DTT Name: Arginase-1 (ARG1)
• Synonyms: Liver-type arginase; Type I arginase
• Gene Name: ARG1
• DTT Type: Clinical trial target; [1]
• UniProt ID: ARGI1_HUMAN
• TTD ID: T63224
• EC Number: EC 3.5.3.1
• Sequence:
  MSAKSRTIGIIGAPFSKGQPRGGVEEGPTVLRKAGLLEKLKEQECDVKDYGDLPFADIPN
  DSPFQIVKNPRSVGKASEQLAGKVAEVKKNGRISLVLGGDHSLAIGSISGHARVHPDLGV
  IWVDAHTDINTPLTTTSGNLHGQPVSFLLKELKGKIPDVPGFSWVTPCISAKDIVYIGLR
  DVDPGEHYILKTLGIKYFSMTEVDRLGIGKVMEETLSYLLGRKKRPIHLSFDVDGLDPSF
  TPATGTPVVGGLTYREGLYITEEIYKTGLLSGLDIMEVNPSLGKTPEEVTRTVNTAVAIT
  LACFGLAREGNHKPIDYLNPPK
• 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}.
• KEGG Pathway: 383 (hsa)
• Reactome Pathway:
  (R-HSA-6798695)
  (R-HSA-70635)
• BioCyc Pathway: MetaCyc:HS04231-MONOMER

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pegzilarginase	DMLI2DZ	Arginase 1 deficiency	5C50.A2	Phase 3	[1]

References

• [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.