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Arginase I

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1244

Nomenclature: Arginase I

Abbreviated Name: ARG1

Family: Arginase

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 322 6q23.2 ARG1 arginase 1
Mouse - 323 10 A4 Arg1 arginase, liver
Rat - 323 1p12 Arg1 arginase 1
Previous and Unofficial Names Click here for help
Liver arginase | AI type I arginase | PGIF | cytosolic arginase | arginase
Database Links Click here for help
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human Arginase-1 complexed with inhibitor 9.
PDB Id:  4HWW
Ligand:  compound 9 [PMID: 23472952]
Resolution:  1.3Å
Species:  Human
References:  4
Enzyme Reaction Click here for help
EC Number: 3.5.3.1
Description Reaction Reference
L-arginine + H2O <=> L-ornithine + urea

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
2(S)-amino-6-boronohexanoic acid Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pKd 2
pKd 8.3 (Kd 5x10-9 M) [2]
A1P Small molecule or natural product Hs Inhibition 5.7 pKd 3
pKd 5.7 (Kd 2x10-6 M) [3]
Description: Dissociation constant measured using surface plasmon resonance assay.
A1P Small molecule or natural product Primary target of this compound Hs Inhibition 5.4 pKi 3
pKi 5.4 (Ki 4x10-6 M) [3]
Description: Measured using an enzyme kinetics assay.
compound 9 [PMID: 23472952] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 4
pIC50 6.7 (IC50 2.23x10-7 M) [4]
Immunopharmacology Comments
The role of ARG1 in immuno-oncology is reviewed in [1].
Immuno Process Associations
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 4 GO processes, IEA only
GO:0042130 negative regulation of T cell proliferation IDA
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GO:0002250 adaptive immune response IEA
GO:0046007 negative regulation of activated T cell proliferation IEA
GO:2000552 negative regulation of T-helper 2 cell cytokine production IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
GO:2000552 negative regulation of T-helper 2 cell cytokine production IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 5 GO processes, IEA only
GO:0042130 negative regulation of T cell proliferation IDA
GO:0060336 negative regulation of interferon-gamma-mediated signaling pathway IMP
GO:0070965 positive regulation of neutrophil mediated killing of fungus IMP
click arrow to show/hide IEA associations
GO:0046007 negative regulation of activated T cell proliferation IEA
GO:2000552 negative regulation of T-helper 2 cell cytokine production IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes, IEA only
GO:0042130 negative regulation of T cell proliferation IDA
click arrow to show/hide IEA associations
GO:0046007 negative regulation of activated T cell proliferation IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0043312 neutrophil degranulation TAS
GO:0060336 negative regulation of interferon-gamma-mediated signaling pathway IMP
click arrow to show/hide IEA associations
GO:0045087 innate immune response IEA
GO:2000552 negative regulation of T-helper 2 cell cytokine production IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0042130 negative regulation of T cell proliferation IDA
GO:0043312 neutrophil degranulation TAS
click arrow to show/hide IEA associations
GO:0046007 negative regulation of activated T cell proliferation IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes, IEA only
GO:0060336 negative regulation of interferon-gamma-mediated signaling pathway IMP
click arrow to show/hide IEA associations
GO:0071353 cellular response to interleukin-4 IEA
GO:2000552 negative regulation of T-helper 2 cell cytokine production IEA

References

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1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov, 14 (9): 603-22. [PMID:26228631]

2. Baggio R, Elbaum D, Kanto ZF, Carroll PJ, Cavalli RC, Ash DE, Christianson DW. (1997) Inhibition of Mn2+2-Arginase by Borate Leads to the Design of a Transition State Analogue Inhibitor, 2(S)-Amino-6-boronohexanoic Acid. J Am Chem Soc, 119 (34): 8107–8108.

3. Ilies M, Di Costanzo L, North ML, Scott JA, Christianson DW. (2010) 2-aminoimidazole amino acids as inhibitors of the binuclear manganese metalloenzyme human arginase I. J Med Chem, 53 (10): 4266-76. [PMID:20441173]

4. Van Zandt MC, Whitehouse DL, Golebiowski A, Ji MK, Zhang M, Beckett RP, Jagdmann GE, Ryder TR, Sheeler R, Andreoli M et al.. (2013) Discovery of (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid and congeners as highly potent inhibitors of human arginases I and II for treatment of myocardial reperfusion injury. J Med Chem, 56 (6): 2568-80. [PMID:23472952]

How to cite this page

Arginase: Arginase I. Last modified on 16/03/2017. Accessed on 11/05/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1244.