Arginase I | Arginase | IUPHAR/BPS Guide to PHARMACOLOGY

Arginase I

Target id: 1244

Nomenclature: Arginase I

Abbreviated Name: ARG1

Family: Arginase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Arginase I has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - - ARG1 arginase 1
Mouse - - Arg1 arginase, liver
Rat - - Arg1 arginase 1
Previous and Unofficial Names
Liver arginase | AI type I arginase | PGIF | cytosolic arginase | arginase
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
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
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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
2(S)-amino-6-boronohexanoic acid Hs Inhibition 8.3 pKd 2
pKd 8.3 (Kd 5x10-9 M) [2]
A1P Hs Inhibition 5.7 pKd 3
pKd 5.7 (Kd 2x10-6 M) [3]
Description: Dissociation constant measured using surface plasmon resonance assay.
A1P 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] 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
click arrow to show/hide IEA associations
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 19/09/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1244.