Tchem ARG1 Arginase-1

Protein Summary

Description

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. Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exist (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type I isoform encoded by this gene, is a cytosolic enzyme and expressed predominantly in the liver as a component of the urea cycle. Inherited deficiency of this enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• P05089
• A6NEA0
• Q5JWT5
• Q5JWT6
• Q8TE72
• Q9BS50

Gene Name

• ARG1

Ensembl ID

• ENST00000356962
• ENSP00000349446
• ENSG00000118520
• ENST00000368087
• ENSP00000357066
• ENST00000640973
• ENSP00000492623

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.98
biological process	0.97
interacting protein	0.81
biological term	0.76
chemical	0.73

Protein Classes

PANTHER Classes

Protein / Hydrolase / Arginase-1

DTO Classes

Protein / Enzyme / Hydrolase / Arginase-1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1600.48   (req: < 5)

Gene RIFs: 117   (req: <= 3)

Antibodies: 1071   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1600.48   (req: >= 5)

Gene RIFs: 117   (req: > 3)

Antibodies: 1071   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 40

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 96

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (96)

Explore Active Ligands

1 – 10 of 96

2-(S)-amino-6-boronohexanoic acid

ARG1Tchem Enzyme

pKi : 8.07

CHEMBL2326089

ARG1Tchem Enzyme

pIC50 : 7.75

CHEMBL2418830

ARG1Tchem Enzyme

pIC50 : 7.77

CHEMBL2418831

ARG1Tchem Enzyme

pIC50 : 7.68

CHEMBL2418991

ARG1Tchem Enzyme

pIC50 : 7.66

CHEMBL2418829

ARG1Tchem Enzyme

pIC50 : 7.62

L-nor-N-hydroxyarginine

ARG1Tchem Enzyme

pKi : 7.29

CHEMBL2326090

ARG1Tchem Enzyme

pIC50 : 7.22

CHEMBL2418828

ARG1Tchem Enzyme

pIC50 : 7.1

CHEMBL2326087

ARG1Tchem Enzyme

pIC50 : 7

Protein-Protein Interactions (296)

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1 – 10 of 296

• See Interactions on String-DB

CCDC51

Tdark

Novelty:  1.19203634

p_int:  0.989796093

p_ni:  0.010203907

Score:  0.202

Data Source:  BioPlex,STRINGDB

ZIC1

Tbio

Family:  TF

Novelty:  0.00491601

p_int:  0.961894231

p_ni:  0.038105769

Data Source:  BioPlex

GPR18

Tchem

Family:  GPCR

Novelty:  0.0178347

p_int:  0.871080291

p_ni:  0.128919709

Score:  0.252

Data Source:  BioPlex,STRINGDB

FCF1

Tdark

Novelty:  0.04202976

p_int:  0.832020925

p_ni:  0.167979075

Data Source:  BioPlex

TEFM

Tbio

Novelty:  0.10836617

p_int:  0.824128095

p_ni:  0.175871905

Data Source:  BioPlex

CFAP298

Tbio

Novelty:  0.1550579

p_int:  0.820156076

p_ni:  0.179843924

Data Source:  BioPlex

MCL1

Tchem

Novelty:  0.00046181

p_int:  0.810916811

p_ni:  0.189083189

Score:  0.225

Data Source:  BioPlex,STRINGDB

NPPA

Tchem

Novelty:  0.00046693

p_int:  0.79534002

p_ni:  0.204659979

Score:  0.208

Data Source:  BioPlex,STRINGDB

ARG2

Tchem

Family:  Enzyme

Novelty:  0.0006655

p_int:  0.792387839

p_ni:  0.207612161

Score:  0.876

Data Source:  BioPlex,STRINGDB

SPICE1

Tbio

Novelty:  0.19045168

p_int:  0.770778838

p_ni:  0.229221162

Score:  0.189

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (1)

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Downstream (1)

1 – 1 of 1

ODC1

Tclin

Family:  Enzyme

KEGG Distance:  1

Common Pathways:  2

1: Arginine and proline metabolism

2: Metabolic pathways

Pathways (24)

Reactome (6)

KEGG (5)

PathwayCommons (6)

UniProt (1)

WikiPathways (6)

Immune System (R-HSA-168256)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Reactome	Neutrophil degranulation	543 targets	R-HSA-6798695

Name	Explore in Pharos	Explore in Source
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249
Metabolism	2112 targets	R-HSA-1430728
Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Neutrophil degranulation	543 targets	R-HSA-6798695

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (50)

Functions (2)

Components (10)

Processes (38)

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1 – 2 of 2

GO Term	Evidence	Assigned by
arginase activity	Inferred from Experiment (EXP)	Reactome
manganese ion binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations (null)

No disease associations found

GWAS Traits (11)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glomerular filtration rate	EFO_0005208	7	6	7	6.7	94.2
vitamin D measurement	EFO_0004631	4	4	4		83.3
L-arginine measurement	EFO_0006524	1	1	0	4	71.3
type II diabetes mellitus	EFO_0001360	4	3	3	1.1	70
creatinine measurement	EFO_0004518	2	2	2		69.1

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glomerular filtration rate	EFO_0005208	7	6.7	94.2
vitamin D measurement	EFO_0004631	4		83.3
L-arginine measurement	EFO_0006524	0	4	71.3
type II diabetes mellitus	EFO_0001360	3	1.1	70
creatinine measurement	EFO_0004518	2		69.1

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Adaptive immunity
Alternative splicing
Arginine metabolism
Complete proteome
Cytoplasm
Disease mutation
Hydrolase
Immunity
Innate immunity

GWAS Trait Find Similar Targets

No Header	No Header
alkaline phosphatase measurement
apolipoprotein A 1 measurement
body mass index
C-reactive protein measurement
creatinine measurement
glomerular filtration rate
high density lipoprotein cholesterol measurement
L-arginine measurement
testosterone measurement
type II diabetes mellitus

MGI Phenotype Find Similar Targets

No Header	No Header
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	arginase 1	VGNC:11033	462999
Macaque	arginase 1		710410
Mouse	arginase, liver	MGI:88070	11846
Rat	arginase 1	RGD:2150	29221
Dog	arginase 1	VGNC:38041	474823

Species	Name	OMA	EggNOG	Inparanoid
Chimp	arginase 1
Macaque	arginase 1
Mouse	arginase, liver
Rat	arginase 1
Dog	arginase 1

Publication Statistics

PubMed Score 1600.48

PubMed score by year

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PubTator Score 369.66

PubTator score by year

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Related Publications

Text Mined References (147)

GeneRif Annotations (117)

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PMID	Year	Title