ARG1 arginase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ARG1provided by HGNC
Official Full Name: arginase 1provided by HGNC
Primary source: HGNC:HGNC:663
See related: Ensembl:ENSG00000118520 MIM:608313
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: 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]
Expression: Biased expression in liver (RPKM 237.4), bone marrow (RPKM 81.9) and 1 other tissue See more
Orthologs: mouse all

Genomic context

Location:: 6q23.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	6	NC_000006.12 (131573159..131584332)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (131894344..131905472)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

There was a significant difference in distribution of genotypes for rs2781666 and rs2781667 polymorphisms between patients and controls (p < 0.001 for each). Similarly, the variant T allele at both loci showed a significant association with the disease compared with subjects free of CAD (p < 0.0001 for each). The transmission-disequilibrium test revealed a significant association of rs2781666 and rs2781667 polymorphisms
Title: Arginase-1 Variants and the Risk of Familial Coronary Artery Disease in Subjects Originating from Pakistan.
This study indicated that high arginase activity and IL-13 concentration in the serum and ARG1 rs2781666 G/T genotype might increase the risk of asthma in susceptible population.
Title: Association of increased risk of asthma with elevated arginase & interleukin-13 levels in serum & rs2781666 G/T genotype of arginase I.
ARG1 might play a pivotal role as an oncogene in the progression of hepatocellular carcinoma through promoting the EMT process.
Title: The Oncogenic Role of ARG1 in Progression and Metastasis of Hepatocellular Carcinoma.
mutations in the epigenetic regulators TET2 and DNMT3A corresponded to high ARG1 expression and activity. These findings suggest ARG1 is a biomarker of immune dysregulation in early MDS and CMML
Title: Overexpression of Arginase 1 is linked to DNMT3A and TET2 mutations in lower-grade myelodysplastic syndromes and chronic myelomonocytic leukemia.
study of the significance of heat activation and the role of metal ions in human arginase
Title: Metal ions-induced stability and function of bimetallic human arginase-I, a therapeutically important enzyme.
TGF-beta1 and arginase-1 may play important roles in determining long-term graft survival.
Title: Relationship of Transforming Growth Factor-βl and Arginase-1 Levels with Long-term Survival after Kidney Transplantation.
These results showed that arginase controlled sFlt-1 elevation to some extent.
Title: Arginase controls soluble vascular endothelial growth factor receptor 1 (sFlt1) to maintain pregnancy homeostasis.
ARG1 gene polymorphisms and their association in individuals with essential hypertension in Pakistan has been presented.
Title: ARG1 Gene Polymorphisms and Their Association in Individuals with Essential Hypertension: A Case-Control Study.
A subset of well-differentiated hepatocellular carcinomas are arginase-1 negative.
Title: A subset of well-differentiated hepatocellular carcinomas are Arginase-1 negative.
The data in this study suggest that arginase I inhibition potentially represents a novel therapeutic target for the prevention and/or treatment of bronchopulmonary dysplasia-associated pulmonary hypertension.
Title: An arginase-1 SNP that protects against the development of pulmonary hypertension in bronchopulmonary dysplasia enhances NO-mediated apoptosis in lymphocytes.

Submit: New GeneRIF Correction See all GeneRIFs (117)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Arginase deficiency MedGen: C0268548 OMIM: 207800 GeneReviews: Arginase Deficiency, Urea Cycle Disorders Overview	Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study on obesity and obesity-related traits. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
New variants including ARG1 polymorphisms associated with C-reactive protein levels identified by genome-wide association and pathway analysis. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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ATF-2 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
ATF-2 transcription factor network, organism-specific biosystem
ATF-2 transcription factor network
Amino Acid metabolism, organism-specific biosystem (from WikiPathways)
Amino Acid metabolism, organism-specific biosystemA complete overview of the metabolism of all 20 amino acids
Amoebiasis, organism-specific biosystem (from KEGG)
Amoebiasis, organism-specific biosystemEntamoeba histolytica, an extracellular protozoan parasite is a human pathogen that invades the intestinal epithelium. Infection occurs on ingestion of contaminated water and food. The pathogenesis o...
Amoebiasis, conserved biosystem (from KEGG)
Amoebiasis, conserved biosystemEntamoeba histolytica, an extracellular protozoan parasite is a human pathogen that invades the intestinal epithelium. Infection occurs on ingestion of contaminated water and food. The pathogenesis o...
Arginine and proline metabolism, organism-specific biosystem (from KEGG)
Arginine and proline metabolism, organism-specific biosystem
Arginine and proline metabolism
Arginine and proline metabolism, conserved biosystem (from KEGG)
Arginine and proline metabolism, conserved biosystem
Arginine and proline metabolism
Arginine biosynthesis, organism-specific biosystem (from KEGG)
Arginine biosynthesis, organism-specific biosystem
Arginine biosynthesis
Arginine biosynthesis, conserved biosystem (from KEGG)
Arginine biosynthesis, conserved biosystem
Arginine biosynthesis
Biosynthesis of amino acids, organism-specific biosystem (from KEGG)
Biosynthesis of amino acids, organism-specific biosystemThis map presents a modular architecture of the biosynthesis pathways of twenty amino acids, which may be viewed as consisting of the core part and its extensions. The core part is the KEGG module fo...
Biosynthesis of amino acids, conserved biosystem (from KEGG)
Biosynthesis of amino acids, conserved biosystemThis map presents a modular architecture of the biosynthesis pathways of twenty amino acids, which may be viewed as consisting of the core part and its extensions. The core part is the KEGG module fo...
IL4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
IL4-mediated signaling events, organism-specific biosystem
IL4-mediated signaling events
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Metabolic pathways, organism-specific biosystem (from KEGG)
Metabolic pathways, organism-specific biosystem
Metabolic pathways
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of amino acids and derivatives, organism-specific biosystem (from REACTOME)
Metabolism of amino acids and derivatives, organism-specific biosystemThis group of reactions is responsible for: 1) the breakdown of amino acids; 2) the synthesis of urea from ammonia and amino groups generated by amino acid breakdown; 3) the synthesis of the ten amin...
Metabolism of polyamines, organism-specific biosystem (from REACTOME)
Metabolism of polyamines, organism-specific biosystemPolyamines is a family of molecules (i.e. putrescine, spermine, spermidine) derived from ornithine according to a decarboxylation/condensative process. More recently, it has been demonstrated that ar...
Neutrophil degranulation, organism-specific biosystem (from REACTOME)
Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
Polyamine biosynthesis, arginine => ornithine => putrescine, organism-specific biosystem (from KEGG)
Polyamine biosynthesis, arginine => ornithine => putrescine, organism-specific biosystemPathway module; Nucleotide and amino acid metabolism; Polyamine biosynthesis
Polyamine biosynthesis, arginine => ornithine => putrescine, conserved biosystem (from KEGG)
Polyamine biosynthesis, arginine => ornithine => putrescine, conserved biosystemPathway module; Nucleotide and amino acid metabolism; Polyamine biosynthesis
Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
Urea cycle, organism-specific biosystem (from REACTOME)
Urea cycle, organism-specific biosystemThe urea cycle yields urea, the major form in which excess nitrogen is excreted from the human body, and the amino acid arginine (Brusilow and Horwich 2001). It consists of four reactions: that of or...
Urea cycle, organism-specific biosystem (from KEGG)
Urea cycle, organism-specific biosystemPathway module; Nucleotide and amino acid metabolism; Arginine and proline metabolism
Urea cycle, conserved biosystem (from KEGG)
Urea cycle, conserved biosystemPathway module; Nucleotide and amino acid metabolism; Arginine and proline metabolism
Urea cycle and metabolism of amino groups, organism-specific biosystem (from WikiPathways)
Urea cycle and metabolism of amino groups, organism-specific biosystem
Urea cycle and metabolism of amino groups

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:196989 (e-PCR)
- UniSTS:155906

STS-M14502 (e-PCR)
- UniSTS:40466

RH46810 (e-PCR)
- UniSTS:82885

SHGC-16174 (e-PCR)
- UniSTS:79323

GDB:190876 (e-PCR)
- UniSTS:155628

SGC38314 (e-PCR)
- UniSTS:19443

Homology

Homologs of the ARG1 gene: The ARG1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, and frog.
Orthologs from Annotation Pipeline: 147 organisms have orthologs with human gene ARG1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
arginase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
manganese ion binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
adaptive immune response	IEA Inferred from Electronic Annotation more info
aging	IEA Inferred from Electronic Annotation more info
arginine catabolic process	TAS Traceable Author Statement more info	PubMed
arginine catabolic process to ornithine	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to dexamethasone stimulus	IEA Inferred from Electronic Annotation more info
cellular response to glucagon stimulus	IEA Inferred from Electronic Annotation more info
cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
cellular response to interleukin-4	IEA Inferred from Electronic Annotation more info
cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
cellular response to transforming growth factor beta stimulus	IEA Inferred from Electronic Annotation more info
collagen biosynthetic process	IEA Inferred from Electronic Annotation more info
defense response to protozoan	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
liver development	IEA Inferred from Electronic Annotation more info
lung development	IEA Inferred from Electronic Annotation more info
mammary gland involution	IEA Inferred from Electronic Annotation more info
maternal process involved in female pregnancy	IEA Inferred from Electronic Annotation more info
negative regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of T-helper 2 cell cytokine production	IEA Inferred from Electronic Annotation more info
negative regulation of activated T cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of interferon-gamma-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
neutrophil degranulation	TAS Traceable Author Statement more info
positive regulation of endothelial cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of neutrophil mediated killing of fungus	IMP Inferred from Mutant Phenotype more info	PubMed
protein homotrimerization	IEA Inferred from Electronic Annotation more info
regulation of L-arginine import	IEA Inferred from Electronic Annotation more info
response to amine	IEA Inferred from Electronic Annotation more info
response to amino acid	IEA Inferred from Electronic Annotation more info
response to axon injury	IEA Inferred from Electronic Annotation more info
response to cadmium ion	IEA Inferred from Electronic Annotation more info
response to herbicide	IEA Inferred from Electronic Annotation more info
response to manganese ion	IEA Inferred from Electronic Annotation more info
response to methylmercury	IEA Inferred from Electronic Annotation more info
response to selenium ion	IEA Inferred from Electronic Annotation more info
response to vitamin A	IEA Inferred from Electronic Annotation more info
response to vitamin E	IEA Inferred from Electronic Annotation more info
response to zinc ion	IEA Inferred from Electronic Annotation more info
urea cycle	IEA Inferred from Electronic Annotation more info
urea cycle	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
azurophil granule lumen	TAS Traceable Author Statement more info
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytosol	TAS Traceable Author Statement more info
extracellular region	TAS Traceable Author Statement more info
extracellular space	IDA Inferred from Direct Assay more info	PubMed
mitochondrial outer membrane	IEA Inferred from Electronic Annotation more info
neuron projection	IEA Inferred from Electronic Annotation more info
neuronal cell body	IEA Inferred from Electronic Annotation more info
nucleus	HDA more info	PubMed
specific granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: arginase-1

Names: arginase, liver; liver-type arginase; type I arginase

NP_000036.2

EC 3.5.3.1

NP_001231367.1

EC 3.5.3.1

NP_001355949.1

EC 3.5.3.1

XP_011534103.1

EC 3.5.3.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007086.2 RefSeqGene

Range

4980..16108

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000045.3 → NP_000036.2 arginase-1 isoform 2

See identical proteins and their annotated locations for NP_000036.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site at the 5' end of an exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AW236349, BC020653, BG217880, BG542163

Consensus CDS

CCDS5145.1

UniProtKB/Swiss-Prot

P05089

Related

ENSP00000357066.3, ENST00000368087.7

Conserved Domains (1) summary

cd11587
Location:9 → 303

Arginase-like; Arginase types I and II and arginase-like family
NM_001244438.1 → NP_001231367.1 arginase-1 isoform 1

See identical proteins and their annotated locations for NP_001231367.1

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as erythroid variant) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AW236349, AY074488, BC020653, BG217880, BG542163

Consensus CDS

CCDS59038.1

UniProtKB/Swiss-Prot

P05089

Related

ENSP00000349446.2, ENST00000356962.2

Conserved Domains (1) summary

cd11587
Location:9 → 311

Arginase-like; Arginase types I and II and arginase-like family
NM_001369020.1 → NP_001355949.1 arginase-1 isoform 3

Status: REVIEWED

Source sequence(s)

AL121575

RNA

NR_160934.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AL121575

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p12 Primary Assembly

Range

131573159..131584332

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011535801.2 → XP_011534103.1 arginase-1 isoform X1

Conserved Domains (1) summary

cl17011
Location:9 → 218

Arginase_HDAC; Arginase-like and histone-like hydrolases