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Protein

Arginase-1

Gene

ARG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.Curated
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.By similarity3 Publications

Catalytic activityi

L-arginine + H2O = L-ornithine + urea.2 Publications

Cofactori

Mn2+4 PublicationsNote: Binds 2 manganese ions per subunit.4 Publications

Pathwayi: urea cycle

This protein is involved in step 1 of the subpathway that synthesizes L-ornithine and urea from L-arginine.1 Publication
Proteins known to be involved in this subpathway in this organism are:
  1. Arginase (ARG2), Arginase-2, mitochondrial (ARG2), Arginase-1 (ARG1)
This subpathway is part of the pathway urea cycle, which is itself part of Nitrogen metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-ornithine and urea from L-arginine, the pathway urea cycle and in Nitrogen metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi101Manganese 1Combined sources4 Publications1
Metal bindingi124Manganese 1Combined sources4 Publications1
Metal bindingi124Manganese 2Combined sources4 Publications1
Metal bindingi126Manganese 2Combined sources4 Publications1
Metal bindingi128Manganese 1Combined sources4 Publications1
Binding sitei183SubstrateCombined sources1
Metal bindingi232Manganese 1Combined sources4 Publications1
Metal bindingi232Manganese 2Combined sources4 Publications1
Metal bindingi234Manganese 2Combined sources4 Publications1
Binding sitei246SubstrateBy similarity1
Binding sitei277SubstrateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processAdaptive immunity, Arginine metabolism, Immunity, Innate immunity, Urea cycle
LigandManganese, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS04231-MONOMER
BRENDAi3.5.3.1 2681
ReactomeiR-HSA-6798695 Neutrophil degranulation
R-HSA-70635 Urea cycle
SABIO-RKiP05089
SIGNORiP05089
UniPathwayiUPA00158; UER00270

Names & Taxonomyi

Protein namesi
Recommended name:
Arginase-1 (EC:3.5.3.12 Publications)
Alternative name(s):
Liver-type arginase
Type I arginase
Gene namesi
Name:ARG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000118520.13
HGNCiHGNC:663 ARG1
MIMi608313 gene
neXtProtiNX_P05089

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Argininemia (ARGIN)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia and progressive spastic quadriplegia.
See also OMIM:207800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01559411I → T in ARGIN; 12% of wild-type activity. 2 PublicationsCorresponds to variant dbSNP:rs28941474EnsemblClinVar.1
Natural variantiVAR_07216427G → D in ARGIN; 5.2% of wild-type activity. 1 Publication1
Natural variantiVAR_07216574G → V in ARGIN; 9.3% of wild-type activity. 1 Publication1
Natural variantiVAR_072166125A → V in ARGIN; decreases erythrocyte arginase activity. 1 Publication1
Natural variantiVAR_072167134T → I in ARGIN; 9.3% of wild-type activity. 1 Publication1
Natural variantiVAR_015595138G → V in ARGIN. 1 PublicationCorresponds to variant dbSNP:rs104893943EnsemblClinVar.1
Natural variantiVAR_072168180R → T in ARGIN; decreases erythrocyte arginase activity. 1 Publication1
Natural variantiVAR_000674235G → R in ARGIN; decreases erythrocyte arginase activity. 2 PublicationsCorresponds to variant dbSNP:rs104893948EnsemblClinVar.1
Natural variantiVAR_072169308R → Q in ARGIN; 20.8% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs377280518Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi383
GeneReviewsiARG1
MalaCardsiARG1
MIMi207800 phenotype
OpenTargetsiENSG00000118520
Orphaneti90 Argininemia
PharmGKBiPA24947

Chemistry databases

ChEMBLiCHEMBL1075097
DrugBankiDB01983 2(S)-Amino-6-Boronohexanoic Acid
DB04585 DEHYDRO-2(S)-AMINO-6-BORONOHEXANOIC ACID
DB04197 Descarboxy-nor-N(Omega)-Hydroxy-L-Arginine
DB02499 Dinor-N(Omega)-Hydroxy-L-Arginine
DB00129 L-Ornithine
DB03144 N-Omega-Hydroxy-L-Arginine
DB02381 Nor-N-Omega-Hydroxy-L-Arginine
DB03731 S-2-(Boronoethyl)-L-Cysteine
DB04648 S-propylamine-L-cysteine
DB02689 S-{2-[Amino(Dihydroxy)-Lambda~4~-Sulfanyl]Ethyl}-D-Cysteine
DB03904 Urea
GuidetoPHARMACOLOGYi1244

Polymorphism and mutation databases

BioMutaiARG1
DMDMi12230985

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001736931 – 322Arginase-1Add BLAST322

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei17N6-succinyllysineBy similarity1
Modified residuei62PhosphoserineCombined sources1
Modified residuei72PhosphoserineBy similarity1
Modified residuei75N6-succinyllysineBy similarity1
Modified residuei163PhosphoserineCombined sources1
Modified residuei217PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP05089
MaxQBiP05089
PaxDbiP05089
PeptideAtlasiP05089
PRIDEiP05089
ProteomicsDBi51784
51785 [P05089-2]
51786 [P05089-3]

PTM databases

iPTMnetiP05089
PhosphoSitePlusiP05089

Expressioni

Tissue specificityi

Within the immune system initially reported to be selectively expressed in granulocytes (polymorphonuclear leukocytes [PMNs]) (PubMed:15546957). Also detected in macrophages mycobacterial granulomas (PubMed:23749634). Expressed in group2 innate lymphoid cells (ILC2s) during lung disease (PubMed:27043409).2 Publications

Inductioni

By arginine or homoarginine.

Gene expression databases

BgeeiENSG00000118520
CleanExiHS_ARG1
GenevisibleiP05089 HS

Organism-specific databases

HPAiCAB009434
CAB056159
HPA003595
HPA024006

Interactioni

Subunit structurei

Homotrimer (PubMed:16141327, PubMed:17469833, PubMed:17562323, PubMed:18802628, PubMed:2241902). Interacts with CMTM6 (PubMed:28813417).6 Publications

Protein-protein interaction databases

BioGridi106878, 34 interactors
IntActiP05089, 14 interactors
MINTiP05089
STRINGi9606.ENSP00000357066

Chemistry databases

BindingDBiP05089

Structurei

Secondary structure

1322
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi7 – 13Combined sources7
Helixi22 – 26Combined sources5
Helixi27 – 33Combined sources7
Helixi36 – 42Combined sources7
Beta strandi46 – 52Combined sources7
Beta strandi67 – 69Combined sources3
Helixi70 – 89Combined sources20
Beta strandi93 – 99Combined sources7
Helixi101 – 103Combined sources3
Helixi104 – 114Combined sources11
Beta strandi119 – 126Combined sources8
Turni132 – 134Combined sources3
Helixi140 – 142Combined sources3
Helixi144 – 148Combined sources5
Helixi150 – 152Combined sources3
Turni153 – 155Combined sources3
Helixi171 – 173Combined sources3
Beta strandi174 – 179Combined sources6
Helixi184 – 193Combined sources10
Beta strandi196 – 199Combined sources4
Helixi200 – 206Combined sources7
Helixi208 – 220Combined sources13
Beta strandi221 – 223Combined sources3
Beta strandi227 – 232Combined sources6
Helixi233 – 235Combined sources3
Turni238 – 240Combined sources3
Beta strandi243 – 246Combined sources4
Helixi254 – 267Combined sources14
Beta strandi270 – 276Combined sources7
Helixi280 – 282Combined sources3
Helixi286 – 303Combined sources18

3D structure databases

ProteinModelPortaliP05089
SMRiP05089
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05089

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni126 – 130Substrate bindingCombined sources5
Regioni137 – 139Substrate bindingCombined sources3

Sequence similaritiesi

Belongs to the arginase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2965 Eukaryota
COG0010 LUCA
GeneTreeiENSGT00530000063082
HOGENOMiHOG000204319
HOVERGENiHBG003030
InParanoidiP05089
KOiK01476
OMAiEQECDVK
OrthoDBiEOG091G0A38
PhylomeDBiP05089
TreeFamiTF300034

Family and domain databases

InterProiView protein in InterPro
IPR014033 Arginase
IPR006035 Ureohydrolase
IPR023696 Ureohydrolase_dom_sf
IPR020855 Ureohydrolase_Mn_BS
PfamiView protein in Pfam
PF00491 Arginase, 1 hit
PIRSFiPIRSF036979 Arginase, 1 hit
PRINTSiPR00116 ARGINASE
SUPFAMiSSF52768 SSF52768, 1 hit
TIGRFAMsiTIGR01229 rocF_arginase, 1 hit
PROSITEiView protein in PROSITE
PS01053 ARGINASE_1, 1 hit
PS51409 ARGINASE_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P05089-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSAKSRTIGI IGAPFSKGQP RGGVEEGPTV LRKAGLLEKL KEQECDVKDY
60 70 80 90 100
GDLPFADIPN DSPFQIVKNP RSVGKASEQL AGKVAEVKKN GRISLVLGGD
110 120 130 140 150
HSLAIGSISG HARVHPDLGV IWVDAHTDIN TPLTTTSGNL HGQPVSFLLK
160 170 180 190 200
ELKGKIPDVP GFSWVTPCIS AKDIVYIGLR DVDPGEHYIL KTLGIKYFSM
210 220 230 240 250
TEVDRLGIGK VMEETLSYLL GRKKRPIHLS FDVDGLDPSF TPATGTPVVG
260 270 280 290 300
GLTYREGLYI TEEIYKTGLL SGLDIMEVNP SLGKTPEEVT RTVNTAVAIT
310 320
LACFGLAREG NHKPIDYLNP PK
Length:322
Mass (Da):34,735
Last modified:January 11, 2001 - v2
Checksum:i8F3BE2652243F622
GO
Isoform 2 (identifier: P05089-2) [UniParc]FASTAAdd to basket
Also known as: Erythroid variant

The sequence of this isoform differs from the canonical sequence as follows:
     43-43: Q → QVTQNFLIL

Note: May be due to a competing acceptor splice site. No experimental confirmation available.
Show »
Length:330
Mass (Da):35,664
Checksum:i3547D8B6C254179B
GO
Isoform 3 (identifier: P05089-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     204-289: Missing.

Show »
Length:236
Mass (Da):25,356
Checksum:i79F02C69B700AB67
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48K → E in AAL71547 (Ref. 3) Curated1
Sequence conflicti86E → Q in AAA51776 (PubMed:3540966).Curated1
Sequence conflicti202E → K in AAL71547 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01559411I → T in ARGIN; 12% of wild-type activity. 2 PublicationsCorresponds to variant dbSNP:rs28941474EnsemblClinVar.1
Natural variantiVAR_07216427G → D in ARGIN; 5.2% of wild-type activity. 1 Publication1
Natural variantiVAR_07216574G → V in ARGIN; 9.3% of wild-type activity. 1 Publication1
Natural variantiVAR_072166125A → V in ARGIN; decreases erythrocyte arginase activity. 1 Publication1
Natural variantiVAR_072167134T → I in ARGIN; 9.3% of wild-type activity. 1 Publication1
Natural variantiVAR_015595138G → V in ARGIN. 1 PublicationCorresponds to variant dbSNP:rs104893943EnsemblClinVar.1
Natural variantiVAR_072168180R → T in ARGIN; decreases erythrocyte arginase activity. 1 Publication1
Natural variantiVAR_000674235G → R in ARGIN; decreases erythrocyte arginase activity. 2 PublicationsCorresponds to variant dbSNP:rs104893948EnsemblClinVar.1
Natural variantiVAR_000675290T → S1 PublicationCorresponds to variant dbSNP:rs104893942EnsemblClinVar.1
Natural variantiVAR_072169308R → Q in ARGIN; 20.8% of wild-type activity. 1 PublicationCorresponds to variant dbSNP:rs377280518Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00933043Q → QVTQNFLIL in isoform 2. 1 Publication1
Alternative sequenceiVSP_009331204 – 289Missing in isoform 3. 2 PublicationsAdd BLAST86

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14502 mRNA Translation: AAA51776.1
X12662
, X12663, X12664, X12665, X12666, X12667, X12668, X12669 Genomic DNA Translation: CAA31188.1
AY074488 mRNA Translation: AAL71547.1
BT006741 mRNA Translation: AAP35387.1
AL121575 Genomic DNA Translation: CAB92071.1
AL121575 Genomic DNA Translation: CAI23317.1
AL121575 Genomic DNA Translation: CAI23318.1
BC005321 mRNA Translation: AAH05321.1
BC020653 mRNA Translation: AAH20653.1
CCDSiCCDS5145.1 [P05089-1]
CCDS59038.1 [P05089-2]
PIRiS02132 A26370
RefSeqiNP_000036.2, NM_000045.3 [P05089-1]
NP_001231367.1, NM_001244438.1 [P05089-2]
UniGeneiHs.440934

Genome annotation databases

EnsembliENST00000356962; ENSP00000349446; ENSG00000118520 [P05089-2]
ENST00000368087; ENSP00000357066; ENSG00000118520 [P05089-1]
ENST00000640973; ENSP00000492623; ENSG00000118520 [P05089-3]
GeneIDi383
KEGGihsa:383
UCSCiuc003qcp.3 human [P05089-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiARGI1_HUMAN
AccessioniPrimary (citable) accession number: P05089
Secondary accession number(s): A6NEA0
, Q5JWT5, Q5JWT6, Q8TE72, Q9BS50
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 11, 2001
Last modified: June 20, 2018
This is version 213 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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