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Protein

Arginase-2, mitochondrial

Gene

ARG2

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

Functioni

May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4+ and CD8+ T cells (PubMed:27745970). May suppress inflammation-related signaling in asthmatic airway epithelium (PubMed:27214549). May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism (By similarity). In fetal dendritic cells may play a role in promoting immune suppression and T cell TNF-alpha production during gestation (PubMed:28614294). Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction (PubMed:22928666). Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling (PubMed:25484082). Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity (PubMed:23832324). Since NOS is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase-2 plays a role in both male and female sexual arousal (PubMed:12859189).By similarity6 Publications

Catalytic activityi

L-arginine + H2O = L-ornithine + urea.1 Publication

Cofactori

Mn2+PROSITE-ProRule annotation1 PublicationNote: Binds 2 manganese ions per subunit.PROSITE-ProRule annotation1 Publication

Pathwayi: urea cycle

This protein is involved in step 1 of the subpathway that synthesizes L-ornithine and urea from L-arginine.By similarity
Proteins known to be involved in this subpathway in this organism are:
  1. Arginase-2, mitochondrial (ARG2), Arginase-1 (ARG1), Arginase (ARG2)
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 bindingi120Manganese 1Combined sources1 Publication1
Metal bindingi143Manganese 1Combined sources1 Publication1
Metal bindingi143Manganese 2Combined sources1 Publication1
Metal bindingi145Manganese 2Combined sources1 Publication1
Metal bindingi147Manganese 1Combined sources1 Publication1
Binding sitei202SubstrateCombined sources1 Publication1
Metal bindingi251Manganese 1Combined sources1 Publication1
Metal bindingi251Manganese 2Combined sources1 Publication1
Metal bindingi253Manganese 2Combined sources1 Publication1
Binding sitei265SubstrateBy similarity1
Binding sitei296SubstrateCombined sources1 Publication1

GO - Molecular functioni

  • arginase activity Source: CACAO
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BioCyciMetaCyc:HS01388-MONOMER
BRENDAi3.5.3.1 2681
ReactomeiR-HSA-70635 Urea cycle
SABIO-RKiP78540
SIGNORiP78540
UniPathwayi
UPA00158;UER00270

Names & Taxonomyi

Protein namesi
Recommended name:
Arginase-2, mitochondrial (EC:3.5.3.11 Publication)
Alternative name(s):
Arginase II
Kidney-type arginase
Non-hepatic arginase
Type II arginase
Gene namesi
Name:ARG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000081181.7
HGNCiHGNC:664 ARG2
MIMi107830 gene
neXtProtiNX_P78540

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

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi384
OpenTargetsiENSG00000081181
PharmGKBiPA24948

Chemistry databases

ChEMBLiCHEMBL1795148
DrugBankiDB00125 L-Arginine
DB00129 L-Ornithine
DB03731 S-2-(Boronoethyl)-L-Cysteine
GuidetoPHARMACOLOGYi1245

Polymorphism and mutation databases

BioMutaiARG2
DMDMi2492935

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 22MitochondrionSequence analysisAdd BLAST22
ChainiPRO_000000208423 – 354Arginase-2, mitochondrialAdd BLAST332

Proteomic databases

EPDiP78540
MaxQBiP78540
PaxDbiP78540
PeptideAtlasiP78540
PRIDEiP78540
ProteomicsDBi57644

PTM databases

iPTMnetiP78540
PhosphoSitePlusiP78540

Expressioni

Tissue specificityi

Expressed most strongly in kidney and prostate, much less strongly in the brain, skeletal muscle, placenta, lung, mammary gland, macrophage, uterus, testis and gut, but apparently not in the liver, heart and pancreas. Expressed in activated T cells (PubMed:27745970).1 Publication

Gene expression databases

BgeeiENSG00000081181 Expressed in 199 organ(s), highest expression level in tendon
CleanExiHS_ARG2
ExpressionAtlasiP78540 baseline and differential
GenevisibleiP78540 HS

Organism-specific databases

HPAiCAB009435
HPA000663

Interactioni

Subunit structurei

Homotrimer.1 Publication

Protein-protein interaction databases

BioGridi106879, 6 interactors
IntActiP78540, 2 interactors
MINTiP78540
STRINGi9606.ENSP00000261783

Chemistry databases

BindingDBiP78540

Structurei

Secondary structure

1354
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP78540
SMRiP78540
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP78540

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni145 – 149Substrate bindingCombined sources1 Publication5
Regioni156 – 158Substrate bindingCombined sources1 Publication3

Sequence similaritiesi

Belongs to the arginase family.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2965 Eukaryota
COG0010 LUCA
GeneTreeiENSGT00530000063082
HOGENOMiHOG000204319
HOVERGENiHBG003030
InParanoidiP78540
KOiK01476
OMAiSAVARHC
OrthoDBiEOG091G0A38
PhylomeDBiP78540
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

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P78540-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSLRGSLSRL LQTRVHSILK KSVHSVAVIG APFSQGQKRK GVEHGPAAIR
60 70 80 90 100
EAGLMKRLSS LGCHLKDFGD LSFTPVPKDD LYNNLIVNPR SVGLANQELA
110 120 130 140 150
EVVSRAVSDG YSCVTLGGDH SLAIGTISGH ARHCPDLCVV WVDAHADINT
160 170 180 190 200
PLTTSSGNLH GQPVSFLLRE LQDKVPQLPG FSWIKPCISS ASIVYIGLRD
210 220 230 240 250
VDPPEHFILK NYDIQYFSMR DIDRLGIQKV MERTFDLLIG KRQRPIHLSF
260 270 280 290 300
DIDAFDPTLA PATGTPVVGG LTYREGMYIA EEIHNTGLLS ALDLVEVNPQ
310 320 330 340 350
LATSEEEAKT TANLAVDVIA SSFGQTREGG HIVYDQLPTP SSPDESENQA

RVRI
Length:354
Mass (Da):38,578
Last modified:May 1, 1997 - v1
Checksum:i1624FAC7D515C68B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033520240G → R. Corresponds to variant dbSNP:rs17104534Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86724 mRNA Translation: BAA13158.1
U75667 mRNA Translation: AAB39855.1
U82256 mRNA Translation: AAC51664.1
AY074489 mRNA Translation: AAL71548.1
CR536550 mRNA Translation: CAG38787.1
AK312484 mRNA Translation: BAG35387.1
CH471061 Genomic DNA Translation: EAW80943.1
BC001350 mRNA Translation: AAH01350.1
BC008464 mRNA Translation: AAH08464.1
BC029050 mRNA Translation: AAH29050.1
CCDSiCCDS9785.1
RefSeqiNP_001163.1, NM_001172.3
UniGeneiHs.226007

Genome annotation databases

EnsembliENST00000261783; ENSP00000261783; ENSG00000081181
GeneIDi384
KEGGihsa:384
UCSCiuc001xjs.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Arginase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D86724 mRNA Translation: BAA13158.1
U75667 mRNA Translation: AAB39855.1
U82256 mRNA Translation: AAC51664.1
AY074489 mRNA Translation: AAL71548.1
CR536550 mRNA Translation: CAG38787.1
AK312484 mRNA Translation: BAG35387.1
CH471061 Genomic DNA Translation: EAW80943.1
BC001350 mRNA Translation: AAH01350.1
BC008464 mRNA Translation: AAH08464.1
BC029050 mRNA Translation: AAH29050.1
CCDSiCCDS9785.1
RefSeqiNP_001163.1, NM_001172.3
UniGeneiHs.226007

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PQ3X-ray2.70A/B/C/D/E/F24-329[»]
4HZEX-ray1.60A/B/C24-329[»]
4I06X-ray1.80A/B/C24-329[»]
4IE2X-ray2.21A/B/C24-329[»]
4IE3X-ray2.35A/B/C24-329[»]
4IXUX-ray1.90A/B/C24-329[»]
4IXVX-ray2.30A/B/C24-329[»]
ProteinModelPortaliP78540
SMRiP78540
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106879, 6 interactors
IntActiP78540, 2 interactors
MINTiP78540
STRINGi9606.ENSP00000261783

Chemistry databases

BindingDBiP78540
ChEMBLiCHEMBL1795148
DrugBankiDB00125 L-Arginine
DB00129 L-Ornithine
DB03731 S-2-(Boronoethyl)-L-Cysteine
GuidetoPHARMACOLOGYi1245

PTM databases

iPTMnetiP78540
PhosphoSitePlusiP78540

Polymorphism and mutation databases

BioMutaiARG2
DMDMi2492935

Proteomic databases

EPDiP78540
MaxQBiP78540
PaxDbiP78540
PeptideAtlasiP78540
PRIDEiP78540
ProteomicsDBi57644

Protocols and materials databases

DNASUi384
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261783; ENSP00000261783; ENSG00000081181
GeneIDi384
KEGGihsa:384
UCSCiuc001xjs.4 human

Organism-specific databases

CTDi384
DisGeNETi384
EuPathDBiHostDB:ENSG00000081181.7
GeneCardsiARG2
HGNCiHGNC:664 ARG2
HPAiCAB009435
HPA000663
MIMi107830 gene
neXtProtiNX_P78540
OpenTargetsiENSG00000081181
PharmGKBiPA24948
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2965 Eukaryota
COG0010 LUCA
GeneTreeiENSGT00530000063082
HOGENOMiHOG000204319
HOVERGENiHBG003030
InParanoidiP78540
KOiK01476
OMAiSAVARHC
OrthoDBiEOG091G0A38
PhylomeDBiP78540
TreeFamiTF300034

Enzyme and pathway databases

UniPathwayi
UPA00158;UER00270

BioCyciMetaCyc:HS01388-MONOMER
BRENDAi3.5.3.1 2681
ReactomeiR-HSA-70635 Urea cycle
SABIO-RKiP78540
SIGNORiP78540

Miscellaneous databases

ChiTaRSiARG2 human
EvolutionaryTraceiP78540
GenomeRNAii384
PROiPR:P78540
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000081181 Expressed in 199 organ(s), highest expression level in tendon
CleanExiHS_ARG2
ExpressionAtlasiP78540 baseline and differential
GenevisibleiP78540 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiARGI2_HUMAN
AccessioniPrimary (citable) accession number: P78540
Secondary accession number(s): B2R690, Q6FHY8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: September 12, 2018
This is version 170 of the entry and version 1 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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