ARGI2_MOUSE
ID ARGI2_MOUSE Reviewed; 354 AA.
AC O08691;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Arginase-2, mitochondrial;
DE EC=3.5.3.1 {ECO:0000250|UniProtKB:P05089};
DE AltName: Full=Arginase II;
DE AltName: Full=Kidney-type arginase;
DE AltName: Full=Non-hepatic arginase;
DE AltName: Full=Type II arginase;
DE Flags: Precursor;
GN Name=Arg2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=9608538; DOI=10.1006/mgme.1997.2669;
RA Iyer R.K., Bando J.M., Jenkinson C.P., Vockley J.G., Kim P.S., Kern R.M.,
RA Cederbaum S.D., Grody W.W.;
RT "Cloning and characterization of the mouse and rat type II arginase
RT genes.";
RL Mol. Genet. Metab. 63:168-175(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=9814991; DOI=10.1152/ajpendo.1998.275.5.e740;
RA Morris S.M. Jr., Kepka-Lenhart D., Chen L.C.;
RT "Differential regulation of arginases and inducible nitric oxide synthase
RT in murine macrophage cells.";
RL Am. J. Physiol. 275:E740-E747(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=9745037; DOI=10.1007/s003359900874;
RA Shi O.U., Kepka-Lenhart D., Morris S.M. Jr., O'Brien W.E.;
RT "Structure of the murine arginase II gene.";
RL Mamm. Genome 9:822-824(1998).
RN [4]
RP PROTEIN SEQUENCE OF 51-57, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF HIS-160.
RX PubMed=22928666; DOI=10.1111/acel.12001;
RA Yepuri G., Velagapudi S., Xiong Y., Rajapakse A.G., Montani J.P.,
RA Ming X.F., Yang Z.;
RT "Positive crosstalk between arginase-II and S6K1 in vascular endothelial
RT inflammation and aging.";
RL Aging Cell 11:1005-1016(2012).
RN [7]
RP FUNCTION.
RX PubMed=25484082; DOI=10.4161/15548627.2014.981789;
RA Xiong Y., Yepuri G., Forbiteh M., Yu Y., Montani J.P., Yang Z., Ming X.F.;
RT "ARG2 impairs endothelial autophagy through regulation of MTOR and
RT PRKAA/AMPK signaling in advanced atherosclerosis.";
RL Autophagy 10:2223-2238(2014).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25009204; DOI=10.4049/jimmunol.1301913;
RA Dunand-Sauthier I., Irla M., Carnesecchi S., Seguin-Estevez Q.,
RA Vejnar C.E., Zdobnov E.M., Santiago-Raber M.L., Reith W.;
RT "Repression of arginase-2 expression in dendritic cells by microRNA-155 is
RT critical for promoting T cell proliferation.";
RL J. Immunol. 193:1690-1700(2014).
RN [9]
RP FUNCTION.
RX PubMed=27074721; DOI=10.1007/s00726-016-2231-2;
RA Hardbower D.M., Asim M., Murray-Stewart T., Casero R.A. Jr., Verriere T.,
RA Lewis N.D., Chaturvedi R., Piazuelo M.B., Wilson K.T.;
RT "Arginase 2 deletion leads to enhanced M1 macrophage activation and
RT upregulated polyamine metabolism in response to Helicobacter pylori
RT infection.";
RL Amino Acids 48:2375-2388(2016).
RN [10]
RP FUNCTION.
RX PubMed=27745970; DOI=10.1016/j.cell.2016.09.031;
RA Geiger R., Rieckmann J.C., Wolf T., Basso C., Feng Y., Fuhrer T.,
RA Kogadeeva M., Picotti P., Meissner F., Mann M., Zamboni N., Sallusto F.,
RA Lanzavecchia A.;
RT "L-arginine modulates T cell metabolism and enhances survival and anti-
RT tumor activity.";
RL Cell 167:829-842(2016).
RN [11]
RP FUNCTION.
RX PubMed=27214549; DOI=10.1172/jci82925;
RA Xu W., Ghosh S., Comhair S.A., Asosingh K., Janocha A.J., Mavrakis D.A.,
RA Bennett C.D., Gruca L.L., Graham B.B., Queisser K.A., Kao C.C., Wedes S.H.,
RA Petrich J.M., Tuder R.M., Kalhan S.C., Erzurum S.C.;
RT "Increased mitochondrial arginine metabolism supports bioenergetics in
RT asthma.";
RL J. Clin. Invest. 126:2465-2481(2016).
CC -!- FUNCTION: May play a role in the regulation of extra-urea cycle
CC arginine metabolism and also in down-regulation of nitric oxide
CC synthesis. Extrahepatic arginase functions to regulate L-arginine
CC bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a
CC critical regulator of innate and adaptive immune responses. Seems to be
CC involved in negative regulation of the survival capacity of activated
CC CD4(+) and CD8(+) T cells (PubMed:27745970, PubMed:25009204). May
CC suppress inflammation-related signaling in asthmatic airway epithelium
CC (PubMed:27214549). May contribute to the immune evasion of H.pylori by
CC restricting M1 macrophage activation and polyamine metabolism
CC (PubMed:27074721). May play a role in promoting prenatal immune
CC suppression (By similarity). Regulates RPS6KB1 signaling, which
CC promotes endothelial cell senescence and inflammation and implicates
CC NOS3/eNOS dysfunction (PubMed:22928666). Can inhibit endothelial
CC autophagy independently of its enzymatic activity implicating mTORC2
CC signaling (PubMed:25484082). Involved in vascular smooth muscle cell
CC senescence and apoptosis independently of its enzymatic activity (By
CC similarity). {ECO:0000250|UniProtKB:P78540,
CC ECO:0000269|PubMed:22928666, ECO:0000269|PubMed:25009204,
CC ECO:0000269|PubMed:25484082, ECO:0000269|PubMed:27074721,
CC ECO:0000269|PubMed:27214549, ECO:0000269|PubMed:27745970}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-arginine = L-ornithine + urea; Xref=Rhea:RHEA:20569,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16199, ChEBI:CHEBI:32682,
CC ChEBI:CHEBI:46911; EC=3.5.3.1;
CC Evidence={ECO:0000250|UniProtKB:P05089};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00742};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00742};
CC -!- PATHWAY: Nitrogen metabolism; urea cycle; L-ornithine and urea from L-
CC arginine: step 1/1. {ECO:0000250|UniProtKB:P05089}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:P78540}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:25009204}.
CC -!- SIMILARITY: Belongs to the arginase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00742}.
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DR EMBL; U90886; AAC22548.1; -; mRNA.
DR EMBL; AF032466; AAB86959.1; -; mRNA.
DR EMBL; AF045965; AAC78460.1; -; Genomic_DNA.
DR EMBL; AF044680; AAC78460.1; JOINED; Genomic_DNA.
DR EMBL; AF045959; AAC78460.1; JOINED; Genomic_DNA.
DR EMBL; AF045960; AAC78460.1; JOINED; Genomic_DNA.
DR EMBL; AF045961; AAC78460.1; JOINED; Genomic_DNA.
DR EMBL; AF045962; AAC78460.1; JOINED; Genomic_DNA.
DR EMBL; AF045963; AAC78460.1; JOINED; Genomic_DNA.
DR EMBL; AF045964; AAC78460.1; JOINED; Genomic_DNA.
DR CCDS; CCDS26007.1; -.
DR RefSeq; NP_033835.1; NM_009705.3.
DR AlphaFoldDB; O08691; -.
DR SMR; O08691; -.
DR BioGRID; 198191; 1.
DR STRING; 10090.ENSMUSP00000021550; -.
DR iPTMnet; O08691; -.
DR PhosphoSitePlus; O08691; -.
DR REPRODUCTION-2DPAGE; O08691; -.
DR MaxQB; O08691; -.
DR PaxDb; O08691; -.
DR PeptideAtlas; O08691; -.
DR PRIDE; O08691; -.
DR ProteomicsDB; 296415; -.
DR Antibodypedia; 1; 438 antibodies from 36 providers.
DR DNASU; 11847; -.
DR Ensembl; ENSMUST00000021550; ENSMUSP00000021550; ENSMUSG00000021125.
DR GeneID; 11847; -.
DR KEGG; mmu:11847; -.
DR UCSC; uc007nzv.2; mouse.
DR CTD; 384; -.
DR MGI; MGI:1330806; Arg2.
DR VEuPathDB; HostDB:ENSMUSG00000021125; -.
DR eggNOG; KOG2965; Eukaryota.
DR GeneTree; ENSGT00950000183195; -.
DR HOGENOM; CLU_039478_6_0_1; -.
DR InParanoid; O08691; -.
DR OMA; IATCFGQ; -.
DR OrthoDB; 1179130at2759; -.
DR PhylomeDB; O08691; -.
DR TreeFam; TF300034; -.
DR Reactome; R-MMU-70635; Urea cycle.
DR UniPathway; UPA00158; UER00270.
DR BioGRID-ORCS; 11847; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Arg2; mouse.
DR PRO; PR:O08691; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; O08691; protein.
DR Bgee; ENSMUSG00000021125; Expressed in small intestine Peyer's patch and 191 other tissues.
DR Genevisible; O08691; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004053; F:arginase activity; ISO:MGI.
DR GO; GO:0030145; F:manganese ion binding; IBA:GO_Central.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0019547; P:arginine catabolic process to ornithine; ISO:MGI.
DR GO; GO:0006525; P:arginine metabolic process; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1905403; P:negative regulation of activated CD8-positive, alpha-beta T cell apoptotic process; IMP:UniProtKB.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IMP:UniProtKB.
DR GO; GO:0071644; P:negative regulation of chemokine (C-C motif) ligand 4 production; IMP:UniProtKB.
DR GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; IMP:UniProtKB.
DR GO; GO:1900425; P:negative regulation of defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0032696; P:negative regulation of interleukin-13 production; IMP:UniProtKB.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:UniProtKB.
DR GO; GO:0071641; P:negative regulation of macrophage inflammatory protein 1 alpha production; IMP:UniProtKB.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0045988; P:negative regulation of striated muscle contraction; ISO:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0002829; P:negative regulation of type 2 immune response; IMP:UniProtKB.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISO:MGI.
DR GO; GO:0032651; P:regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:1905541; P:regulation of L-arginine import across plasma membrane; ISO:MGI.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006941; P:striated muscle contraction; IMP:MGI.
DR GO; GO:0000050; P:urea cycle; IEA:UniProtKB-UniPathway.
DR GO; GO:0001657; P:ureteric bud development; IEP:UniProtKB.
DR CDD; cd09989; Arginase; 1.
DR InterPro; IPR014033; Arginase.
DR InterPro; IPR006035; Ureohydrolase.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR InterPro; IPR020855; Ureohydrolase_Mn_BS.
DR PANTHER; PTHR43782; PTHR43782; 1.
DR Pfam; PF00491; Arginase; 1.
DR PIRSF; PIRSF036979; Arginase; 1.
DR PRINTS; PR00116; ARGINASE.
DR SUPFAM; SSF52768; SSF52768; 1.
DR TIGRFAMs; TIGR01229; rocF_arginase; 1.
DR PROSITE; PS01053; ARGINASE_1; 1.
DR PROSITE; PS51409; ARGINASE_2; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Arginine metabolism; Direct protein sequencing;
KW Hydrolase; Immunity; Innate immunity; Manganese; Metal-binding;
KW Mitochondrion; Reference proteome; Transit peptide; Urea cycle.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 23..354
FT /note="Arginase-2, mitochondrial"
FT /id="PRO_0000002085"
FT BINDING 120
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 143
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 143
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 145..149
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P05089"
FT BINDING 145
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 147
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 156..158
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P05089"
FT BINDING 202
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 251
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 251
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 253
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00742"
FT BINDING 265
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P53608"
FT BINDING 296
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P78540"
FT MUTAGEN 160
FT /note="H->F: Catalytically inactive; defective in promoting
FT NOS3/eNOS-uncoupling in endothelial cells."
SQ SEQUENCE 354 AA; 38878 MW; B372DF68A19473F2 CRC64;
MFLRSSASRL LHGQIPCVLT RSVHSVAIVG APFSRGQKKL GVEYGPAAIR EAGLLKRLSR
LGCHLKDFGD LSFTNVPQDD PYNNLVVYPR SVGLANQELA EVVSRAVSGG YSCVTMGGDH
SLAIGTIIGH ARHRPDLCVI WVDAHADINT PLTTVSGNIH GQPLSFLIKE LQDKVPQLPG
FSWIKPCLSP PNIVYIGLRD VEPPEHFILK NYDIQYFSMR EIDRLGIQKV MEQTFDRLIG
KRQRPIHLSF DIDAFDPKLA PATGTPVVGG LTYREGVYIT EEIHNTGLLS ALDLVEVNPH
LATSEEEAKA TARLAVDVIA SSFGQTREGG HIVYDHLPTP SSPHESENEE CVRI
