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 27-MAR-2024, entry version 176. 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; Evidence={ECO:0000255|PROSITE- CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000021550; -. DR PeptideAtlas; O08691; -. DR ProteomicsDB; 296415; -. DR Antibodypedia; 1; 502 antibodies from 36 providers. DR DNASU; 11847; -. DR Ensembl; ENSMUST00000021550.7; ENSMUSP00000021550.7; ENSMUSG00000021125.7. DR GeneID; 11847; -. DR KEGG; mmu:11847; -. DR UCSC; uc007nzv.2; mouse. DR AGR; MGI:1330806; -. 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; YKEFRYA; -. DR OrthoDB; 161483at2759; -. DR PhylomeDB; O08691; -. DR TreeFam; TF300034; -. DR Reactome; R-MMU-70635; Urea cycle. DR UniPathway; UPA00158; UER00270. DR BioGRID-ORCS; 11847; 1 hit in 78 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 194 other cell types or tissues. 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: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 Gene3D; 3.40.800.10; Ureohydrolase domain; 1. DR InterPro; IPR014033; Arginase. DR InterPro; IPR006035; Ureohydrolase. DR InterPro; IPR023696; Ureohydrolase_dom_sf. DR InterPro; IPR020855; Ureohydrolase_Mn_BS. DR NCBIfam; TIGR01229; rocF_arginase; 1. DR PANTHER; PTHR43782; ARGINASE; 1. DR PANTHER; PTHR43782:SF4; ARGINASE-2, MITOCHONDRIAL; 1. DR Pfam; PF00491; Arginase; 1. DR PIRSF; PIRSF036979; Arginase; 1. DR PRINTS; PR00116; ARGINASE. DR SUPFAM; SSF52768; Arginase/deacetylase; 1. DR PROSITE; PS01053; ARGINASE_1; 1. DR PROSITE; PS51409; ARGINASE_2; 1. DR Genevisible; O08691; MM. 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 //