ARGI2_RAT
ID ARGI2_RAT Reviewed; 354 AA.
AC O08701; P97539;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 143.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; 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] OF 87-168.
RC STRAIN=Wistar; TISSUE=Small intestine;
RX PubMed=8898077; DOI=10.1016/0014-5793(96)01015-0;
RA Gotoh T., Sonoki T., Nagasaki A., Terada K., Takiguchi M., Mori M.;
RT "Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase
RT II) and comparison of its induction with nitric oxide synthase in a murine
RT macrophage-like cell line.";
RL FEBS Lett. 395:119-122(1996).
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 T
CC cells. May suppress inflammation-related signaling in asthmatic airway
CC epithelium. May play a role in promoting prenatal immune suppression.
CC Regulates RPS6KB1 signaling, which promotes endothelial cell senescence
CC and inflammation and implicates NOS3/eNOS dysfunction. Can inhibit
CC endothelial autophagy independently of its enzymatic activity
CC implicating mTORC2 signaling. Involved in vascular smooth muscle cell
CC senescence and apoptosis independently of its enzymatic activity.
CC {ECO:0000250|UniProtKB:O08691, ECO:0000250|UniProtKB:P78540}.
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 -!- INTERACTION:
CC O08701; P29476: Nos1; NbExp=2; IntAct=EBI-15573788, EBI-349460;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:O08691,
CC ECO:0000250|UniProtKB:P78540}.
CC -!- SIMILARITY: Belongs to the arginase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00742}.
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DR EMBL; U90887; AAC22580.1; -; mRNA.
DR EMBL; D86928; BAA13183.1; -; mRNA.
DR RefSeq; NP_062041.1; NM_019168.1.
DR AlphaFoldDB; O08701; -.
DR SMR; O08701; -.
DR DIP; DIP-61133N; -.
DR IntAct; O08701; 1.
DR STRING; 10116.ENSRNOP00000015083; -.
DR PaxDb; O08701; -.
DR PRIDE; O08701; -.
DR GeneID; 29215; -.
DR KEGG; rno:29215; -.
DR UCSC; RGD:2151; rat.
DR CTD; 384; -.
DR RGD; 2151; Arg2.
DR eggNOG; KOG2965; Eukaryota.
DR InParanoid; O08701; -.
DR OrthoDB; 1179130at2759; -.
DR PhylomeDB; O08701; -.
DR BRENDA; 3.5.3.1; 5301.
DR Reactome; R-RNO-70635; Urea cycle.
DR SABIO-RK; O08701; -.
DR UniPathway; UPA00158; UER00270.
DR PRO; PR:O08701; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0004053; F:arginase activity; IDA:RGD.
DR GO; GO:0030145; F:manganese ion binding; IBA:GO_Central.
DR GO; GO:0050998; F:nitric-oxide synthase binding; IPI:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEP:RGD.
DR GO; GO:0019547; P:arginine catabolic process to ornithine; IDA:RGD.
DR GO; GO:0006525; P:arginine metabolic process; IMP:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0071353; P:cellular response to interleukin-4; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR GO; GO:0007494; P:midgut development; IEP:RGD.
DR GO; GO:1905403; P:negative regulation of activated CD8-positive, alpha-beta T cell apoptotic process; ISO:RGD.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; ISO:RGD.
DR GO; GO:0071644; P:negative regulation of chemokine (C-C motif) ligand 4 production; ISO:RGD.
DR GO; GO:0071650; P:negative regulation of chemokine (C-C motif) ligand 5 production; ISO:RGD.
DR GO; GO:1900425; P:negative regulation of defense response to bacterium; ISO:RGD.
DR GO; GO:0032696; P:negative regulation of interleukin-13 production; ISO:RGD.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0071641; P:negative regulation of macrophage inflammatory protein 1 alpha production; ISO:RGD.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IMP:RGD.
DR GO; GO:0045988; P:negative regulation of striated muscle contraction; IMP:RGD.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0002829; P:negative regulation of type 2 immune response; ISO:RGD.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISO:RGD.
DR GO; GO:0032651; P:regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:1905541; P:regulation of L-arginine import across plasma membrane; IDA:RGD.
DR GO; GO:0045428; P:regulation of nitric oxide biosynthetic process; IEP:RGD.
DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR GO; GO:0014075; P:response to amine; IEP:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0048678; P:response to axon injury; IEP:RGD.
DR GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0009635; P:response to herbicide; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0046689; P:response to mercury ion; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0010269; P:response to selenium ion; IEP:RGD.
DR GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0006941; P:striated muscle contraction; ISO:RGD.
DR GO; GO:0000050; P:urea cycle; IEA:UniProtKB-UniPathway.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
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; Hydrolase; Immunity;
KW Innate immunity; Manganese; Metal-binding; Mitochondrion;
KW 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_0000002086"
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 CONFLICT 88
FT /note="Y -> N (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="R -> P (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="A -> S (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="L -> M (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="D -> Y (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="S -> I (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="D -> Y (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="L -> V (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="I -> L (in Ref. 2; BAA13183)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 354 AA; 38640 MW; BC03E6BC99B29B8C CRC64;
MFLRSSVSRL LHGQIPCALT RSVHSVAVVG APFSRGQKKK GVEYGPAAIR EAGLLKRLSM
LGCHIKDFGD LSFTNVPKDD PYNNLVVYPR SVGIANQELA EVVSRAVSGG YSCVTLGGDH
SLAIGTISGH ARHHPDLCVI WVDAHADINT PLTTVSGNIH GQPLSFLIRE LQDKVPQLPG
FSWIKPCLSP PNLVYIGLRD VEPAEHFILK SFDIQYFSMR DIDRLGIQKV MEQTFDRLIG
KRKRPIHLSF DIDAFDPKLA PATGTPVVGG LTYREGLYIT EEIHSTGLLS ALDLVEVNPH
LATSEEEAKA TASLAVDVIA SSFGQTREGG HIAYDHLPTP SSPHESEKEE CVRI
