ARGI1_RAT
ID ARGI1_RAT Reviewed; 323 AA.
AC P07824; Q5BK93;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Arginase-1;
DE EC=3.5.3.1 {ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:16266687};
DE AltName: Full=Liver-type arginase;
DE AltName: Full=Type I arginase;
GN Name=Arg1;
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 TISSUE=Liver;
RX PubMed=3571256; DOI=10.1016/s0021-9258(18)45565-2;
RA Kawamoto S., Amaya Y., Murakami K., Tokunaga F., Iwanaga S., Kobayashi K.,
RA Saheki T., Kimura S., Mori M.;
RT "Complete nucleotide sequence of cDNA and deduced amino acid sequence of
RT rat liver arginase.";
RL J. Biol. Chem. 262:6280-6283(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=2892837; DOI=10.1016/s0021-9258(18)69197-5;
RA Ohtake A., Takiguchi M., Shigeto Y., Amaya Y., Kawamoto S., Mori M.;
RT "Structural organization of the gene for rat liver-type arginase.";
RL J. Biol. Chem. 263:2245-2249(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP MUTAGENESIS OF GLY-235.
RX PubMed=11883902; DOI=10.1006/abbi.2001.2720;
RA Lavulo L.T., Emig F.A., Ash D.E.;
RT "Functional consequences of the G235R mutation in liver arginase leading to
RT hyperargininemia.";
RL Arch. Biochem. Biophys. 399:49-55(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND THR-281, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH MANGANESE.
RX PubMed=8849731; DOI=10.1038/383554a0;
RA Kanyo Z.F., Scolnick L.R., Ash D.E., Christianson D.W.;
RT "Structure of a unique binuclear manganese cluster in arginase.";
RL Nature 383:554-557(1996).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) IN COMPLEX WITH MANGANESE.
RX PubMed=9265637; DOI=10.1021/bi970800v;
RA Scolnick L.R., Kanyo Z.F., Cavalli R.C., Ash D.E., Christianson D.W.;
RT "Altering the binuclear manganese cluster of arginase diminishes
RT thermostability and catalytic function.";
RL Biochemistry 36:10558-10565(1997).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH MANGANESE, AND
RP CATALYTIC ACTIVITY.
RX PubMed=10542097; DOI=10.1038/14929;
RA Cox J.D., Kim N.N., Traish A.M., Christianson D.W.;
RT "Arginase-boronic acid complex highlights a physiological role in erectile
RT function.";
RL Nat. Struct. Biol. 6:1043-1047(1999).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 6-319 OF MUTANTS ASN-101; GLU-101;
RP ASN-128; GLU-128; ALA-232; CYS-232 AND GLU-234 IN COMPLEXES WITH MANGANESE
RP IONS, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF HIS-101;
RP ASP-128; ASP-232 AND ASP-234, AND CATALYTIC ACTIVITY.
RX PubMed=12820884; DOI=10.1021/bi030074y;
RA Cama E., Emig F.A., Ash D.E., Christianson D.W.;
RT "Structural and functional importance of first-shell metal ligands in the
RT binuclear manganese cluster of arginase I.";
RL Biochemistry 42:7748-7758(2003).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 6-319 IN COMPLEX WITH MANGANESE
RP IONS AND THE SYNTHETIC INHIBITOR (S)-2-AMINO-7-OXOHEPTANOIC ACID.
RX PubMed=15315440; DOI=10.1021/ja047788w;
RA Shin H., Cama E., Christianson D.W.;
RT "Design of amino acid aldehydes as transition-state analogue inhibitors of
RT arginase.";
RL J. Am. Chem. Soc. 126:10278-10284(2004).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 6-319 OF MUTANTS ALA-141; ASN-141;
RP ASP-141 AND CYS-141 IN COMPLEX WITH MANGANESE IONS, COFACTOR, MUTAGENESIS
RP OF HIS-141, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND
RP CATALYTIC ACTIVITY.
RX PubMed=16266687; DOI=10.1016/j.abb.2005.09.009;
RA Colleluori D.M., Reczkowski R.S., Emig F.A., Cama E., Cox J.D.,
RA Scolnick L.R., Compher K., Jude K., Han S., Viola R.E., Christianson D.W.,
RA Ash D.E.;
RT "Probing the role of the hyper-reactive histidine residue of arginase.";
RL Arch. Biochem. Biophys. 444:15-26(2005).
CC -!- FUNCTION: Key element of the urea cycle converting L-arginine to urea
CC and L-ornithine, which is further metabolized into metabolites proline
CC and polyamides that drive collagen synthesis and bioenergetic pathways
CC critical for cell proliferation, respectively; the urea cycle takes
CC place primarily in the liver and, to a lesser extent, in the kidneys.
CC {ECO:0000305}.
CC -!- FUNCTION: Functions in L-arginine homeostasis in nonhepatic tissues
CC characterized by the competition between nitric oxide synthase (NOS)
CC and arginase for the available intracellular substrate arginine.
CC Arginine metabolism is a critical regulator of innate and adaptive
CC immune responses. Involved in an antimicrobial effector pathway in
CC polymorphonuclear granulocytes (PMN). Upon PMN cell death is liberated
CC from the phagolysosome and depletes arginine in the microenvironment
CC leading to suppressed T cell and natural killer (NK) cell proliferation
CC and cytokine secretion (By similarity). In group 2 innate lymphoid
CC cells (ILC2s) promotes acute type 2 inflammation in the lung and is
CC involved in optimal ILC2 proliferation but not survival. Plays a role
CC in the immune response of alternatively activated or M2 macrophages in
CC processes such as wound healing and tissue regeneration, immune defense
CC against multicellular pathogens and parasites, and immune suppression
CC and allergic inflammation; the regulatory outcome seems to be organ
CC specific. In tumor-infiltrating dendritic cells (DCs) and myeloid-
CC derived suppressor cells (MDSCs) plays a role in suppression of T cell-
CC mediated antitumor immunity. {ECO:0000250|UniProtKB:P05089,
CC ECO:0000250|UniProtKB:Q61176}.
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; Evidence={ECO:0000269|PubMed:12820884,
CC ECO:0000269|PubMed:16266687};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00742,
CC ECO:0000269|PubMed:10542097, ECO:0000269|PubMed:12820884,
CC ECO:0000269|PubMed:15315440, ECO:0000269|PubMed:16266687,
CC ECO:0000269|PubMed:8849731, ECO:0000269|PubMed:9265637};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00742, ECO:0000269|PubMed:10542097,
CC ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
CC ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
CC ECO:0000269|PubMed:9265637};
CC -!- ACTIVITY REGULATION: Inactivated by diethyl pyrocarbonate (DEPC).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.4 mM for arginine {ECO:0000269|PubMed:12820884,
CC ECO:0000269|PubMed:16266687};
CC -!- PATHWAY: Nitrogen metabolism; urea cycle; L-ornithine and urea from L-
CC arginine: step 1/1. {ECO:0000250|UniProtKB:P05089}.
CC -!- SUBUNIT: Homotrimer (PubMed:15315440, PubMed:16266687). Interacts with
CC CMTM6 (By similarity). {ECO:0000250|UniProtKB:P05089,
CC ECO:0000269|PubMed:15315440, ECO:0000269|PubMed:16266687}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P05089}.
CC Cytoplasmic granule {ECO:0000250|UniProtKB:P05089}.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level).
CC {ECO:0000269|PubMed:16266687}.
CC -!- INDUCTION: By arginine or homoarginine.
CC -!- SIMILARITY: Belongs to the arginase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00742}.
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DR EMBL; J02720; AAA40761.1; -; mRNA.
DR EMBL; M17931; AAA40760.1; -; Genomic_DNA.
DR EMBL; M17924; AAA40760.1; JOINED; Genomic_DNA.
DR EMBL; M17925; AAA40760.1; JOINED; Genomic_DNA.
DR EMBL; M17926; AAA40760.1; JOINED; Genomic_DNA.
DR EMBL; M17927; AAA40760.1; JOINED; Genomic_DNA.
DR EMBL; M17928; AAA40760.1; JOINED; Genomic_DNA.
DR EMBL; M17929; AAA40760.1; JOINED; Genomic_DNA.
DR EMBL; M17930; AAA40760.1; JOINED; Genomic_DNA.
DR EMBL; BC091158; AAH91158.1; -; mRNA.
DR PIR; A26702; A26702.
DR RefSeq; NP_058830.2; NM_017134.3.
DR PDB; 1D3V; X-ray; 1.70 A; A/B=1-323.
DR PDB; 1HQ5; X-ray; 2.30 A; A/B=1-323.
DR PDB; 1HQF; X-ray; 2.90 A; A/B/C=1-323.
DR PDB; 1HQG; X-ray; 2.00 A; A/B/C=1-323.
DR PDB; 1HQH; X-ray; 2.80 A; A/B/C=1-323.
DR PDB; 1HQX; X-ray; 3.00 A; A/B/C=1-323.
DR PDB; 1P8M; X-ray; 2.84 A; A/B/C=6-319.
DR PDB; 1P8N; X-ray; 2.90 A; A/B/C=6-319.
DR PDB; 1P8O; X-ray; 2.96 A; A/B/C=6-319.
DR PDB; 1P8P; X-ray; 2.50 A; A/B/C=6-319.
DR PDB; 1P8Q; X-ray; 2.95 A; A/B/C=6-319.
DR PDB; 1P8R; X-ray; 2.50 A; A/B=6-313.
DR PDB; 1P8S; X-ray; 3.20 A; A/B/C=6-319.
DR PDB; 1R1O; X-ray; 2.80 A; A/B/C=1-323.
DR PDB; 1RLA; X-ray; 2.10 A; A/B/C=1-323.
DR PDB; 1T4P; X-ray; 2.60 A; A/B/C=6-319.
DR PDB; 1T4R; X-ray; 2.60 A; A/B/C=6-319.
DR PDB; 1T4S; X-ray; 2.80 A; A/B/C=6-319.
DR PDB; 1T4T; X-ray; 2.20 A; A/B/C=6-319.
DR PDB; 1T5F; X-ray; 2.20 A; A/B/C=6-319.
DR PDB; 1T5G; X-ray; 2.40 A; A/B/C=6-319.
DR PDB; 1TA1; X-ray; 2.50 A; A/B/C=6-319.
DR PDB; 1TBH; X-ray; 2.70 A; A/B/C=6-319.
DR PDB; 1TBJ; X-ray; 2.80 A; A/B/C=6-319.
DR PDB; 1TBL; X-ray; 3.10 A; A/B/C=6-319.
DR PDB; 1ZPE; X-ray; 1.70 A; A/B/C=6-319.
DR PDB; 1ZPG; X-ray; 1.90 A; A/B/C=6-319.
DR PDB; 2RLA; X-ray; 3.00 A; A/B/C=1-323.
DR PDB; 3E8Q; X-ray; 2.90 A; A/B/C=1-323.
DR PDB; 3E8Z; X-ray; 2.00 A; A/B/C=1-323.
DR PDB; 3E9B; X-ray; 2.15 A; A/B/C=1-323.
DR PDB; 3RLA; X-ray; 2.54 A; A/B/C=1-323.
DR PDB; 4RLA; X-ray; 2.94 A; A/B/C=1-323.
DR PDB; 5RLA; X-ray; 2.74 A; A/B/C=1-323.
DR PDBsum; 1D3V; -.
DR PDBsum; 1HQ5; -.
DR PDBsum; 1HQF; -.
DR PDBsum; 1HQG; -.
DR PDBsum; 1HQH; -.
DR PDBsum; 1HQX; -.
DR PDBsum; 1P8M; -.
DR PDBsum; 1P8N; -.
DR PDBsum; 1P8O; -.
DR PDBsum; 1P8P; -.
DR PDBsum; 1P8Q; -.
DR PDBsum; 1P8R; -.
DR PDBsum; 1P8S; -.
DR PDBsum; 1R1O; -.
DR PDBsum; 1RLA; -.
DR PDBsum; 1T4P; -.
DR PDBsum; 1T4R; -.
DR PDBsum; 1T4S; -.
DR PDBsum; 1T4T; -.
DR PDBsum; 1T5F; -.
DR PDBsum; 1T5G; -.
DR PDBsum; 1TA1; -.
DR PDBsum; 1TBH; -.
DR PDBsum; 1TBJ; -.
DR PDBsum; 1TBL; -.
DR PDBsum; 1ZPE; -.
DR PDBsum; 1ZPG; -.
DR PDBsum; 2RLA; -.
DR PDBsum; 3E8Q; -.
DR PDBsum; 3E8Z; -.
DR PDBsum; 3E9B; -.
DR PDBsum; 3RLA; -.
DR PDBsum; 4RLA; -.
DR PDBsum; 5RLA; -.
DR AlphaFoldDB; P07824; -.
DR SMR; P07824; -.
DR BioGRID; 247899; 3.
DR IntAct; P07824; 1.
DR STRING; 10116.ENSRNOP00000017911; -.
DR BindingDB; P07824; -.
DR ChEMBL; CHEMBL3232699; -.
DR CarbonylDB; P07824; -.
DR iPTMnet; P07824; -.
DR PhosphoSitePlus; P07824; -.
DR PaxDb; P07824; -.
DR PRIDE; P07824; -.
DR GeneID; 29221; -.
DR KEGG; rno:29221; -.
DR CTD; 383; -.
DR RGD; 2150; Arg1.
DR VEuPathDB; HostDB:ENSRNOG00000013304; -.
DR eggNOG; KOG2965; Eukaryota.
DR HOGENOM; CLU_039478_6_1_1; -.
DR InParanoid; P07824; -.
DR OMA; DTPFQIV; -.
DR OrthoDB; 1179130at2759; -.
DR PhylomeDB; P07824; -.
DR TreeFam; TF300034; -.
DR BRENDA; 3.5.3.1; 5301.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-70635; Urea cycle.
DR SABIO-RK; P07824; -.
DR UniPathway; UPA00158; UER00270.
DR EvolutionaryTrace; P07824; -.
DR PRO; PR:P07824; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000013304; Expressed in liver and 19 other tissues.
DR Genevisible; P07824; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0004053; F:arginase activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0030145; F:manganese ion binding; IDA:RGD.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0019547; P:arginine catabolic process to ornithine; IDA:RGD.
DR GO; GO:0006525; P:arginine metabolic process; IDA:RGD.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0071377; P:cellular response to glucagon stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; 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:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0032964; P:collagen biosynthetic process; IMP:RGD.
DR GO; GO:0042832; P:defense response to protozoan; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0060056; P:mammary gland involution; IEP:RGD.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEP:RGD.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:RGD.
DR GO; GO:0060336; P:negative regulation of interferon-gamma-mediated signaling pathway; ISO:RGD.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; ISO:RGD.
DR GO; GO:2000552; P:negative regulation of T-helper 2 cell cytokine production; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:RGD.
DR GO; GO:0070965; P:positive regulation of neutrophil mediated killing of fungus; ISO:RGD.
DR GO; GO:1905541; P:regulation of L-arginine import across plasma membrane; IDA: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:0009635; P:response to herbicide; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0010042; P:response to manganese ion; IEP:RGD.
DR GO; GO:0051597; P:response to methylmercury; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0010269; P:response to selenium ion; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0033189; P:response to vitamin A; IEP:RGD.
DR GO; GO:0033197; P:response to vitamin E; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IEP:RGD.
DR GO; GO:0000050; P:urea cycle; IDA:RGD.
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 3D-structure; Adaptive immunity; Arginine metabolism; Cytoplasm; Hydrolase;
KW Immunity; Innate immunity; Manganese; Metal-binding; Phosphoprotein;
KW Reference proteome; Urea cycle.
FT CHAIN 1..323
FT /note="Arginase-1"
FT /id="PRO_0000173697"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 101
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0007744|PDB:1D3V, ECO:0007744|PDB:1HQ5,
FT ECO:0007744|PDB:1HQF, ECO:0007744|PDB:1HQG,
FT ECO:0007744|PDB:1HQH, ECO:0007744|PDB:1HQX,
FT ECO:0007744|PDB:1P8M, ECO:0007744|PDB:1P8N,
FT ECO:0007744|PDB:1P8O, ECO:0007744|PDB:1P8Q,
FT ECO:0007744|PDB:1P8S, ECO:0007744|PDB:1R1O,
FT ECO:0007744|PDB:1RLA, ECO:0007744|PDB:1T4P,
FT ECO:0007744|PDB:1T4R, ECO:0007744|PDB:1T4S,
FT ECO:0007744|PDB:1T4T, ECO:0007744|PDB:1T5F,
FT ECO:0007744|PDB:1T5G, ECO:0007744|PDB:1TA1,
FT ECO:0007744|PDB:1TBH, ECO:0007744|PDB:1TBJ,
FT ECO:0007744|PDB:1TBL, ECO:0007744|PDB:1ZPE,
FT ECO:0007744|PDB:1ZPG, ECO:0007744|PDB:3E8Q,
FT ECO:0007744|PDB:3E8Z, ECO:0007744|PDB:3E9B"
FT BINDING 124
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0000269|PubMed:9265637, ECO:0007744|PDB:1D3V,
FT ECO:0007744|PDB:1HQ5, ECO:0007744|PDB:1HQF,
FT ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1HQX, ECO:0007744|PDB:1P8M,
FT ECO:0007744|PDB:1P8N, ECO:0007744|PDB:1P8O,
FT ECO:0007744|PDB:1P8P, ECO:0007744|PDB:1P8Q,
FT ECO:0007744|PDB:1P8R, ECO:0007744|PDB:1P8S,
FT ECO:0007744|PDB:1R1O, ECO:0007744|PDB:1RLA,
FT ECO:0007744|PDB:1T4P, ECO:0007744|PDB:1T4R,
FT ECO:0007744|PDB:1T4S, ECO:0007744|PDB:1T4T,
FT ECO:0007744|PDB:1T5F, ECO:0007744|PDB:1T5G,
FT ECO:0007744|PDB:1TA1, ECO:0007744|PDB:1TBH,
FT ECO:0007744|PDB:1TBJ, ECO:0007744|PDB:1TBL,
FT ECO:0007744|PDB:1ZPE, ECO:0007744|PDB:1ZPG,
FT ECO:0007744|PDB:3E8Q, ECO:0007744|PDB:3E8Z,
FT ECO:0007744|PDB:3E9B, ECO:0007744|PDB:3RLA"
FT BINDING 124
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0000269|PubMed:9265637, ECO:0007744|PDB:1D3V,
FT ECO:0007744|PDB:1HQ5, ECO:0007744|PDB:1HQF,
FT ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1HQX, ECO:0007744|PDB:1P8M,
FT ECO:0007744|PDB:1P8O, ECO:0007744|PDB:1P8P,
FT ECO:0007744|PDB:1P8Q, ECO:0007744|PDB:1P8R,
FT ECO:0007744|PDB:1P8S, ECO:0007744|PDB:1R1O,
FT ECO:0007744|PDB:1RLA, ECO:0007744|PDB:1T4P,
FT ECO:0007744|PDB:1T4R, ECO:0007744|PDB:1T4S,
FT ECO:0007744|PDB:1T4T, ECO:0007744|PDB:1T5F,
FT ECO:0007744|PDB:1T5G, ECO:0007744|PDB:1TA1,
FT ECO:0007744|PDB:1TBH, ECO:0007744|PDB:1TBJ,
FT ECO:0007744|PDB:1TBL, ECO:0007744|PDB:1ZPE,
FT ECO:0007744|PDB:1ZPG, ECO:0007744|PDB:2RLA,
FT ECO:0007744|PDB:3E8Q, ECO:0007744|PDB:3E8Z,
FT ECO:0007744|PDB:3E9B, ECO:0007744|PDB:3RLA,
FT ECO:0007744|PDB:4RLA, ECO:0007744|PDB:5RLA"
FT BINDING 126..130
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1T5G"
FT BINDING 126
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0000269|PubMed:9265637, ECO:0007744|PDB:1D3V,
FT ECO:0007744|PDB:1HQ5, ECO:0007744|PDB:1HQF,
FT ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1HQX, ECO:0007744|PDB:1P8M,
FT ECO:0007744|PDB:1P8O, ECO:0007744|PDB:1P8P,
FT ECO:0007744|PDB:1P8Q, ECO:0007744|PDB:1P8R,
FT ECO:0007744|PDB:1P8S, ECO:0007744|PDB:1R1O,
FT ECO:0007744|PDB:1RLA, ECO:0007744|PDB:1T4P,
FT ECO:0007744|PDB:1T4R, ECO:0007744|PDB:1T4S,
FT ECO:0007744|PDB:1T4T, ECO:0007744|PDB:1T5F,
FT ECO:0007744|PDB:1T5G, ECO:0007744|PDB:1TA1,
FT ECO:0007744|PDB:1TBH, ECO:0007744|PDB:1TBJ,
FT ECO:0007744|PDB:1TBL, ECO:0007744|PDB:1ZPE,
FT ECO:0007744|PDB:1ZPG, ECO:0007744|PDB:2RLA,
FT ECO:0007744|PDB:3E8Q, ECO:0007744|PDB:3E8Z,
FT ECO:0007744|PDB:3E9B, ECO:0007744|PDB:3RLA,
FT ECO:0007744|PDB:4RLA, ECO:0007744|PDB:5RLA"
FT BINDING 128
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0000269|PubMed:9265637, ECO:0007744|PDB:1D3V,
FT ECO:0007744|PDB:1HQ5, ECO:0007744|PDB:1HQF,
FT ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1HQX, ECO:0007744|PDB:1P8N,
FT ECO:0007744|PDB:1P8P, ECO:0007744|PDB:1P8Q,
FT ECO:0007744|PDB:1P8R, ECO:0007744|PDB:1P8S,
FT ECO:0007744|PDB:1R1O, ECO:0007744|PDB:1RLA,
FT ECO:0007744|PDB:1T4P, ECO:0007744|PDB:1T4R,
FT ECO:0007744|PDB:1T4S, ECO:0007744|PDB:1T4T,
FT ECO:0007744|PDB:1T5F, ECO:0007744|PDB:1T5G,
FT ECO:0007744|PDB:1TA1, ECO:0007744|PDB:1TBH,
FT ECO:0007744|PDB:1TBJ, ECO:0007744|PDB:1TBL,
FT ECO:0007744|PDB:1ZPE, ECO:0007744|PDB:1ZPG,
FT ECO:0007744|PDB:3E8Q, ECO:0007744|PDB:3E8Z,
FT ECO:0007744|PDB:3E9B, ECO:0007744|PDB:3RLA"
FT BINDING 137..139
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH"
FT BINDING 183
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:1T5G"
FT BINDING 232
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0000269|PubMed:9265637, ECO:0007744|PDB:1D3V,
FT ECO:0007744|PDB:1HQ5, ECO:0007744|PDB:1HQF,
FT ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1HQX, ECO:0007744|PDB:1P8M,
FT ECO:0007744|PDB:1P8O, ECO:0007744|PDB:1P8P,
FT ECO:0007744|PDB:1P8Q, ECO:0007744|PDB:1P8R,
FT ECO:0007744|PDB:1R1O, ECO:0007744|PDB:1RLA,
FT ECO:0007744|PDB:1T4P, ECO:0007744|PDB:1T4R,
FT ECO:0007744|PDB:1T4S, ECO:0007744|PDB:1T4T,
FT ECO:0007744|PDB:1T5F, ECO:0007744|PDB:1T5G,
FT ECO:0007744|PDB:1TA1, ECO:0007744|PDB:1TBH,
FT ECO:0007744|PDB:1TBJ, ECO:0007744|PDB:1TBL,
FT ECO:0007744|PDB:1ZPE, ECO:0007744|PDB:1ZPG,
FT ECO:0007744|PDB:3E8Q, ECO:0007744|PDB:3E8Z,
FT ECO:0007744|PDB:3E9B, ECO:0007744|PDB:3RLA"
FT BINDING 232
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0000269|PubMed:9265637, ECO:0007744|PDB:1D3V,
FT ECO:0007744|PDB:1HQ5, ECO:0007744|PDB:1HQF,
FT ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1HQX, ECO:0007744|PDB:1P8M,
FT ECO:0007744|PDB:1P8O, ECO:0007744|PDB:1P8P,
FT ECO:0007744|PDB:1P8Q, ECO:0007744|PDB:1P8R,
FT ECO:0007744|PDB:1R1O, ECO:0007744|PDB:1RLA,
FT ECO:0007744|PDB:1T4P, ECO:0007744|PDB:1T4R,
FT ECO:0007744|PDB:1T4S, ECO:0007744|PDB:1T4T,
FT ECO:0007744|PDB:1T5F, ECO:0007744|PDB:1T5G,
FT ECO:0007744|PDB:1TA1, ECO:0007744|PDB:1TBH,
FT ECO:0007744|PDB:1TBJ, ECO:0007744|PDB:1TBL,
FT ECO:0007744|PDB:1ZPE, ECO:0007744|PDB:1ZPG,
FT ECO:0007744|PDB:2RLA, ECO:0007744|PDB:3E8Q,
FT ECO:0007744|PDB:3E8Z, ECO:0007744|PDB:3E9B,
FT ECO:0007744|PDB:3RLA, ECO:0007744|PDB:4RLA,
FT ECO:0007744|PDB:5RLA"
FT BINDING 234
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10542097,
FT ECO:0000269|PubMed:12820884, ECO:0000269|PubMed:15315440,
FT ECO:0000269|PubMed:16266687, ECO:0000269|PubMed:8849731,
FT ECO:0000269|PubMed:9265637, ECO:0007744|PDB:1D3V,
FT ECO:0007744|PDB:1HQ5, ECO:0007744|PDB:1HQF,
FT ECO:0007744|PDB:1HQG, ECO:0007744|PDB:1HQH,
FT ECO:0007744|PDB:1HQX, ECO:0007744|PDB:1P8M,
FT ECO:0007744|PDB:1P8O, ECO:0007744|PDB:1P8P,
FT ECO:0007744|PDB:1P8R, ECO:0007744|PDB:1P8S,
FT ECO:0007744|PDB:1R1O, ECO:0007744|PDB:1RLA,
FT ECO:0007744|PDB:1T4P, ECO:0007744|PDB:1T4R,
FT ECO:0007744|PDB:1T4S, ECO:0007744|PDB:1T4T,
FT ECO:0007744|PDB:1T5F, ECO:0007744|PDB:1T5G,
FT ECO:0007744|PDB:1TA1, ECO:0007744|PDB:1TBH,
FT ECO:0007744|PDB:1TBJ, ECO:0007744|PDB:1TBL,
FT ECO:0007744|PDB:1ZPE, ECO:0007744|PDB:1ZPG,
FT ECO:0007744|PDB:2RLA, ECO:0007744|PDB:3E8Q,
FT ECO:0007744|PDB:3E8Z, ECO:0007744|PDB:3E9B,
FT ECO:0007744|PDB:3RLA, ECO:0007744|PDB:4RLA,
FT ECO:0007744|PDB:5RLA"
FT BINDING 246
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P53608"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P78540"
FT MOD_RES 17
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61176"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61176"
FT MOD_RES 75
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61176"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05089"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05089"
FT MOD_RES 281
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 101
FT /note="H->E: Reduced catalytic activity. No effect on
FT manganese binding."
FT /evidence="ECO:0000269|PubMed:12820884"
FT MUTAGEN 128
FT /note="D->E,N: Reduced manganese binding and strongly
FT reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:12820884"
FT MUTAGEN 141
FT /note="H->A,C,D: Strongly reduced catalytic activity. Minor
FT effect on affinity for arginine."
FT /evidence="ECO:0000269|PubMed:16266687"
FT MUTAGEN 141
FT /note="H->N: Reduced affinity for arginine and reduced
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:16266687"
FT MUTAGEN 232
FT /note="D->A: Loss of one manganese ion and strongly reduced
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12820884"
FT MUTAGEN 232
FT /note="D->C: Reduced manganese binding and strongly reduced
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12820884"
FT MUTAGEN 234
FT /note="D->A,E,H: Reduced manganese binding and strongly
FT reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:12820884"
FT MUTAGEN 235
FT /note="G->A: 56% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:11883902"
FT MUTAGEN 235
FT /note="G->R: Loss of manganese-binding and activity."
FT /evidence="ECO:0000269|PubMed:11883902"
FT CONFLICT 298
FT /note="A -> P (in Ref. 1; AAA40761/AAA40760)"
FT /evidence="ECO:0000305"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:1ZPE"
FT HELIX 22..26
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 36..40
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:5RLA"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1ZPE"
FT HELIX 70..89
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:1D3V"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:1TBH"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 144..148
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:1P8O"
FT TURN 160..164
FT /evidence="ECO:0007829|PDB:1HQH"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 174..179
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 184..193
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 208..220
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:3E9B"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:1D3V"
FT TURN 238..240
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 254..267
FT /evidence="ECO:0007829|PDB:1D3V"
FT STRAND 270..276
FT /evidence="ECO:0007829|PDB:1D3V"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:1ZPE"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:1P8R"
FT HELIX 286..303
FT /evidence="ECO:0007829|PDB:1D3V"
SQ SEQUENCE 323 AA; 34973 MW; 5A92CB0931F9A053 CRC64;
MSSKPKPIEI IGAPFSKGQP RGGVEKGPAA LRKAGLVEKL KETEYNVRDH GDLAFVDVPN
DSPFQIVKNP RSVGKANEQL AAVVAETQKN GTISVVLGGD HSMAIGSISG HARVHPDLCV
IWVDAHTDIN TPLTTSSGNL HGQPVAFLLK ELKGKFPDVP GFSWVTPCIS AKDIVYIGLR
DVDPGEHYII KTLGIKYFSM TEVDKLGIGK VMEETFSYLL GRKKRPIHLS FDVDGLDPVF
TPATGTPVVG GLSYREGLYI TEEIYKTGLL SGLDIMEVNP TLGKTPEEVT RTVNTAVALT
LSCFGTKREG NHKPETDYLK PPK
