ID KYNU_RAT Reviewed; 464 AA. AC P70712; Q68G25; Q7M0D0; Q9QW90; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 09-NOV-2004, sequence version 2. DT 12-AUG-2020, entry version 152. DE RecName: Full=Kynureninase {ECO:0000255|HAMAP-Rule:MF_03017}; DE EC=3.7.1.3 {ECO:0000255|HAMAP-Rule:MF_03017}; DE AltName: Full=L-kynurenine hydrolase {ECO:0000255|HAMAP-Rule:MF_03017}; GN Name=Kynu; 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 PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, AND ACETYLATION AT RP MET-1. RC STRAIN=Wistar; TISSUE=Liver; RX PubMed=7578221; DOI=10.1016/0167-4838(95)00166-r; RA Takeuchi F., Tsubouchi R., Yoshino M., Shibata Y.; RT "Amino-acid sequence of rat liver kynureninase."; RL Biochim. Biophys. Acta 1252:185-188(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC RP ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE RP SPECIFICITY. RC TISSUE=Liver; RX PubMed=9180257; DOI=10.1016/s0014-5793(97)00374-8; RA Toma S., Nakamura M., Tone S., Okuno E., Kido R., Breton J., Avanzi N., RA Cozzi L., Speciale C., Mostardini M., Gatti S., Benatti L.; RT "Cloning and recombinant expression of rat and human kynureninase."; RL FEBS Lett. 408:5-10(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 19-117, AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Kidney, and Liver; RX PubMed=8706755; DOI=10.1111/j.1432-1033.1996.0460u.x; RA Alberati-Giani D., Buchli R., Malherbe P., Broger C., Lang G., Koehler C., RA Lahm H.-W., Cesura A.M.; RT "Isolation and expression of a cDNA clone encoding human kynureninase."; RL Eur. J. Biochem. 239:460-468(1996). RN [5] RP PROTEIN SEQUENCE OF 83-116 AND 273-319. RC TISSUE=Liver; RA Matsui Lee I.S., Okuno E., Kido R.; RL Submitted (JUN-1992) to the PIR data bank. RN [6] 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). CC -!- FUNCTION: Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3- CC hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3- CC hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for CC the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity. CC {ECO:0000255|HAMAP-Rule:MF_03017, ECO:0000269|PubMed:9180257}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-kynurenine = anthranilate + H(+) + L-alanine; CC Xref=Rhea:RHEA:16813, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16567, ChEBI:CHEBI:57959, ChEBI:CHEBI:57972; EC=3.7.1.3; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03017, CC ECO:0000269|PubMed:9180257}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3-hydroxy-L-kynurenine + H2O = 3-hydroxyanthranilate + H(+) + CC L-alanine; Xref=Rhea:RHEA:25143, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36559, ChEBI:CHEBI:57972, CC ChEBI:CHEBI:58125; EC=3.7.1.3; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03017, ECO:0000269|PubMed:9180257}; CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC -!- ACTIVITY REGULATION: Inhibited by o-methylbenzoylalanine (OMBA). CC {ECO:0000269|PubMed:9180257}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=440 uM for L-kynurenine {ECO:0000269|PubMed:9180257}; CC KM=32 uM for DL-3-hydroxykynurenine {ECO:0000269|PubMed:9180257}; CC pH dependence: CC Optimum pH is about 9.0 with L-kynurenine as substrate, and about 8.5 CC with DL-3-hydroxykynurenine as substrate. CC {ECO:0000269|PubMed:9180257}; CC -!- PATHWAY: Amino-acid degradation; L-kynurenine degradation; L-alanine CC and anthranilate from L-kynurenine: step 1/1. {ECO:0000255|HAMAP- CC Rule:MF_03017}. CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from CC L-kynurenine: step 2/3. {ECO:0000255|HAMAP-Rule:MF_03017}. CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03017}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000255|HAMAP- CC Rule:MF_03017}. CC -!- TISSUE SPECIFICITY: High levels in liver and kidney. Also detected in CC heart, retina, ovary. Lung, testis and brain. CC {ECO:0000269|PubMed:9180257}. CC -!- INDUCTION: Inhibited by thiol reagents and heavy metal ions. CC -!- SIMILARITY: Belongs to the kynureninase family. {ECO:0000255|HAMAP- CC Rule:MF_03017}. 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; U68168; AAC53206.1; -; mRNA. DR EMBL; BC078762; AAH78762.1; -; mRNA. DR PIR; PS0370; PS0370. DR PIR; S59898; S59898. DR PIR; T48675; T48675. DR RefSeq; NP_446354.1; NM_053902.2. DR SMR; P70712; -. DR STRING; 10116.ENSRNOP00000050947; -. DR BindingDB; P70712; -. DR ChEMBL; CHEMBL2969; -. DR iPTMnet; P70712; -. DR PhosphoSitePlus; P70712; -. DR PaxDb; P70712; -. DR PRIDE; P70712; -. DR Ensembl; ENSRNOT00000043533; ENSRNOP00000050947; ENSRNOG00000029993. DR GeneID; 116682; -. DR KEGG; rno:116682; -. DR UCSC; RGD:71061; rat. DR CTD; 8942; -. DR RGD; 71061; Kynu. DR eggNOG; KOG3846; Eukaryota. DR GeneTree; ENSGT00390000008033; -. DR HOGENOM; CLU_003433_4_0_1; -. DR InParanoid; P70712; -. DR KO; K01556; -. DR OMA; AGWWGHD; -. DR OrthoDB; 916879at2759; -. DR PhylomeDB; P70712; -. DR BioCyc; MetaCyc:MONOMER-15007; -. DR Reactome; R-RNO-71240; Tryptophan catabolism. DR SABIO-RK; P70712; -. DR UniPathway; UPA00253; UER00329. DR UniPathway; UPA00334; UER00455. DR PRO; PR:P70712; -. DR Proteomes; UP000002494; Chromosome 3. DR Bgee; ENSRNOG00000029993; Expressed in liver and 19 other tissues. DR Genevisible; P70712; RN. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:RGD. DR GO; GO:0005739; C:mitochondrion; ISO:RGD. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0061981; F:3-hydroxykynureninase activity; ISS:UniProtKB. DR GO; GO:0030429; F:kynureninase activity; IDA:RGD. DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD. DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:RGD. DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IEA:UniProtKB-UniRule. DR GO; GO:0007568; P:aging; IEP:RGD. DR GO; GO:0043420; P:anthranilate metabolic process; ISO:RGD. DR GO; GO:0097053; P:L-kynurenine catabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0009435; P:NAD biosynthetic process; ISS:UniProtKB. DR GO; GO:0019805; P:quinolinate biosynthetic process; ISO:RGD. DR GO; GO:0034341; P:response to interferon-gamma; ISO:RGD. DR GO; GO:0034516; P:response to vitamin B6; ISO:RGD. DR GO; GO:0006569; P:tryptophan catabolic process; ISO:RGD. DR GO; GO:0019442; P:tryptophan catabolic process to acetyl-CoA; IDA:RGD. DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IBA:GO_Central. DR Gene3D; 3.40.640.10; -; 1. DR Gene3D; 3.90.1150.10; -; 1. DR HAMAP; MF_01970; Kynureninase; 1. DR InterPro; IPR000192; Aminotrans_V_dom. DR InterPro; IPR010111; Kynureninase. DR InterPro; IPR015424; PyrdxlP-dep_Trfase. DR InterPro; IPR015422; PyrdxlP-dep_Trfase_dom1. DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major. DR PANTHER; PTHR14084; PTHR14084; 1. DR Pfam; PF00266; Aminotran_5; 1. DR PIRSF; PIRSF038800; KYNU; 1. DR SUPFAM; SSF53383; SSF53383; 1. DR TIGRFAMs; TIGR01814; kynureninase; 1. PE 1: Evidence at protein level; KW Acetylation; Cytoplasm; Direct protein sequencing; Hydrolase; KW Pyridine nucleotide biosynthesis; Pyridoxal phosphate; Reference proteome. FT CHAIN 1..464 FT /note="Kynureninase" FT /id="PRO_0000218659" FT REGION 165..168 FT /note="Pyridoxal phosphate binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 137 FT /note="Pyridoxal phosphate; via amide nitrogen" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 138 FT /note="Pyridoxal phosphate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 221 FT /note="Pyridoxal phosphate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 250 FT /note="Pyridoxal phosphate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 253 FT /note="Pyridoxal phosphate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 275 FT /note="Pyridoxal phosphate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 305 FT /note="Pyridoxal phosphate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT BINDING 333 FT /note="Pyridoxal phosphate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017, FT ECO:0000269|PubMed:7578221" FT MOD_RES 276 FT /note="N6-(pyridoxal phosphate)lysine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017" FT CONFLICT 18 FT /note="T -> A (in Ref. 2; AAC53206)" FT /evidence="ECO:0000305" FT CONFLICT 26 FT /note="D -> N (in Ref. 1; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 118 FT /note="S -> T (in Ref. 2; AAC53206)" FT /evidence="ECO:0000305" SQ SEQUENCE 464 AA; 52470 MW; 1490A74EFF7287AC CRC64; MEPSPLELPV DAVRRIATEL NCDPTDERVA LRLDEEDKLK RFKDCFYIPK MRDLPSIDLS LVNEDDNAIY FLGNSLGLQP KMVKTYLEEE LDKWAKIGAY GHEVGKRPWI IGDESIVSLM KDIVGAHEKE IALMNALTVN LHLLLLSFFK PTPKRHKILL EAKAFPSDHY AIESQIQLHG LDVEKSMRMI KPREGEETLR MEDILEVIEK EGDSIAVVLF SGLHFYTGQL FNIPAITQAG HAKGCFVGFD LAHAVGNVEL HLHDWDVDFA CWCSYKYLNS GAGGLAGAFI HEKHAHTIKP ALVGWFGHEL STRFNMDNKL QLIPGVNGFR ISNPPILLVC SLHASLEIFQ QATMTALRRK SILLTGYLEY LLKHYHGGND TENKRPVVNI ITPSRAEERG CQLTLTFSIS KKGVFKELEK RGVVCDKREP EGIRVAPVPL YNSFHDVYKF IRLLTAILDS TERN //