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 27-MAY-2015, entry version 122. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, AND ACETYLATION RP AT 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, RP CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, RP AND TISSUE 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., RA Avanzi N., 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 RT project: 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., RA Koehler C., Lahm H.-W., Cesura A.M.; RT "Isolation and expression of a cDNA clone encoding human RT 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. 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 CC for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase CC activity. {ECO:0000255|HAMAP-Rule:MF_03017, CC ECO:0000269|PubMed:9180257}. CC -!- CATALYTIC ACTIVITY: L-kynurenine + H(2)O = anthranilate + L- CC alanine. {ECO:0000255|HAMAP-Rule:MF_03017, CC ECO:0000269|PubMed:9180257}. CC -!- CATALYTIC ACTIVITY: L-3-hydroxykynurenine + H(2)O = 3- CC hydroxyanthranilate + L-alanine. {ECO:0000255|HAMAP-Rule:MF_03017, CC ECO:0000269|PubMed:9180257}. CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC -!- ENZYME 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 CC {ECO:0000269|PubMed:9180257}; CC pH dependence: CC Optimum pH is about 9.0 with L-kynurenine as substrate, and CC about 8.5 with DL-3-hydroxykynurenine as substrate. CC {ECO:0000269|PubMed:9180257}; CC -!- PATHWAY: Amino-acid degradation; L-kynurenine degradation; L- CC alanine and anthranilate from L-kynurenine: step 1/1. CC {ECO:0000255|HAMAP-Rule:MF_03017}. CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate CC from L-kynurenine: step 2/3. {ECO:0000255|HAMAP-Rule:MF_03017}. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: High levels in liver and kidney. Also detected CC in 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. CC {ECO:0000255|HAMAP-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 UniGene; Rn.10575; -. DR ProteinModelPortal; P70712; -. DR SMR; P70712; 6-460. DR BindingDB; P70712; -. DR ChEMBL; CHEMBL2969; -. 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; COG3844; -. DR GeneTree; ENSGT00390000008033; -. DR HOGENOM; HOG000242438; -. DR HOVERGEN; HBG001170; -. DR InParanoid; P70712; -. DR KO; K01556; -. DR OMA; GWYGGDK; -. DR OrthoDB; EOG7D2FDV; -. DR PhylomeDB; P70712; -. DR BioCyc; MetaCyc:MONOMER-15007; -. DR Reactome; REACT_350374; Tryptophan catabolism. DR SABIO-RK; P70712; -. DR UniPathway; UPA00253; UER00329. DR UniPathway; UPA00334; UER00455. DR NextBio; 619528; -. DR PRO; PR:P70712; -. DR Proteomes; UP000002494; Chromosome 3. DR Genevestigator; P70712; -. DR GO; GO:0005829; C:cytosol; IDA:RGD. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0030429; F:kynureninase activity; IDA: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-HAMAP. DR GO; GO:0043420; P:anthranilate metabolic process; IEA:UniProtKB-HAMAP. DR GO; GO:0097053; P:L-kynurenine catabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0019805; P:quinolinate biosynthetic process; IEA:UniProtKB-HAMAP. DR GO; GO:0034341; P:response to interferon-gamma; IEA:Ensembl. DR GO; GO:0034516; P:response to vitamin B6; IEA:Ensembl. DR GO; GO:0019442; P:tryptophan catabolic process to acetyl-CoA; IDA:RGD. DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IDA:RGD. 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; IPR015421; PyrdxlP-dep_Trfase_major_sub1. DR InterPro; IPR015422; PyrdxlP-dep_Trfase_major_sub2. 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; Complete proteome; Cytoplasm; Direct protein sequencing; KW Hydrolase; Pyridine nucleotide biosynthesis; Pyridoxal phosphate; KW Reference proteome. FT CHAIN 1 464 Kynureninase. FT /FTId=PRO_0000218659. FT REGION 165 168 Pyridoxal phosphate binding. FT {ECO:0000255|HAMAP-Rule:MF_03017}. FT BINDING 137 137 Pyridoxal phosphate; via amide nitrogen. FT {ECO:0000255|HAMAP-Rule:MF_03017}. FT BINDING 138 138 Pyridoxal phosphate. {ECO:0000255|HAMAP- FT Rule:MF_03017}. FT BINDING 221 221 Pyridoxal phosphate. {ECO:0000255|HAMAP- FT Rule:MF_03017}. FT BINDING 250 250 Pyridoxal phosphate. {ECO:0000255|HAMAP- FT Rule:MF_03017}. FT BINDING 253 253 Pyridoxal phosphate. {ECO:0000255|HAMAP- FT Rule:MF_03017}. FT BINDING 275 275 Pyridoxal phosphate. {ECO:0000255|HAMAP- FT Rule:MF_03017}. FT BINDING 305 305 Pyridoxal phosphate. {ECO:0000255|HAMAP- FT Rule:MF_03017}. FT BINDING 333 333 Pyridoxal phosphate. {ECO:0000255|HAMAP- FT Rule:MF_03017}. FT MOD_RES 1 1 N-acetylmethionine. {ECO:0000255|HAMAP- FT Rule:MF_03017, FT ECO:0000269|PubMed:7578221}. FT MOD_RES 276 276 N6-(pyridoxal phosphate)lysine. FT {ECO:0000255|HAMAP-Rule:MF_03017}. FT CONFLICT 18 18 T -> A (in Ref. 2; AAC53206). FT {ECO:0000305}. FT CONFLICT 26 26 D -> N (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 118 118 S -> T (in Ref. 2; AAC53206). FT {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 //