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   24-JAN-2024, entry version 163.
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}.
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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   AlphaFoldDB; P70712; -.
DR   SMR; P70712; -.
DR   STRING; 10116.ENSRNOP00000050947; -.
DR   BindingDB; P70712; -.
DR   ChEMBL; CHEMBL2969; -.
DR   iPTMnet; P70712; -.
DR   PhosphoSitePlus; P70712; -.
DR   PaxDb; 10116-ENSRNOP00000050947; -.
DR   GeneID; 116682; -.
DR   KEGG; rno:116682; -.
DR   UCSC; RGD:71061; rat.
DR   AGR; RGD:71061; -.
DR   CTD; 8942; -.
DR   RGD; 71061; Kynu.
DR   VEuPathDB; HostDB:ENSRNOG00000029993; -.
DR   eggNOG; KOG3846; Eukaryota.
DR   HOGENOM; CLU_003433_4_0_1; -.
DR   InParanoid; P70712; -.
DR   OrthoDB; 5471916at2759; -.
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 12 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0005739; C:mitochondrion; ISO:RGD.
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: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 type II interferon; 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; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR   Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 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.
DR   InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR   NCBIfam; TIGR01814; kynureninase; 1.
DR   PANTHER; PTHR14084; KYNURENINASE; 1.
DR   PANTHER; PTHR14084:SF0; KYNURENINASE; 1.
DR   Pfam; PF00266; Aminotran_5; 1.
DR   PIRSF; PIRSF038800; KYNU; 1.
DR   SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR   Genevisible; P70712; RN.
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   BINDING         137
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         138
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         165..168
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         221
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         250
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         253
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         275
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         305
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
FT   BINDING         333
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
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
//