KYNU_MOUSE
ID KYNU_MOUSE Reviewed; 464 AA.
AC Q9CXF0;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 3.
DT 03-AUG-2022, entry version 149.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3]
RP PATHWAY, AND DISRUPTION PHENOTYPE.
RX PubMed=28792876; DOI=10.1056/nejmoa1616361;
RA Shi H., Enriquez A., Rapadas M., Martin E.M.M.A., Wang R., Moreau J.,
RA Lim C.K., Szot J.O., Ip E., Hughes J.N., Sugimoto K., Humphreys D.T.,
RA McInerney-Leo A.M., Leo P.J., Maghzal G.J., Halliday J., Smith J.,
RA Colley A., Mark P.R., Collins F., Sillence D.O., Winlaw D.S., Ho J.W.K.,
RA Guillemin G.J., Brown M.A., Kikuchi K., Thomas P.Q., Stocker R.,
RA Giannoulatou E., Chapman G., Duncan E.L., Sparrow D.B., Dunwoodie S.L.;
RT "NAD deficiency, congenital malformations, and niacin supplementation.";
RL N. Engl. J. Med. 377:544-552(2017).
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}.
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 -!- 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};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03017};
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, ECO:0000269|PubMed:28792876}.
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 -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice were born at the
CC expected Mendelian ratio and are normal. They however show very high
CC levels of L-3-hydroxykynurenine compared to wild-type mice.
CC {ECO:0000269|PubMed:28792876}.
CC -!- SIMILARITY: Belongs to the kynureninase family. {ECO:0000255|HAMAP-
CC Rule:MF_03017}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB29386.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC34035.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK014484; BAB29386.2; ALT_INIT; mRNA.
DR EMBL; AK050024; BAC34035.1; ALT_INIT; mRNA.
DR CCDS; CCDS16018.1; -.
DR RefSeq; NP_001276522.1; NM_001289593.1.
DR RefSeq; NP_001276523.1; NM_001289594.1.
DR RefSeq; NP_081828.1; NM_027552.2.
DR RefSeq; XP_006498388.1; XM_006498325.3.
DR AlphaFoldDB; Q9CXF0; -.
DR SMR; Q9CXF0; -.
DR BioGRID; 214254; 2.
DR STRING; 10090.ENSMUSP00000028223; -.
DR iPTMnet; Q9CXF0; -.
DR PhosphoSitePlus; Q9CXF0; -.
DR SwissPalm; Q9CXF0; -.
DR jPOST; Q9CXF0; -.
DR MaxQB; Q9CXF0; -.
DR PaxDb; Q9CXF0; -.
DR PRIDE; Q9CXF0; -.
DR ProteomicsDB; 290005; -.
DR GeneID; 70789; -.
DR KEGG; mmu:70789; -.
DR CTD; 8942; -.
DR MGI; MGI:1918039; Kynu.
DR eggNOG; KOG3846; Eukaryota.
DR InParanoid; Q9CXF0; -.
DR OMA; TFPTDGY; -.
DR OrthoDB; 916879at2759; -.
DR Reactome; R-MMU-71240; Tryptophan catabolism.
DR UniPathway; UPA00253; UER00329.
DR UniPathway; UPA00334; UER00455.
DR BioGRID-ORCS; 70789; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Kynu; mouse.
DR PRO; PR:Q9CXF0; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9CXF0; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0061981; F:3-hydroxykynureninase activity; ISS:UniProtKB.
DR GO; GO:0030429; F:kynureninase activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0030170; F:pyridoxal phosphate binding; ISO:MGI.
DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IEA:UniProtKB-UniRule.
DR GO; GO:0043420; P:anthranilate metabolic process; ISO:MGI.
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:MGI.
DR GO; GO:0034341; P:response to interferon-gamma; ISO:MGI.
DR GO; GO:0034516; P:response to vitamin B6; ISO:MGI.
DR GO; GO:0006569; P:tryptophan catabolic process; ISO:MGI.
DR GO; GO:0019442; P:tryptophan catabolic process to acetyl-CoA; ISO:MGI.
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; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
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; Hydrolase; Pyridine nucleotide biosynthesis;
KW Pyridoxal phosphate; Reference proteome.
FT CHAIN 1..464
FT /note="Kynureninase"
FT /id="PRO_0000218658"
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:0000250|UniProtKB:Q16719, ECO:0000255|HAMAP-
FT Rule:MF_03017"
FT MOD_RES 276
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03017"
SQ SEQUENCE 464 AA; 52325 MW; FF51BE81F935E79E CRC64;
MEPSPLELPV DAVRRIAAEL NCDPTDERVA LRLDEEDKLS HFRNCFYIPK MRDLPSIDLS
LVSEDDDAIY FLGNSLGLQP KMVRTYLEEE LDKWAKMGAY GHDVGKRPWI VGDESIVSLM
KDIVGAHEKE IALMNALTIN LHLLLLSFFK PTPKRHKILL EAKAFPSDHY AIESQIQLHG
LDVEKSMRMV KPREGEETLR MEDILEVIEE EGDSIAVILF SGLHFYTGQL FNIPAITKAG
HAKGCFVGFD LAHAVGNVEL RLHDWGVDFA CWCSYKYLNS GAGGLAGAFV HEKHAHTVKP
ALVGWFGHDL STRFNMDNKL QLIPGANGFR ISNPPILLVC SLHASLEVFQ QATMTALRRK
SILLTGYLEY MLKHYHSKDN TENKGPIVNI ITPSRAEERG CQLTLTFSIP KKSVFKELEK
RGVVCDKREP DGIRVAPVPL YNSFHDVYKF IRLLTSILDS SERS
