ID   KYNU_HUMAN              Reviewed;         465 AA.
AC   Q16719; B2RCZ5; D3DP79; Q6I9T2; Q9BVW3;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 199.
DE   RecName: Full=Kynureninase {ECO:0000255|HAMAP-Rule:MF_03017};
DE            EC=3.7.1.3 {ECO:0000255|HAMAP-Rule:MF_03017, ECO:0000269|PubMed:11985583, ECO:0000269|PubMed:17300176, ECO:0000269|PubMed:8706755, ECO:0000269|PubMed:9180257};
DE   AltName: Full=L-kynurenine hydrolase {ECO:0000255|HAMAP-Rule:MF_03017};
GN   Name=KYNU {ECO:0000255|HAMAP-Rule:MF_03017,
GN   ECO:0000312|HGNC:HGNC:6469};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP   TISSUE SPECIFICITY, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RC   TISSUE=Hepatoma;
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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] (ISOFORM 1), AND VARIANT GLU-412.
RC   TISSUE=Synovium;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Cervix;
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   [8]
RP   MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=11985583; DOI=10.1046/j.1432-1033.2002.02854.x;
RA   Walsh H.A., Botting N.P.;
RT   "Purification and biochemical characterization of some of the properties of
RT   recombinant human kynureninase.";
RL   Eur. J. Biochem. 269:2069-2074(2002).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [10]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [11]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE,
RP   HOMODIMERIZATION, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=17300176; DOI=10.1021/bi0616697;
RA   Lima S., Khristoforov R., Momany C., Phillips R.S.;
RT   "Crystal structure of Homo sapiens kynureninase.";
RL   Biochemistry 46:2735-2744(2007).
RN   [13]
RP   INVOLVEMENT IN HYXKY, AND VARIANT HYXKY ALA-198.
RX   PubMed=17334708; DOI=10.1007/s10545-007-0396-2;
RA   Christensen M., Duno M., Lund A.M., Skovby F., Christensen E.;
RT   "Xanthurenic aciduria due to a mutation in KYNU encoding kynureninase.";
RL   J. Inherit. Metab. Dis. 30:248-255(2007).
RN   [14]
RP   INVOLVEMENT IN VCRL2, VARIANT VCRL2 156-TYR--ASN-465 DEL, FUNCTION,
RP   CATALYTIC ACTIVITY, PATHWAY, CHARACTERIZATION OF VARIANT VCRL2
RP   156-TYR--ASN-465 DEL, AND CHARACTERIZATION OF VARIANT HYXKY ALA-198.
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:0000269|PubMed:11985583, ECO:0000269|PubMed:17300176,
CC       ECO:0000269|PubMed:28792876, ECO:0000269|PubMed:8706755,
CC       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:11985583, ECO:0000269|PubMed:17300176,
CC         ECO:0000269|PubMed:8706755, 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:11985583,
CC         ECO:0000269|PubMed:17300176, ECO:0000269|PubMed:28792876,
CC         ECO:0000269|PubMed:8706755, ECO:0000269|PubMed:9180257};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000269|PubMed:17300176};
CC   -!- ACTIVITY REGULATION: Inhibited by o-methoxybenzoylalanine (OMBA).
CC       {ECO:0000269|PubMed:8706755, ECO:0000269|PubMed:9180257}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=493 uM for L-kynurenine (at pH 7.0) {ECO:0000269|PubMed:11985583,
CC         ECO:0000269|PubMed:17300176, ECO:0000269|PubMed:8706755,
CC         ECO:0000269|PubMed:9180257};
CC         KM=28.3 uM for DL-3-hydroxykynurenine (at pH 7.0)
CC         {ECO:0000269|PubMed:11985583, ECO:0000269|PubMed:17300176,
CC         ECO:0000269|PubMed:8706755, ECO:0000269|PubMed:9180257};
CC         KM=3 uM for DL-3-hydroxykynurenine (at pH 7.9)
CC         {ECO:0000269|PubMed:11985583, ECO:0000269|PubMed:17300176,
CC         ECO:0000269|PubMed:8706755, ECO:0000269|PubMed:9180257};
CC       pH dependence:
CC         Optimum pH is 8.25 with DL-3-hydroxykynurenine as substrate.
CC         {ECO:0000269|PubMed:11985583, ECO:0000269|PubMed:17300176,
CC         ECO:0000269|PubMed:8706755, 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       ECO:0000269|PubMed:28792876}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03017,
CC       ECO:0000269|PubMed:17300176}.
CC   -!- INTERACTION:
CC       Q16719-2; Q8WUE5: CT55; NbExp=3; IntAct=EBI-12351611, EBI-6873363;
CC       Q16719-2; P56545-3: CTBP2; NbExp=3; IntAct=EBI-12351611, EBI-10171902;
CC       Q16719-2; Q9NVL1-2: FAM86C1P; NbExp=3; IntAct=EBI-12351611, EBI-12845222;
CC       Q16719-2; P61968: LMO4; NbExp=3; IntAct=EBI-12351611, EBI-2798728;
CC       Q16719-2; P59942: MCCD1; NbExp=3; IntAct=EBI-12351611, EBI-11987923;
CC       Q16719-2; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-12351611, EBI-5662487;
CC       Q16719-2; P78356-2: PIP4K2B; NbExp=3; IntAct=EBI-12351611, EBI-11532361;
CC       Q16719-2; Q86WH2: RASSF3; NbExp=3; IntAct=EBI-12351611, EBI-2845202;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000255|HAMAP-
CC       Rule:MF_03017, ECO:0000269|PubMed:8706755}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q16719-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q16719-2; Sequence=VSP_042739, VSP_042740;
CC   -!- TISSUE SPECIFICITY: Expressed in all tissues tested (heart, brain
CC       placenta, lung, liver, skeletal muscle, kidney and pancreas). Highest
CC       levels found in placenta, liver and lung. Expressed in all brain
CC       regions. {ECO:0000269|PubMed:8706755, ECO:0000269|PubMed:9180257}.
CC   -!- INDUCTION: Increased levels in several cerebral and systemic
CC       inflammatory conditions.
CC   -!- MASS SPECTROMETRY: Mass=52400; Method=MALDI; Note=The reported mass is
CC       given to only three significant figures.;
CC       Evidence={ECO:0000269|PubMed:11985583};
CC   -!- DISEASE: Hydroxykynureninuria (HYXKY) [MIM:236800]: An inborn error of
CC       amino acid metabolism characterized by massive urinary excretion of
CC       large amounts of kynurenine, 3-hydroxykynurenine and xanthurenic acid.
CC       Affected individuals manifest renal tubular dysfunction, metabolic
CC       acidosis, psychomotor retardation, non-progressive encephalopathy, and
CC       muscular hypertonia. {ECO:0000269|PubMed:17334708,
CC       ECO:0000269|PubMed:28792876}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Vertebral, cardiac, renal, and limb defects syndrome 2 (VCRL2)
CC       [MIM:617661]: An autosomal recessive congenital malformation syndrome
CC       characterized by vertebral segmentation abnormalities, congenital
CC       cardiac defects, renal defects, and distal mild limb defects.
CC       {ECO:0000269|PubMed:28792876}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the kynureninase family. {ECO:0000255|HAMAP-
CC       Rule:MF_03017}.
CC   -!- CAUTION: It has been reported that this enzyme possesses no measurable
CC       activity against L-kynurenine and is subject to inhibition by both L-
CC       kynurenine and D-kynurenine at pH 7.9. {ECO:0000305|PubMed:11985583}.
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DR   EMBL; U57721; AAC50650.1; -; mRNA.
DR   EMBL; AK315343; BAG37742.1; -; mRNA.
DR   EMBL; CR457423; CAG33704.1; -; mRNA.
DR   EMBL; AC013437; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC013444; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471058; EAX11599.1; -; Genomic_DNA.
DR   EMBL; CH471058; EAX11600.1; -; Genomic_DNA.
DR   EMBL; CH471058; EAX11601.1; -; Genomic_DNA.
DR   EMBL; BC000879; AAH00879.1; -; mRNA.
DR   CCDS; CCDS2183.1; -. [Q16719-1]
DR   CCDS; CCDS33299.1; -. [Q16719-2]
DR   PIR; G02652; G02652.
DR   RefSeq; NP_001028170.1; NM_001032998.1. [Q16719-2]
DR   RefSeq; NP_001186170.1; NM_001199241.1. [Q16719-1]
DR   RefSeq; NP_003928.1; NM_003937.2. [Q16719-1]
DR   RefSeq; XP_016860706.1; XM_017005217.1. [Q16719-2]
DR   PDB; 2HZP; X-ray; 2.00 A; A=1-465.
DR   PDB; 3E9K; X-ray; 1.70 A; A=1-465.
DR   PDB; 7S3V; X-ray; 3.25 A; A/B=1-465.
DR   PDBsum; 2HZP; -.
DR   PDBsum; 3E9K; -.
DR   PDBsum; 7S3V; -.
DR   AlphaFoldDB; Q16719; -.
DR   SMR; Q16719; -.
DR   BioGRID; 114454; 75.
DR   IntAct; Q16719; 12.
DR   STRING; 9606.ENSP00000264170; -.
DR   BindingDB; Q16719; -.
DR   ChEMBL; CHEMBL5100; -.
DR   DrugBank; DB00160; Alanine.
DR   DrugBank; DB07069; m-Hydroxyhippuric acid.
DR   DrugBank; DB00114; Pyridoxal phosphate.
DR   GlyGen; Q16719; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q16719; -.
DR   PhosphoSitePlus; Q16719; -.
DR   SwissPalm; Q16719; -.
DR   BioMuta; KYNU; -.
DR   DMDM; 3913982; -.
DR   EPD; Q16719; -.
DR   jPOST; Q16719; -.
DR   MassIVE; Q16719; -.
DR   MaxQB; Q16719; -.
DR   PaxDb; 9606-ENSP00000264170; -.
DR   PeptideAtlas; Q16719; -.
DR   ProteomicsDB; 61040; -. [Q16719-1]
DR   ProteomicsDB; 61041; -. [Q16719-2]
DR   Pumba; Q16719; -.
DR   Antibodypedia; 33609; 407 antibodies from 33 providers.
DR   DNASU; 8942; -.
DR   Ensembl; ENST00000264170.9; ENSP00000264170.4; ENSG00000115919.15. [Q16719-1]
DR   Ensembl; ENST00000375773.6; ENSP00000364928.2; ENSG00000115919.15. [Q16719-2]
DR   Ensembl; ENST00000409512.5; ENSP00000386731.1; ENSG00000115919.15. [Q16719-1]
DR   GeneID; 8942; -.
DR   KEGG; hsa:8942; -.
DR   MANE-Select; ENST00000264170.9; ENSP00000264170.4; NM_003937.3; NP_003928.1.
DR   UCSC; uc002tvk.4; human. [Q16719-1]
DR   AGR; HGNC:6469; -.
DR   CTD; 8942; -.
DR   DisGeNET; 8942; -.
DR   GeneCards; KYNU; -.
DR   GeneReviews; KYNU; -.
DR   HGNC; HGNC:6469; KYNU.
DR   HPA; ENSG00000115919; Tissue enhanced (liver, urinary bladder).
DR   MalaCards; KYNU; -.
DR   MIM; 236800; phenotype.
DR   MIM; 605197; gene.
DR   MIM; 617661; phenotype.
DR   neXtProt; NX_Q16719; -.
DR   OpenTargets; ENSG00000115919; -.
DR   Orphanet; 521438; Congenital vertebral-cardiac-renal anomalies syndrome.
DR   Orphanet; 79155; Hydroxykynureninuria.
DR   PharmGKB; PA30258; -.
DR   VEuPathDB; HostDB:ENSG00000115919; -.
DR   eggNOG; KOG3846; Eukaryota.
DR   GeneTree; ENSGT00390000008033; -.
DR   HOGENOM; CLU_003433_4_0_1; -.
DR   InParanoid; Q16719; -.
DR   OMA; LPGWNSH; -.
DR   OrthoDB; 5471916at2759; -.
DR   PhylomeDB; Q16719; -.
DR   TreeFam; TF300707; -.
DR   BioCyc; MetaCyc:HS03952-MONOMER; -.
DR   BRENDA; 3.7.1.3; 2681.
DR   PathwayCommons; Q16719; -.
DR   Reactome; R-HSA-71240; Tryptophan catabolism.
DR   SABIO-RK; Q16719; -.
DR   SignaLink; Q16719; -.
DR   UniPathway; UPA00253; UER00329.
DR   UniPathway; UPA00334; UER00455.
DR   BioGRID-ORCS; 8942; 23 hits in 1164 CRISPR screens.
DR   ChiTaRS; KYNU; human.
DR   EvolutionaryTrace; Q16719; -.
DR   GeneWiki; Kynureninase; -.
DR   GenomeRNAi; 8942; -.
DR   Pharos; Q16719; Tchem.
DR   PRO; PR:Q16719; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q16719; Protein.
DR   Bgee; ENSG00000115919; Expressed in endometrium epithelium and 156 other cell types or tissues.
DR   ExpressionAtlas; Q16719; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0061981; F:3-hydroxykynureninase activity; IDA:UniProtKB.
DR   GO; GO:0030429; F:kynureninase activity; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IEA:UniProtKB-UniRule.
DR   GO; GO:0043420; P:anthranilate metabolic process; IDA:UniProtKB.
DR   GO; GO:0097053; P:L-kynurenine catabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0009435; P:NAD biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0019805; P:quinolinate biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0034341; P:response to type II interferon; IDA:UniProtKB.
DR   GO; GO:0034516; P:response to vitamin B6; IMP:UniProtKB.
DR   GO; GO:0006569; P:tryptophan catabolic process; IMP:UniProtKB.
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; Q16719; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW   Disease variant; Hydrolase; Pyridine nucleotide biosynthesis;
KW   Pyridoxal phosphate; Reference proteome.
FT   CHAIN           1..465
FT                   /note="Kynureninase"
FT                   /id="PRO_0000218657"
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                   ECO:0000269|PubMed:17300176"
FT   BINDING         165..168
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
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                   ECO:0000269|PubMed:17300176"
FT   BINDING         253
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017,
FT                   ECO:0000269|PubMed:17300176"
FT   BINDING         275
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017,
FT                   ECO:0000269|PubMed:17300176"
FT   BINDING         305
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017,
FT                   ECO:0000269|PubMed:17300176"
FT   BINDING         333
FT                   /ligand="pyridoxal 5'-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:597326"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03017,
FT                   ECO:0000269|PubMed:17300176"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   MOD_RES         276
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT   VAR_SEQ         302..307
FT                   /note="LVGWFG -> RSEFFN (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_042739"
FT   VAR_SEQ         308..465
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_042740"
FT   VARIANT         156..465
FT                   /note="Missing (in VCRL2; strongly reduced
FT                   3-hydroxykynureninase activity)"
FT                   /evidence="ECO:0000269|PubMed:28792876"
FT                   /id="VAR_080254"
FT   VARIANT         188
FT                   /note="R -> Q (in dbSNP:rs2304705)"
FT                   /id="VAR_049724"
FT   VARIANT         198
FT                   /note="T -> A (in HYXKY; reduced 3-hydroxykynureninase
FT                   activity; dbSNP:rs606231307)"
FT                   /evidence="ECO:0000269|PubMed:17334708,
FT                   ECO:0000269|PubMed:28792876"
FT                   /id="VAR_054401"
FT   VARIANT         412
FT                   /note="K -> E (in dbSNP:rs9013)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_022092"
FT   HELIX           9..20
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           27..35
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           40..45
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           51..53
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           59..61
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   TURN            73..75
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           83..97
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           98..102
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          104..107
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           109..111
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           114..117
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           118..120
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           121..124
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           128..130
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          131..133
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           137..148
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          153..155
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          157..161
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           166..178
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           183..186
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          187..190
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           201..211
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           212..214
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          215..223
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   TURN            225..227
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           233..242
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          246..250
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   TURN            252..257
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           262..265
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          269..272
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          274..276
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          287..290
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           292..294
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   TURN            295..297
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           305..307
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           310..313
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           326..329
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           336..352
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           354..375
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          388..390
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           396..398
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          403..407
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          410..412
FT                   /evidence="ECO:0007829|PDB:7S3V"
FT   HELIX           414..419
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   TURN            420..422
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          426..428
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   TURN            429..431
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   STRAND          432..436
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   TURN            439..441
FT                   /evidence="ECO:0007829|PDB:3E9K"
FT   HELIX           444..458
FT                   /evidence="ECO:0007829|PDB:3E9K"
SQ   SEQUENCE   465 AA;  52352 MW;  BDD136BE18C79EBB CRC64;
     MEPSSLELPA DTVQRIAAEL KCHPTDERVA LHLDEEDKLR HFRECFYIPK IQDLPPVDLS
     LVNKDENAIY FLGNSLGLQP KMVKTYLEEE LDKWAKIAAY GHEVGKRPWI TGDESIVGLM
     KDIVGANEKE IALMNALTVN LHLLMLSFFK PTPKRYKILL EAKAFPSDHY AIESQLQLHG
     LNIEESMRMI KPREGEETLR IEDILEVIEK EGDSIAVILF SGVHFYTGQH FNIPAITKAG
     QAKGCYVGFD LAHAVGNVEL YLHDWGVDFA CWCSYKYLNA GAGGIAGAFI HEKHAHTIKP
     ALVGWFGHEL STRFKMDNKL QLIPGVCGFR ISNPPILLVC SLHASLEIFK QATMKALRKK
     SVLLTGYLEY LIKHNYGKDK AATKKPVVNI ITPSHVEERG CQLTITFSVP NKDVFQELEK
     RGVVCDKRNP NGIRVAPVPL YNSFHDVYKF TNLLTSILDS AETKN
//