KYNU_HUMAN
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 03-AUG-2022, entry version 190.
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, 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=3.0 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 PDBsum; 2HZP; -.
DR PDBsum; 3E9K; -.
DR AlphaFoldDB; Q16719; -.
DR SMR; Q16719; -.
DR BioGRID; 114454; 71.
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; Q16719; -.
DR PeptideAtlas; Q16719; -.
DR PRIDE; Q16719; -.
DR ProteomicsDB; 61040; -. [Q16719-1]
DR ProteomicsDB; 61041; -. [Q16719-2]
DR Antibodypedia; 33609; 370 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 CTD; 8942; -.
DR DisGeNET; 8942; -.
DR GeneCards; 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; TFPTDGY; -.
DR OrthoDB; 916879at2759; -.
DR PhylomeDB; Q16719; -.
DR TreeFam; TF300707; -.
DR BioCyc; MetaCyc:HS03952-MON; -.
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; 21 hits in 1086 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 154 other tissues.
DR ExpressionAtlas; Q16719; baseline and differential.
DR Genevisible; Q16719; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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 interferon-gamma; 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; 3.40.640.10; -; 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 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 3-
FT 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 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
