KMO_MOUSE
ID KMO_MOUSE Reviewed; 479 AA.
AC Q91WN4;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Kynurenine 3-monooxygenase {ECO:0000255|HAMAP-Rule:MF_03018};
DE EC=1.14.13.9 {ECO:0000255|HAMAP-Rule:MF_03018};
DE AltName: Full=Kynurenine 3-hydroxylase {ECO:0000255|HAMAP-Rule:MF_03018};
GN Name=Kmo {ECO:0000312|EMBL:AAH14683.1};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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] {ECO:0000305, ECO:0000312|EMBL:AAH14683.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH14683.1};
RC TISSUE=Liver {ECO:0000312|EMBL:AAH14683.1};
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, 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 [4]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=26752518; DOI=10.1038/nm.4020;
RA Mole D.J., Webster S.P., Uings I., Zheng X., Binnie M., Wilson K.,
RA Hutchinson J.P., Mirguet O., Walker A., Beaufils B., Ancellin N.,
RA Trottet L., Beneton V., Mowat C.G., Wilkinson M., Rowland P., Haslam C.,
RA McBride A., Homer N.Z., Baily J.E., Sharp M.G., Garden O.J., Hughes J.,
RA Howie S.E., Holmes D.S., Liddle J., Iredale J.P.;
RT "Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in
RT rodent models of acute pancreatitis.";
RL Nat. Med. 22:202-209(2016).
CC -!- FUNCTION: Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form
CC 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic
CC acid, a neurotoxic NMDA receptor antagonist and potential endogenous
CC inhibitor of NMDA receptor signaling in axonal targeting,
CC synaptogenesis and apoptosis during brain development. Quinolinic acid
CC may also affect NMDA receptor signaling in pancreatic beta cells,
CC osteoblasts, myocardial cells, and the gastrointestinal tract.
CC {ECO:0000255|HAMAP-Rule:MF_03018, ECO:0000269|PubMed:26752518}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine +
CC H2O + NADP(+); Xref=Rhea:RHEA:20545, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57959, ChEBI:CHEBI:58125, ChEBI:CHEBI:58349;
CC EC=1.14.13.9; Evidence={ECO:0000250|UniProtKB:O15229,
CC ECO:0000255|HAMAP-Rule:MF_03018, ECO:0000269|PubMed:26752518};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:O15229,
CC ECO:0000255|HAMAP-Rule:MF_03018};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from
CC L-kynurenine: step 1/3. {ECO:0000255|HAMAP-Rule:MF_03018}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000255|HAMAP-
CC Rule:MF_03018}; Multi-pass membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_03018}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15489334};
CC IsoId=Q91WN4-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:16141072};
CC IsoId=Q91WN4-2; Sequence=VSP_051974;
CC -!- TISSUE SPECIFICITY: Expressed by organs containing secondary lymphoid
CC tissue, such as the lung, spleen, mesenteric lymph node, thymus and
CC peripheral lymph nodes. {ECO:0000269|PubMed:26752518}.
CC -!- DOMAIN: Transmembrane domains are required for enzymatic activity.
CC {ECO:0000250|UniProtKB:O15229}.
CC -!- DISRUPTION PHENOTYPE: Mutants show normal fecundity, fertility and
CC longevity up tp 2 year. They have reduced serum 3-hydroxy-L-kynurenine
CC concentrations. They are protected against extrapancreatic tissue
CC injury to the lung, kidney and liver produced by acute pancreatitis-
CC induced multiple organ dysfunction syndrome.
CC {ECO:0000269|PubMed:26752518}.
CC -!- SIMILARITY: Belongs to the aromatic-ring hydroxylase family. KMO
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03018}.
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DR EMBL; AK129011; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC014683; AAH14683.1; -; mRNA.
DR CCDS; CCDS15548.1; -. [Q91WN4-1]
DR RefSeq; NP_598570.1; NM_133809.1. [Q91WN4-1]
DR AlphaFoldDB; Q91WN4; -.
DR SMR; Q91WN4; -.
DR STRING; 10090.ENSMUSP00000038914; -.
DR BindingDB; Q91WN4; -.
DR ChEMBL; CHEMBL3407318; -.
DR iPTMnet; Q91WN4; -.
DR PhosphoSitePlus; Q91WN4; -.
DR SwissPalm; Q91WN4; -.
DR EPD; Q91WN4; -.
DR jPOST; Q91WN4; -.
DR MaxQB; Q91WN4; -.
DR PaxDb; Q91WN4; -.
DR PeptideAtlas; Q91WN4; -.
DR PRIDE; Q91WN4; -.
DR ProteomicsDB; 265014; -. [Q91WN4-1]
DR ProteomicsDB; 265015; -. [Q91WN4-2]
DR Antibodypedia; 34702; 200 antibodies from 31 providers.
DR DNASU; 98256; -.
DR Ensembl; ENSMUST00000040250; ENSMUSP00000038914; ENSMUSG00000039783. [Q91WN4-1]
DR Ensembl; ENSMUST00000097458; ENSMUSP00000095067; ENSMUSG00000039783. [Q91WN4-2]
DR GeneID; 98256; -.
DR KEGG; mmu:98256; -.
DR UCSC; uc007dto.1; mouse. [Q91WN4-1]
DR UCSC; uc011wxd.1; mouse. [Q91WN4-2]
DR CTD; 8564; -.
DR MGI; MGI:2138151; Kmo.
DR VEuPathDB; HostDB:ENSMUSG00000039783; -.
DR eggNOG; KOG2614; Eukaryota.
DR GeneTree; ENSGT00390000000747; -.
DR HOGENOM; CLU_023210_0_0_1; -.
DR InParanoid; Q91WN4; -.
DR OMA; REFMFIA; -.
DR OrthoDB; 462247at2759; -.
DR PhylomeDB; Q91WN4; -.
DR TreeFam; TF312990; -.
DR BRENDA; 1.14.13.9; 3474.
DR Reactome; R-MMU-71240; Tryptophan catabolism.
DR UniPathway; UPA00253; UER00328.
DR BioGRID-ORCS; 98256; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Kmo; mouse.
DR PRO; PR:Q91WN4; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q91WN4; protein.
DR Bgee; ENSMUSG00000039783; Expressed in left lobe of liver and 59 other tissues.
DR ExpressionAtlas; Q91WN4; baseline and differential.
DR Genevisible; Q91WN4; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:MGI.
DR GO; GO:0004502; F:kynurenine 3-monooxygenase activity; IMP:UniProtKB.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; ISS:UniProtKB.
DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IEA:UniProtKB-UniRule.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0043420; P:anthranilate metabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0034276; P:kynurenic acid biosynthetic process; ISO:MGI.
DR GO; GO:0070189; P:kynurenine metabolic process; IMP:UniProtKB.
DR GO; GO:0097052; P:L-kynurenine metabolic process; ISO:MGI.
DR GO; GO:0019674; P:NAD metabolic process; ISS:UniProtKB.
DR GO; GO:0014049; P:positive regulation of glutamate secretion; ISO:MGI.
DR GO; GO:1903296; P:positive regulation of glutamate secretion, neurotransmission; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0019805; P:quinolinate biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0009651; P:response to salt stress; ISO:MGI.
DR GO; GO:0006569; P:tryptophan catabolic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.50.50.60; -; 1.
DR HAMAP; MF_01971; Kynurenine_monooxygenase; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR027545; Kynurenine_monooxygenase.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; FAD; Flavoprotein; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Monooxygenase; NADP; Oxidoreductase;
KW Pyridine nucleotide biosynthesis; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..479
FT /note="Kynurenine 3-monooxygenase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000229743"
FT TRANSMEM 385..404
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03018"
FT TRANSMEM 425..445
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03018"
FT BINDING 19
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 37..40
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 57
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 85
FT /ligand="L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:57959"
FT /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT BINDING 99
FT /ligand="L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:57959"
FT /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT BINDING 111
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 136
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 172
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 304
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 317..318
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:O15229"
FT BINDING 363
FT /ligand="L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:57959"
FT /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT BINDING 398
FT /ligand="L-kynurenine"
FT /ligand_id="ChEBI:CHEBI:57959"
FT /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT VAR_SEQ 367..400
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_051974"
SQ SEQUENCE 479 AA; 54532 MW; E880997DBC9C8163 CRC64;
MASSDTQGKR VAVIGGGLVG ALNACFLAKR NFQVDVYEAR EDIRVAKSAR GRSINLALSY
RGRQALKAIG LEDQIVSKGV PMKARMIHSL SGKKSAIPYG NKSQYILSIS RENLNKDLLT
AVESYANAKV HFGHKLSKCI PEEGVLTVLG PDKVPRDVTC DLVVGCDGAY STVRAHLMKK
PRFDYTQQYI PHGYMELTIP PKNGEYAMEP NCLHIWPRNA YMMIALPNMD KSFTCTLFMP
FEEFERLPTR SDVLDFFQKN FPDAIPLMGE QALMRDFFLL PAQPMISVKC SPFHLKSHCV
LMGDAAHAIV PFFGQGMNAG FEDCLVFDEL MDKFNNNLSM CLPEFSRFRI PDDHAISDLS
MYNYIEMRAH VNSRWFLFQK LLDKFLHAIM PSTFIPLYTM VAFTRIRYHE AVLRWHWQKK
VINRGLFVLG SLIAIGGTYL LVHHLSLRPL EFLRRPAWMG TTGYWTRSTD ISLQVPWSY
