ID   KMO_RAT                 Reviewed;         478 AA.
AC   O88867;
DT   04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   16-JUN-2009, entry version 55.
DE   RecName: Full=Kynurenine 3-monooxygenase;
DE            EC=1.14.13.9;
DE   AltName: Full=Kynurenine 3-hydroxylase;
GN   Name=Kmo;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Magagnin S., Covini N., Cini M., Bormetti R., Molinari A.,
RA   Speciale C., Post C., Benatti L.;
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Liver;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP   LOCATION, AND TISSUE SPECIFICITY.
RX   MEDLINE=93072878; PubMed=1332540; DOI=10.1016/0003-2697(92)90432-7;
RA   Erickson J.B., Flanagan E.M., Russo S., Reinhard J.F. Jr.;
RT   "A radiometric assay for kynurenine 3-hydroxylase based on the release
RT   of 3H2O during hydroxylation of L-[3,5-3H]kynurenine.";
RL   Anal. Biochem. 205:257-262(1992).
RN   [4]
RP   REVIEW.
RX   PubMed=12402501; DOI=10.1038/nrd870;
RA   Stone T.W., Darlington L.G.;
RT   "Endogenous kynurenines as targets for drug discovery and
RT   development.";
RL   Nat. Rev. Drug Discov. 1:609-620(2002).
CC   -!- FUNCTION: Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to
CC       form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of
CC       quinolinic acid, a neurotoxic NMDA receptor antagonist and
CC       potential endogenous inhibitor of NMDA receptor signaling in
CC       axonal targeting, synaptogenesis and apoptosis during brain
CC       development. Quinolinic acid may also affect NMDA receptor
CC       signaling in pancreatic beta cells, osteoblasts, myocardial cells,
CC       and the gastrointestinal tract (By similarity).
CC   -!- CATALYTIC ACTIVITY: L-kynurenine + NADPH + O(2) = 3-hydroxy-L-
CC       kynurenine + NADP(+) + H(2)O.
CC   -!- COFACTOR: FAD (By similarity).
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=11.3 uM for NADPH;
CC         KM=316 uM for NADH;
CC   -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; pyridine-2,3-
CC       dicarboxylate from L-kynurenine: step 1/3.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane; Multi-pass
CC       membrane protein.
CC   -!- TISSUE SPECIFICITY: Highest activity in liver and kidney. Low
CC       activity in spleen, stomach, intestinal tract, esophagus, heart
CC       and lung.
CC   -!- MISCELLANEOUS: Increased in neuroinflammatory conditions.
CC       Inhibitors are investigated as potential neuroprotective drugs
CC       since they lead to an increased level of kynurenic acid, a
CC       neuroprotective NMDA receptor agonist.
CC   -!- SIMILARITY: Belongs to the aromatic-ring hydroxylase family. KMO
CC       subfamily.
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DR   EMBL; AF056031; AAC62614.1; -; mRNA.
DR   EMBL; BC088142; AAH88142.1; -; mRNA.
DR   IPI; IPI00213422; -.
DR   RefSeq; NP_067604.1; -.
DR   UniGene; Rn.35029; -.
DR   PhosphoSite; O88867; -.
DR   PRIDE; O88867; -.
DR   Ensembl; ENSRNOG00000003709; Rattus norvegicus.
DR   GeneID; 59113; -.
DR   KEGG; rno:59113; -.
DR   NMPDR; fig|10116.3.peg.9628; -.
DR   RGD; 620610; Kmo.
DR   HOVERGEN; O88867; -.
DR   OMA; O88867; LHAIMPS.
DR   BRENDA; 1.14.13.9; 248.
DR   NextBio; 611759; -.
DR   ArrayExpress; O88867; -.
DR   GermOnline; ENSRNOG00000003709; Rattus norvegicus.
DR   GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR   GO; GO:0004502; F:kynurenine 3-monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0019674; P:NAD metabolic process; IDA:UniProtKB.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   GO; GO:0019363; P:pyridine nucleotide biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IDA:RGD.
DR   InterPro; IPR006076; FAD-dep_OxRdtase.
DR   InterPro; IPR003042; Rng_hydrolase-like.
DR   Pfam; PF01266; DAO; 1.
DR   PRINTS; PR00420; RNGMNOXGNASE.
PE   1: Evidence at protein level;
KW   FAD; Flavoprotein; Membrane; Mitochondrion;
KW   Mitochondrion outer membrane; Monooxygenase; NADP; Oxidoreductase;
KW   Phosphoprotein; Pyridine nucleotide biosynthesis; Transmembrane.
FT   CHAIN         1    478       Kynurenine 3-monooxygenase.
FT                                /FTId=PRO_0000229745.
FT   TRANSMEM    385    404       Potential.
FT   TRANSMEM    425    444       Potential.
FT   MOD_RES     399    399       Phosphothreonine (By similarity).
SQ   SEQUENCE   478 AA;  54353 MW;  72E775D1C05CFFAB CRC64;
     MASSDTEGKR VVVIGGGLVG ALNACFLAKR NFQVDVYEAR EDIRVANFMR GRSINLALSY
     RGRQALKAVG LEDQIVSKGV PMKARMIHSL SGKKSAIPYG NKSQYILSIS REKLNKDLLT
     AVESYPNAKV HFGHKLSKCC PEEGILTMLG PNKVPRDITC DLIVGCDGAY STVRAHLMKK
     PRFDYSQQYI PHGYMELTIP PKNGEYAMEP NCLHIWPRNA FMMIALPNMD KSFTCTLFMS
     FEEFEKLPTH SDVLDFFQKN FPDAIPLMGE QALMRDFFLL PAQPMISVKC SPFHLKSRCV
     LMGDAAHAIV PFFGQGMNAG FEDCLVFDEL MDKFNNDLSV CLPEFSRFRI PDDHAISDLS
     MYNYIEMRAH VNSRWFLFQR LLDKFLHALM PSTFIPLYTM VAFTRIRYHE AVLRWHWQKK
     VINRGLFVLG SLVAIGSAYI LVHHLSPRPL ELLRSAWTGT SGHWNRSADI SPRVPWSH
//