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MGP003603

UniProt Annotations

Entry Information
Gene Namekynurenine 3-monooxygenase (kynurenine 3-hydroxylase)
Protein EntryKMO_HUMAN
UniProt IDO15229
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1 {ECO:0000269|PubMed:10672018, ECO:0000269|PubMed:9237672}; IsoId=O15229-1; Sequence=Displayed; Name=2 {ECO:0000269|PubMed:16710414}; IsoId=O15229-2; Sequence=VSP_051973; Note=Gene model based on cDNA data. No experimental confirmation available. {ECO:0000305}; Name=3 {ECO:0000269|PubMed:16710414}; IsoId=O15229-3; Sequence=VSP_051972; Note=Gene model based on mouse cDNA data. No experimental confirmation available. {ECO:0000305};
Biophysicochemical PropertiesKinetic parameters: KM=24.1 uM for L-kynurenine {ECO:0000269|PubMed:10672018, ECO:0000269|PubMed:9237672}; Vmax=8.5 umol/min/mg enzyme {ECO:0000269|PubMed:10672018, ECO:0000269|PubMed:9237672}; pH dependence: Optimum pH is 7.5. {ECO:0000269|PubMed:10672018, ECO:0000269|PubMed:9237672};
Catalytic ActivityL-kynurenine + NADPH + O(2) = 3-hydroxy-L- kynurenine + NADP(+) + H(2)O. {ECO:0000255|HAMAP-Rule:MF_03018, ECO:0000269|PubMed:10672018, ECO:0000269|PubMed:9237672}.
CofactorName=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000255|HAMAP-Rule:MF_03018, ECO:0000269|PubMed:10672018};
FunctionCatalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid, a neurotoxic NMDA receptor antagonist and potential endogenous inhibitor of NMDA receptor signaling in axonal targeting, synaptogenesis and apoptosis during brain development. Quinolinic acid may also affect NMDA receptor signaling in pancreatic beta cells, osteoblasts, myocardial cells, and the gastrointestinal tract.
MiscellaneousIncreased in neuroinflammatory conditions. Inhibitors are investigated as potential neuroprotective drugs since they lead to an increased level of kynurenic acid, a neuroprotective NMDA receptor agonist. {ECO:0000269|PubMed:9237672}.
PathwayCofactor biosynthesis; NAD(+) biosynthesis; quinolinate from L-kynurenine: step 1/3. {ECO:0000255|HAMAP-Rule:MF_03018}.
SimilarityBelongs to the aromatic-ring hydroxylase family. KMO subfamily. {ECO:0000255|HAMAP-Rule:MF_03018}.
Subcellular LocationMitochondrion outer membrane {ECO:0000255|HAMAP-Rule:MF_03018, ECO:0000269|PubMed:9237672}; Multi-pass membrane protein {ECO:0000255|HAMAP-Rule:MF_03018, ECO:0000269|PubMed:9237672}.
Tissue SpecificityHighest levels in placenta and liver. Detectable in kidney. {ECO:0000269|PubMed:9237672}.
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