UniProtKB - O15229 (KMO_HUMAN)
Protein
Kynurenine 3-monooxygenase
Gene
KMO
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn) (PubMed:29429898, PubMed:23575632, PubMed:26752518, PubMed:28604669, PubMed:29208702). 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 (Probable).1 Publication5 Publications
Miscellaneous
Increased 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.1 Publication
Catalytic activityi
- H+ + L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine + H2O + NADP+UniRule annotation3 PublicationsEC:1.14.13.9UniRule annotation3 Publications
Cofactori
FADUniRule annotation2 Publications
Kineticsi
Kcat is 0.24 sec(-1) for L-kynurenine.1 Publication
- KM=24.1 µM for L-kynurenine3 Publications
- KM=2 µM for L-kynurenine1 Publication
- KM=78 µM for L-kynurenine1 Publication
- Vmax=8.5 µmol/min/mg enzyme2 Publications
pH dependencei
Optimum pH is 7.5.2 Publications
: NAD(+) biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes quinolinate from L-kynurenine.UniRule annotationProteins known to be involved in the 3 steps of the subpathway in this organism are:
- Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO)
- Kynureninase (KYNU), Kynureninase (KYNU), Kynureninase (KYNU)
- 3-hydroxyanthranilate 3,4-dioxygenase (HAAO)
View all proteins of this organism that are known to be involved in the subpathway that synthesizes quinolinate from L-kynurenine, the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 19 | FAD; via amide nitrogenCombined sources1 Publication | 1 | |
Binding sitei | 57 | FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication | 1 | |
Binding sitei | 85 | L-kynurenineBy similarity | 1 | |
Binding sitei | 99 | L-kynurenineBy similarity | 1 | |
Binding sitei | 111 | FADCombined sources1 Publication | 1 | |
Binding sitei | 136 | FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication | 1 | |
Binding sitei | 172 | FADCombined sources1 Publication | 1 | |
Binding sitei | 304 | FAD; via amide nitrogenCombined sources1 Publication | 1 | |
Binding sitei | 363 | L-kynurenineBy similarity | 1 | |
Binding sitei | 398 | L-kynurenineBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 37 – 40 | FADCombined sources1 Publication | 4 | |
Nucleotide bindingi | 317 – 318 | FADCombined sources1 Publication | 2 |
GO - Molecular functioni
- FAD binding Source: UniProtKB
- flavin adenine dinucleotide binding Source: UniProtKB
- kynurenine 3-monooxygenase activity Source: UniProtKB
- NAD(P)H oxidase (H(2)O(2)-forming activity Source: UniProtKB
GO - Biological processi
- 'de novo' NAD biosynthetic process from tryptophan Source: UniProtKB-UniRule
- aging Source: Ensembl
- anthranilate metabolic process Source: UniProtKB-UniRule
- cellular response to interleukin-1 Source: Ensembl
- cellular response to lipopolysaccharide Source: Ensembl
- kynurenic acid biosynthetic process Source: Ensembl
- kynurenine metabolic process Source: UniProtKB
- L-kynurenine metabolic process Source: Ensembl
- NAD metabolic process Source: UniProtKB
- positive regulation of glutamate secretion, neurotransmission Source: Ensembl
- positive regulation of neuron death Source: Ensembl
- quinolinate biosynthetic process Source: UniProtKB-UniRule
- response to salt stress Source: UniProtKB
- tryptophan catabolic process Source: Reactome
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Pyridine nucleotide biosynthesis |
Ligand | FAD, Flavoprotein, NADP |
Enzyme and pathway databases
BioCyci | MetaCyc:HS04082-MONOMER |
PathwayCommonsi | O15229 |
Reactomei | R-HSA-71240, Tryptophan catabolism |
SABIO-RKi | O15229 |
UniPathwayi | UPA00253;UER00328 |
Names & Taxonomyi
Protein namesi | Recommended name: Kynurenine 3-monooxygenaseUniRule annotation (EC:1.14.13.9UniRule annotation)Alternative name(s): Kynurenine 3-hydroxylaseUniRule annotation |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000117009.11 |
HGNCi | HGNC:6381, KMO |
MIMi | 603538, gene |
neXtProti | NX_O15229 |
Subcellular locationi
Mitochondrion
- Mitochondrion outer membrane UniRule annotation1 Publication; Multi-pass membrane protein UniRule annotation1 Publication
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular space Source: Ensembl
Mitochondrion
- mitochondrial outer membrane Source: UniProtKB
- mitochondrion Source: GO_Central
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 385 – 404 | HelicalUniRule annotationAdd BLAST | 20 | |
Transmembranei | 425 – 445 | HelicalUniRule annotationAdd BLAST | 21 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion outer membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 85 | R → A or K: Abolishes kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 99 | Y → A: Abolishes kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 99 | Y → F: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 312 – 313 | FF → AA: Abolishes NADPH oxidase activity. 1 Publication | 2 | |
Mutagenesisi | 312 | F → A: Decreases to 30% NADPH oxidase activity. 1 Publication | 1 | |
Mutagenesisi | 313 | F → A: Decreases to 50% NADPH oxidase activity. 1 Publication | 1 | |
Mutagenesisi | 363 | N → A: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 363 | N → D: Abolishes kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 366 | E → A or Q: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 367 | M → A: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 367 | M → L: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 398 | Y → A or F: Abolishes kynurenine 3-monooxygenase activity. 1 Publication | 1 | |
Mutagenesisi | 465 | N → A: Not glycosylted. Reduces to 80% kynurenine 3-monooxygenase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8564 |
OpenTargetsi | ENSG00000117009 |
PharmGKBi | PA30172 |
Miscellaneous databases
Pharosi | O15229, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2145 |
GuidetoPHARMACOLOGYi | 2886 |
Polymorphism and mutation databases
BioMutai | KMO |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000229742 | 1 – 486 | Kynurenine 3-monooxygenaseCuratedAdd BLAST | 486 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 465 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | O15229 |
MassIVEi | O15229 |
MaxQBi | O15229 |
PaxDbi | O15229 |
PeptideAtlasi | O15229 |
PRIDEi | O15229 |
ProteomicsDBi | 48519 [O15229-1] 48520 [O15229-2] 48521 [O15229-3] |
PTM databases
GlyGeni | O15229, 1 site |
iPTMneti | O15229 |
PhosphoSitePlusi | O15229 |
Expressioni
Tissue specificityi
Highest levels in placenta and liver. Detectable in kidney.1 Publication
Gene expression databases
Bgeei | ENSG00000117009, Expressed in placenta and 148 other tissues |
ExpressionAtlasi | O15229, baseline and differential |
Genevisiblei | O15229, HS |
Organism-specific databases
HPAi | ENSG00000117009, Tissue enhanced (blood, liver, placenta) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 114133, 5 interactors |
IntActi | O15229, 2 interactors |
STRINGi | 9606.ENSP00000355517 |
Chemistry databases
BindingDBi | O15229 |
Miscellaneous databases
RNActi | O15229, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O15229 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
Transmembrane domains are required for enzymatic activity.2 Publications
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2614, Eukaryota |
GeneTreei | ENSGT00390000000747 |
HOGENOMi | CLU_023210_0_0_1 |
InParanoidi | O15229 |
OMAi | NLAMSNR |
OrthoDBi | 462247at2759 |
PhylomeDBi | O15229 |
TreeFami | TF312990 |
Family and domain databases
Gene3Di | 3.50.50.60, 1 hit |
HAMAPi | MF_01971, Kynurenine_monooxygenase, 1 hit |
InterProi | View protein in InterPro IPR002938, FAD-bd IPR036188, FAD/NAD-bd_sf IPR027545, Kynurenine_monooxygenase |
Pfami | View protein in Pfam PF01494, FAD_binding_3, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 12 Publications (identifier: O15229-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDSSVIQRKK VAVIGGGLVG SLQACFLAKR NFQIDVYEAR EDTRVATFTR
60 70 80 90 100
GRSINLALSH RGRQALKAVG LEDQIVSQGI PMRARMIHSL SGKKSAIPYG
110 120 130 140 150
TKSQYILSVS RENLNKDLLT AAEKYPNVKM HFNHRLLKCN PEEGMITVLG
160 170 180 190 200
SDKVPKDVTC DLIVGCDGAY STVRSHLMKK PRFDYSQQYI PHGYMELTIP
210 220 230 240 250
PKNGDYAMEP NYLHIWPRNT FMMIALPNMN KSFTCTLFMP FEEFEKLLTS
260 270 280 290 300
NDVVDFFQKY FPDAIPLIGE KLLVQDFFLL PAQPMISVKC SSFHFKSHCV
310 320 330 340 350
LLGDAAHAIV PFFGQGMNAG FEDCLVFDEL MDKFSNDLSL CLPVFSRLRI
360 370 380 390 400
PDDHAISDLS MYNYIEMRAH VNSSWFIFQK NMERFLHAIM PSTFIPLYTM
410 420 430 440 450
VTFSRIRYHE AVQRWHWQKK VINKGLFFLG SLIAISSTYL LIHYMSPRSF
460 470 480
LRLRRPWNWI AHFRNTTCFP AKAVDSLEQI SNLISR
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH0Y320 | H0Y320_HUMAN | Kynurenine 3-monooxygenase | KMO | 182 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030845 | 452 | R → C2 PublicationsCorresponds to variant dbSNP:rs1053230Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_051972 | 367 – 400 | Missing in isoform 3. 1 PublicationAdd BLAST | 34 | |
Alternative sequenceiVSP_051973 | 367 – 379 | Missing in isoform 2. 1 PublicationAdd BLAST | 13 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y13153 mRNA Translation: CAA73613.1 AF056032 mRNA Translation: AAC62615.1 AL133390 Genomic DNA No translation available. FO393423 Genomic DNA No translation available. |
CCDSi | CCDS1618.1 [O15229-1] |
RefSeqi | NP_003670.2, NM_003679.4 [O15229-1] |
Genome annotation databases
Ensembli | ENST00000366557; ENSP00000355515; ENSG00000117009 [O15229-3] ENST00000366558; ENSP00000355516; ENSG00000117009 [O15229-2] ENST00000366559; ENSP00000355517; ENSG00000117009 [O15229-1] |
GeneIDi | 8564 |
KEGGi | hsa:8564 |
UCSCi | uc001hyy.4, human [O15229-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y13153 mRNA Translation: CAA73613.1 AF056032 mRNA Translation: AAC62615.1 AL133390 Genomic DNA No translation available. FO393423 Genomic DNA No translation available. |
CCDSi | CCDS1618.1 [O15229-1] |
RefSeqi | NP_003670.2, NM_003679.4 [O15229-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5X68 | X-ray | 2.10 | A/B | 1-374 | [»] | |
SMRi | O15229 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114133, 5 interactors |
IntActi | O15229, 2 interactors |
STRINGi | 9606.ENSP00000355517 |
Chemistry databases
BindingDBi | O15229 |
ChEMBLi | CHEMBL2145 |
GuidetoPHARMACOLOGYi | 2886 |
PTM databases
GlyGeni | O15229, 1 site |
iPTMneti | O15229 |
PhosphoSitePlusi | O15229 |
Polymorphism and mutation databases
BioMutai | KMO |
Proteomic databases
jPOSTi | O15229 |
MassIVEi | O15229 |
MaxQBi | O15229 |
PaxDbi | O15229 |
PeptideAtlasi | O15229 |
PRIDEi | O15229 |
ProteomicsDBi | 48519 [O15229-1] 48520 [O15229-2] 48521 [O15229-3] |
Protocols and materials databases
Antibodypediai | 34702, 180 antibodies |
Genome annotation databases
Ensembli | ENST00000366557; ENSP00000355515; ENSG00000117009 [O15229-3] ENST00000366558; ENSP00000355516; ENSG00000117009 [O15229-2] ENST00000366559; ENSP00000355517; ENSG00000117009 [O15229-1] |
GeneIDi | 8564 |
KEGGi | hsa:8564 |
UCSCi | uc001hyy.4, human [O15229-1] |
Organism-specific databases
CTDi | 8564 |
DisGeNETi | 8564 |
EuPathDBi | HostDB:ENSG00000117009.11 |
GeneCardsi | KMO |
HGNCi | HGNC:6381, KMO |
HPAi | ENSG00000117009, Tissue enhanced (blood, liver, placenta) |
MIMi | 603538, gene |
neXtProti | NX_O15229 |
OpenTargetsi | ENSG00000117009 |
PharmGKBi | PA30172 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2614, Eukaryota |
GeneTreei | ENSGT00390000000747 |
HOGENOMi | CLU_023210_0_0_1 |
InParanoidi | O15229 |
OMAi | NLAMSNR |
OrthoDBi | 462247at2759 |
PhylomeDBi | O15229 |
TreeFami | TF312990 |
Enzyme and pathway databases
UniPathwayi | UPA00253;UER00328 |
BioCyci | MetaCyc:HS04082-MONOMER |
PathwayCommonsi | O15229 |
Reactomei | R-HSA-71240, Tryptophan catabolism |
SABIO-RKi | O15229 |
Miscellaneous databases
BioGRID-ORCSi | 8564, 6 hits in 843 CRISPR screens |
ChiTaRSi | KMO, human |
GeneWikii | KMO_(gene) |
GenomeRNAii | 8564 |
Pharosi | O15229, Tchem |
PROi | PR:O15229 |
RNActi | O15229, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000117009, Expressed in placenta and 148 other tissues |
ExpressionAtlasi | O15229, baseline and differential |
Genevisiblei | O15229, HS |
Family and domain databases
Gene3Di | 3.50.50.60, 1 hit |
HAMAPi | MF_01971, Kynurenine_monooxygenase, 1 hit |
InterProi | View protein in InterPro IPR002938, FAD-bd IPR036188, FAD/NAD-bd_sf IPR027545, Kynurenine_monooxygenase |
Pfami | View protein in Pfam PF01494, FAD_binding_3, 1 hit |
SUPFAMi | SSF51905, SSF51905, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KMO_HUMAN | |
Accessioni | O15229Primary (citable) accession number: O15229 Secondary accession number(s): A2A2U8 Q5SY09 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 4, 2006 |
Last sequence update: | February 20, 2007 | |
Last modified: | December 2, 2020 | |
This is version 166 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations