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Protein

Kynurenine 3-monooxygenase

Gene

KMO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O.UniRule annotation3 Publications

Cofactori

FADUniRule annotation2 Publications

Kineticsi

Kcat is 0.24 sec(-1) for L-kynurenine.1 Publication
  1. KM=24.1 µM for L-kynurenine3 Publications
  2. KM=2 µM for L-kynurenine1 Publication
  3. KM=78 µM for L-kynurenine1 Publication
  1. Vmax=8.5 µmol/min/mg enzyme2 Publications

pH dependencei

Optimum pH is 7.5.2 Publications

Pathwayi: NAD(+) biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes quinolinate from L-kynurenine.UniRule annotation
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO), Kynurenine 3-monooxygenase (KMO)
  2. Kynureninase (KYNU), Kynureninase (KYNU), Kynureninase (KYNU)
  3. 3-hydroxyanthranilate 3,4-dioxygenase (HAAO)
This subpathway is part of the pathway NAD(+) biosynthesis, which is itself part of Cofactor biosynthesis.
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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei19FAD; via amide nitrogenCombined sources1 Publication1
Binding sitei57FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1
Binding sitei85L-kynurenineBy similarity1
Binding sitei99L-kynurenineBy similarity1
Binding sitei111FADCombined sources1 Publication1
Binding sitei136FAD; via amide nitrogen and carbonyl oxygenCombined sources1 Publication1
Binding sitei172FADCombined sources1 Publication1
Binding sitei304FAD; via amide nitrogenCombined sources1 Publication1
Binding sitei363L-kynurenineBy similarity1
Binding sitei398L-kynurenineBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi37 – 40FADCombined sources1 Publication4
Nucleotide bindingi317 – 318FADCombined sources1 Publication2

GO - Molecular functioni

  • FAD binding Source: UniProtKB
  • flavin adenine dinucleotide binding Source: UniProtKB
  • kynurenine 3-monooxygenase activity Source: UniProtKB
  • NAD(P)H oxidase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
Biological processPyridine nucleotide biosynthesis
LigandFAD, Flavoprotein, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS04082-MONOMER
ReactomeiR-HSA-71240 Tryptophan catabolism
SABIO-RKiO15229
UniPathwayiUPA00253; 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
Name:KMOUniRule annotationImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117009.11
HGNCiHGNC:6381 KMO
MIMi603538 gene
neXtProtiNX_O15229

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei385 – 404HelicalUniRule annotationAdd BLAST20
Transmembranei425 – 445HelicalUniRule annotationAdd BLAST21

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi85R → A or K: Abolishes kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi99Y → A: Abolishes kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi99Y → F: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi312 – 313FF → AA: Abolishes NADPH oxidase activity. 1 Publication2
Mutagenesisi312F → A: Decreases to 30% NADPH oxidase activity. 1 Publication1
Mutagenesisi313F → A: Decreases to 50% NADPH oxidase activity. 1 Publication1
Mutagenesisi363N → A: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi363N → D: Abolishes kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi366E → A or Q: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi367M → A: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi367M → L: Strongly decreases kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi398Y → A or F: Abolishes kynurenine 3-monooxygenase activity. 1 Publication1
Mutagenesisi465N → A: Not glycosylted. Reduces to 80% kynurenine 3-monooxygenase activity. 1 Publication1

Organism-specific databases

DisGeNETi8564
OpenTargetsiENSG00000117009
PharmGKBiPA30172

Chemistry databases

ChEMBLiCHEMBL2145
GuidetoPHARMACOLOGYi2886

Polymorphism and mutation databases

BioMutaiKMO

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002297421 – 486Kynurenine 3-monooxygenaseCuratedAdd BLAST486

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi465N-linked (GalNAc...) asparagine1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiO15229
PaxDbiO15229
PeptideAtlasiO15229
PRIDEiO15229
ProteomicsDBi48519
48520 [O15229-2]
48521 [O15229-3]

PTM databases

iPTMnetiO15229
PhosphoSitePlusiO15229

Expressioni

Tissue specificityi

Highest levels in placenta and liver. Detectable in kidney.1 Publication

Gene expression databases

BgeeiENSG00000117009
CleanExiHS_KMO
ExpressionAtlasiO15229 baseline and differential
GenevisibleiO15229 HS

Organism-specific databases

HPAiHPA031115
HPA056942

Interactioni

Protein-protein interaction databases

BioGridi114133, 3 interactors
STRINGi9606.ENSP00000355517

Chemistry databases

BindingDBiO15229

Structurei

Secondary structure

1486
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi10 – 14Combined sources5
Helixi18 – 28Combined sources11
Turni29 – 31Combined sources3
Beta strandi33 – 37Combined sources5
Turni43 – 45Combined sources3
Beta strandi55 – 58Combined sources4
Helixi60 – 68Combined sources9
Helixi72 – 76Combined sources5
Beta strandi80 – 82Combined sources3
Beta strandi84 – 88Combined sources5
Beta strandi94 – 98Combined sources5
Helixi102 – 104Combined sources3
Beta strandi106 – 110Combined sources5
Helixi111 – 123Combined sources13
Beta strandi128 – 131Combined sources4
Beta strandi138 – 140Combined sources3
Turni141 – 144Combined sources4
Beta strandi145 – 148Combined sources4
Beta strandi156 – 159Combined sources4
Beta strandi161 – 165Combined sources5
Helixi172 – 177Combined sources6
Beta strandi189 – 199Combined sources11
Beta strandi202 – 205Combined sources4
Beta strandi212 – 217Combined sources6
Beta strandi222 – 227Combined sources6
Beta strandi233 – 240Combined sources8
Helixi241 – 244Combined sources4
Helixi250 – 260Combined sources11
Helixi264 – 268Combined sources5
Helixi270 – 277Combined sources8
Beta strandi283 – 286Combined sources4
Beta strandi288 – 290Combined sources3
Beta strandi293 – 295Combined sources3
Turni296 – 298Combined sources3
Beta strandi299 – 301Combined sources3
Helixi303 – 305Combined sources3
Turni311 – 313Combined sources3
Helixi316 – 333Combined sources18
Turni334 – 336Combined sources3
Helixi338 – 349Combined sources12
Beta strandi363 – 365Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5X68X-ray2.10A/B1-374[»]
ProteinModelPortaliO15229
SMRiO15229
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

Transmembrane domains are required for enzymatic activity.2 Publications

Sequence similaritiesi

Belongs to the aromatic-ring hydroxylase family. KMO subfamily.UniRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2614 Eukaryota
COG0654 LUCA
GeneTreeiENSGT00390000000747
HOVERGENiHBG057213
InParanoidiO15229
KOiK00486
OMAiMPSTFIP
OrthoDBiEOG091G0769
PhylomeDBiO15229
TreeFamiTF312990

Family and domain databases

Gene3Di3.50.50.60, 1 hit
HAMAPiMF_01971 Kynurenine_monooxygenase, 1 hit
InterProiView protein in InterPro
IPR002938 FAD-bd
IPR036188 FAD/NAD-bd_sf
IPR027545 Kynurenine_monooxygenase
PfamiView protein in Pfam
PF01494 FAD_binding_3, 1 hit
SUPFAMiSSF51905 SSF51905, 2 hits

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 12 Publications (identifier: O15229-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:486
Mass (Da):55,810
Last modified:February 20, 2007 - v2
Checksum:i164870D52E62A08A
GO
Isoform 21 Publication (identifier: O15229-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     367-379: Missing.

Note: Gene model based on cDNA data. No experimental confirmation available.
Show »
Length:473
Mass (Da):54,205
Checksum:i9D898B2A91A76782
GO
Isoform 31 Publication (identifier: O15229-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     367-400: Missing.

Note: Gene model based on mouse cDNA data. No experimental confirmation available.
Show »
Length:452
Mass (Da):51,682
Checksum:i59D707C5D8F21C03
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030845452R → C2 PublicationsCorresponds to variant dbSNP:rs1053230Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_051972367 – 400Missing in isoform 3. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_051973367 – 379Missing in isoform 2. 1 PublicationAdd BLAST13

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.
CCDSiCCDS1618.1 [O15229-1]
RefSeqiNP_003670.2, NM_003679.4 [O15229-1]
UniGeneiHs.731056
Hs.744065

Genome annotation databases

EnsembliENST00000366557; ENSP00000355515; ENSG00000117009 [O15229-3]
ENST00000366558; ENSP00000355516; ENSG00000117009 [O15229-2]
ENST00000366559; ENSP00000355517; ENSG00000117009 [O15229-1]
GeneIDi8564
KEGGihsa:8564
UCSCiuc001hyy.4 human [O15229-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKMO_HUMAN
AccessioniPrimary (citable) accession number: O15229
Secondary accession number(s): A2A2U8
, A2A2U9, A2A2V0, Q5SY07, Q5SY08, Q5SY09
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: February 20, 2007
Last modified: June 20, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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