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Protein

Kynurenine 3-monooxygenase

Gene

KMO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes 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.

Catalytic activityi

L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O.UniRule annotation2 Publications

Cofactori

FADUniRule annotation1 Publication

Kineticsi

  1. KM=24.1 µM for L-kynurenine2 Publications
  1. Vmax=8.5 µmol/min/mg enzyme2 Publications

pH dependencei

Optimum pH is 7.5.2 Publications

Pathway: 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.

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Pyridine nucleotide biosynthesis

Keywords - Ligandi

FAD, Flavoprotein, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS04082-MONOMER.
ReactomeiREACT_916. Tryptophan catabolism.
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
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:6381. KMO.

Subcellular locationi

  • Mitochondrion outer membrane UniRule annotation1 Publication; Multi-pass membrane protein UniRule annotation1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei385 – 40420HelicalUniRule annotationAdd
BLAST
Transmembranei425 – 44521HelicalUniRule annotationAdd
BLAST

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • mitochondrial inner membrane Source: Ensembl
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30172.

Polymorphism and mutation databases

BioMutaiKMO.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 486486Kynurenine 3-monooxygenaseCuratedPRO_0000229742Add
BLAST

Proteomic databases

MaxQBiO15229.
PaxDbiO15229.
PRIDEiO15229.

PTM databases

PhosphoSiteiO15229.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO15229.
CleanExiHS_KMO.
ExpressionAtlasiO15229. baseline and differential.
GenevisibleiO15229. HS.

Organism-specific databases

HPAiHPA031115.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000355517.

Structurei

3D structure databases

ProteinModelPortaliO15229.
SMRiO15229. Positions 9-367.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0654.
GeneTreeiENSGT00390000000747.
HOVERGENiHBG057213.
InParanoidiO15229.
KOiK00486.
OMAiQPMISVK.
OrthoDBiEOG7KSX8D.
PhylomeDBiO15229.
TreeFamiTF312990.

Family and domain databases

HAMAPiMF_01971. Kynurenine_monooxygenase.
InterProiIPR027545. Kynurenine_monooxygenase.
IPR002938. mOase_FAD-bd.
[Graphical view]
PfamiPF01494. FAD_binding_3. 1 hit.
[Graphical view]

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.Curated
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.Curated
Show »
Length:452
Mass (Da):51,682
Checksum:i59D707C5D8F21C03
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti452 – 4521R → C.2 Publications
Corresponds to variant rs1053230 [ dbSNP | Ensembl ].
VAR_030845

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei367 – 40034Missing in isoform 3. 1 PublicationVSP_051972Add
BLAST
Alternative sequencei367 – 37913Missing in isoform 2. 1 PublicationVSP_051973Add
BLAST

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.3. human. [O15229-2]
uc009xgo.2. human. [O15229-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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

3D structure databases

ProteinModelPortaliO15229.
SMRiO15229. Positions 9-367.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000355517.

Chemistry

BindingDBiO15229.
ChEMBLiCHEMBL2145.

PTM databases

PhosphoSiteiO15229.

Polymorphism and mutation databases

BioMutaiKMO.

Proteomic databases

MaxQBiO15229.
PaxDbiO15229.
PRIDEiO15229.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366557; ENSP00000355515; ENSG00000117009. [O15229-3]
ENST00000366558; ENSP00000355516; ENSG00000117009. [O15229-2]
ENST00000366559; ENSP00000355517; ENSG00000117009. [O15229-1]
GeneIDi8564.
KEGGihsa:8564.
UCSCiuc001hyy.3. human. [O15229-2]
uc009xgo.2. human. [O15229-1]

Organism-specific databases

CTDi8564.
GeneCardsiGC01P241695.
HGNCiHGNC:6381. KMO.
HPAiHPA031115.
MIMi603538. gene.
neXtProtiNX_O15229.
PharmGKBiPA30172.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0654.
GeneTreeiENSGT00390000000747.
HOVERGENiHBG057213.
InParanoidiO15229.
KOiK00486.
OMAiQPMISVK.
OrthoDBiEOG7KSX8D.
PhylomeDBiO15229.
TreeFamiTF312990.

Enzyme and pathway databases

UniPathwayiUPA00253; UER00328.
BioCyciMetaCyc:HS04082-MONOMER.
ReactomeiREACT_916. Tryptophan catabolism.

Miscellaneous databases

ChiTaRSiKMO. human.
GeneWikiiKMO_(gene).
GenomeRNAii8564.
NextBioi32109.
PROiO15229.
SOURCEiSearch...

Gene expression databases

BgeeiO15229.
CleanExiHS_KMO.
ExpressionAtlasiO15229. baseline and differential.
GenevisibleiO15229. HS.

Family and domain databases

HAMAPiMF_01971. Kynurenine_monooxygenase.
InterProiIPR027545. Kynurenine_monooxygenase.
IPR002938. mOase_FAD-bd.
[Graphical view]
PfamiPF01494. FAD_binding_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and functional expression of human kynurenine 3-monooxygenase."
    Alberati-Giani D., Cesura A.M., Broger C., Warren W.D., Rover S., Malherbe P.
    FEBS Lett. 410:407-412(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT CYS-452.
    Tissue: LiverImported.
  2. "Functional characterization and mechanism of action of recombinant human kynurenine 3-hydroxylase."
    Breton J., Avanzi N., Magagnin S., Covini N., Magistrelli G., Cozzi L., Isacchi A.
    Eur. J. Biochem. 267:1092-1099(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT CYS-452.
    Tissue: Liver1 Publication.
  3. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Endogenous kynurenines as targets for drug discovery and development."
    Stone T.W., Darlington L.G.
    Nat. Rev. Drug Discov. 1:609-620(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiKMO_HUMAN
AccessioniPrimary (citable) accession number: O15229
Secondary accession number(s): A2A2U8
, A2A2U9, A2A2V0, Q5SY07, Q5SY08, Q5SY09
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: February 20, 2007
Last modified: June 24, 2015
This is version 126 of the entry and version 2 of the sequence. [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

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

Keywords - Technical termi

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.