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O15229 (KMO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kynurenine 3-monooxygenase

EC=1.14.13.9
Alternative name(s):
Kynurenine 3-hydroxylase
Gene names
Name:KMO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length486 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O. Ref.1

Cofactor

FAD. Ref.2

Pathway

Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from L-kynurenine: step 1/3.

Subcellular location

Mitochondrion outer membrane; Multi-pass membrane protein Ref.1.

Tissue specificity

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

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. Ref.1

Sequence similarities

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

Biophysicochemical properties

Kinetic parameters:

KM=24.1 µM for L-kynurenine Ref.1

Vmax=8.5 µmol/min/mg enzyme Ref.2

pH dependence:

Optimum pH is 7.5. Ref.2

Ontologies

Keywords
   Biological processPyridine nucleotide biosynthesis
   Cellular componentMembrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandFAD
Flavoprotein
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_process'de novo' NAD biosynthetic process from tryptophan

Inferred from electronic annotation. Source: UniProtKB-HAMAP

anthranilate metabolic process

Inferred from electronic annotation. Source: UniProtKB-HAMAP

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

kynurenine metabolic process

Inferred from direct assay Ref.2. Source: UniProtKB

quinolinate biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-HAMAP

response to salt stress

Inferred from direct assay Ref.2. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

tryptophan catabolic process

Traceable author statement. Source: Reactome

tryptophan catabolic process to kynurenine

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial outer membrane

Inferred from sequence or structural similarity Ref.2. Source: UniProtKB

   Molecular_functionNAD(P)H oxidase activity

Inferred from direct assay Ref.2. Source: UniProtKB

flavin adenine dinucleotide binding

Inferred from direct assay Ref.2. Source: UniProtKB

kynurenine 3-monooxygenase activity

Inferred from direct assay Ref.2Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 Ref.2 (identifier: O15229-1)

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.
Isoform 2 Ref.3 (identifier: O15229-2)

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.
Isoform 3 Ref.3 (identifier: O15229-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 486486Kynurenine 3-monooxygenase
PRO_0000229742

Regions

Transmembrane385 – 40420Helical; Potential
Transmembrane425 – 44521Helical; Potential

Natural variations

Alternative sequence367 – 40034Missing in isoform 3. Ref.3
VSP_051972
Alternative sequence367 – 37913Missing in isoform 2. Ref.3
VSP_051973
Natural variant4521R → C.
Corresponds to variant rs1053230 [ dbSNP | Ensembl ].
VAR_030845

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 20, 2007. Version 2.
Checksum: 164870D52E62A08A

FASTA48655,810
        10         20         30         40         50         60 
MDSSVIQRKK VAVIGGGLVG SLQACFLAKR NFQIDVYEAR EDTRVATFTR GRSINLALSH 

        70         80         90        100        110        120 
RGRQALKAVG LEDQIVSQGI PMRARMIHSL SGKKSAIPYG TKSQYILSVS RENLNKDLLT 

       130        140        150        160        170        180 
AAEKYPNVKM HFNHRLLKCN PEEGMITVLG SDKVPKDVTC DLIVGCDGAY STVRSHLMKK 

       190        200        210        220        230        240 
PRFDYSQQYI PHGYMELTIP PKNGDYAMEP NYLHIWPRNT FMMIALPNMN KSFTCTLFMP 

       250        260        270        280        290        300 
FEEFEKLLTS NDVVDFFQKY FPDAIPLIGE KLLVQDFFLL PAQPMISVKC SSFHFKSHCV 

       310        320        330        340        350        360 
LLGDAAHAIV PFFGQGMNAG FEDCLVFDEL MDKFSNDLSL CLPVFSRLRI PDDHAISDLS 

       370        380        390        400        410        420 
MYNYIEMRAH VNSSWFIFQK NMERFLHAIM PSTFIPLYTM VTFSRIRYHE AVQRWHWQKK 

       430        440        450        460        470        480 
VINKGLFFLG SLIAISSTYL LIHYMSPRSF LRLRRPWNWI AHFRNTTCFP AKAVDSLEQI 


SNLISR 

« Hide

Isoform 2 [UniParc].

Checksum: 9D898B2A91A76782
Show »

FASTA47354,205
Isoform 3 [UniParc].

Checksum: 59D707C5D8F21C03
Show »

FASTA45251,682

References

« Hide 'large scale' references
[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: Liver.
[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: Liver.
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y13153 mRNA. Translation: CAA73613.1.
AF056032 mRNA. Translation: AAC62615.1.
AL133390 Genomic DNA. No translation available.
FO393423 Genomic DNA. No translation available.
CCDSCCDS1618.1. [O15229-1]
RefSeqNP_003670.2. NM_003679.4. [O15229-1]
UniGeneHs.731056.
Hs.744065.

3D structure databases

ProteinModelPortalO15229.
SMRO15229. Positions 9-367.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000355517.

Chemistry

BindingDBO15229.
ChEMBLCHEMBL2145.

PTM databases

PhosphoSiteO15229.

Proteomic databases

MaxQBO15229.
PaxDbO15229.
PRIDEO15229.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366557; ENSP00000355515; ENSG00000117009. [O15229-3]
ENST00000366558; ENSP00000355516; ENSG00000117009. [O15229-2]
ENST00000366559; ENSP00000355517; ENSG00000117009. [O15229-1]
GeneID8564.
KEGGhsa:8564.
UCSCuc001hyy.3. human. [O15229-2]
uc009xgo.2. human. [O15229-1]

Organism-specific databases

CTD8564.
GeneCardsGC01P241695.
HGNCHGNC:6381. KMO.
HPAHPA031115.
MIM603538. gene.
neXtProtNX_O15229.
PharmGKBPA30172.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0654.
HOVERGENHBG057213.
InParanoidO15229.
KOK00486.
OMAQPMISVK.
OrthoDBEOG7KSX8D.
PhylomeDBO15229.
TreeFamTF312990.

Enzyme and pathway databases

BioCycMetaCyc:HS04082-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00253; UER00328.

Gene expression databases

ArrayExpressO15229.
BgeeO15229.
CleanExHS_KMO.
GenevestigatorO15229.

Family and domain databases

HAMAPMF_01971. Kynurenine_monooxygenase.
InterProIPR027545. Kynurenine_monooxygenase.
IPR002938. mOase_FAD-bd.
IPR003042. Rng_hydrolase-like.
[Graphical view]
PfamPF01494. FAD_binding_3. 1 hit.
[Graphical view]
PRINTSPR00420. RNGMNOXGNASE.
ProtoNetSearch...

Other

GeneWikiKMO_(gene).
GenomeRNAi8564.
NextBio32109.
PROO15229.
SOURCESearch...

Entry information

Entry nameKMO_HUMAN
AccessionPrimary (citable) accession number: O15229
Secondary accession number(s): A2A2U8 expand/collapse secondary AC list , A2A2U9, A2A2V0, Q5SY07, Q5SY08, Q5SY09
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: February 20, 2007
Last modified: July 9, 2014
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM