Reviewed, UniProtKB/Swiss-Prot O88867 (KMO_RAT)

Names and origin

Protein names

Recommended name:
    Kynurenine 3-monooxygenase
    EC=1.14.13.9
Alternative name(s):
    Kynurenine 3-hydroxylase

Gene names

Name:

Kmo

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	478 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 By similarity.
Catalytic activity	L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O. Ref.3
Cofactor	FAD By similarity. UniProtKB O15229
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis; pyridine-2,3-dicarboxylate from L-kynurenine: step 1/3.
Subcellular location	Mitochondrion outer membrane; Multi-pass membrane protein. Ref.3
Tissue specificity	Highest activity in liver and kidney. Low activity in spleen, stomach, intestinal tract, esophagus, heart and lung. Ref.3
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.
Sequence similarities	Belongs to the aromatic-ring hydroxylase family. KMO subfamily.
Biophysicochemical properties	Kinetic parameters: KM=11.3 µM for NADPH KM=316 µM for NADH

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Domain	Transmembrane
Ligand	FAD Flavoprotein NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	NAD metabolic process Ref.3 Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW pyridine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW tryptophan catabolic process to kynurenine Inferred from direct assay. Source: RGD
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Ref.3 Inferred from direct assay. Source: UniProtKB
Molecular function	kynurenine 3-monooxygenase activity Ref.3 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 478	478	Kynurenine 3-monooxygenase		PRO_0000229745
Regions
	Transmembrane	385 – 404	20	Potential
	Transmembrane	425 – 444	20	Potential
Amino acid modifications
	Modified residue	399	1	Phosphothreonine By similarity

Sequences

	Sequence		Length	Mass (Da)
	O88867-1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 72E775D1C05CFFAB	FASTA	478	54,353
	10 20 30 40 50 60 MASSDTEGKR VVVIGGGLVG ALNACFLAKR NFQVDVYEAR EDIRVANFMR GRSINLALSY 70 80 90 100 110 120 RGRQALKAVG LEDQIVSKGV PMKARMIHSL SGKKSAIPYG NKSQYILSIS REKLNKDLLT 130 140 150 160 170 180 AVESYPNAKV HFGHKLSKCC PEEGILTMLG PNKVPRDITC DLIVGCDGAY STVRAHLMKK 190 200 210 220 230 240 PRFDYSQQYI PHGYMELTIP PKNGEYAMEP NCLHIWPRNA FMMIALPNMD KSFTCTLFMS 250 260 270 280 290 300 FEEFEKLPTH SDVLDFFQKN FPDAIPLMGE QALMRDFFLL PAQPMISVKC SPFHLKSRCV 310 320 330 340 350 360 LMGDAAHAIV PFFGQGMNAG FEDCLVFDEL MDKFNNDLSV CLPEFSRFRI PDDHAISDLS 370 380 390 400 410 420 MYNYIEMRAH VNSRWFLFQR LLDKFLHALM PSTFIPLYTM VAFTRIRYHE AVLRWHWQKK 430 440 450 460 470 VINRGLFVLG SLVAIGSAYI LVHHLSPRPL ELLRSAWTGT SGHWNRSADI SPRVPWSH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Magagnin S., Covini N., Cini M., Bormetti R., Molinari A., Speciale C., Post C., Benatti L. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[3]	"A radiometric assay for kynurenine 3-hydroxylase based on the release of 3H2O during hydroxylation of L-[3,5-3H]kynurenine." Erickson J.B., Flanagan E.M., Russo S., Reinhard J.F. Jr. Anal. Biochem. 205:257-262(1992) [PubMed: 1332540] [Abstract] Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[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: 12402501] [Abstract] Cited for: REVIEW.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF056031 mRNA. Translation: AAC62614.1. BC088142 mRNA. Translation: AAH88142.1.
IPI	IPI00213422.
RefSeq	NP_067604.1.
UniGene	Rn.35029
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	O88867.
Proteomic databases
PRIDE	O88867.
Genome annotation databases
Ensembl	ENSRNOG00000003709. Rattus norvegicus. [Contig view]
GeneID	59113.
KEGG	rno:59113.
NMPDR	fig|10116.3.peg.9628.
Organism-specific databases
RGD	620610. Kmo.
Phylogenomic databases
HOVERGEN	O88867.
OMA	O88867. LHAIMPS.
Enzyme and pathway databases
BRENDA	1.14.13.9. 248.
Gene expression databases
ArrayExpress	O88867.
GermOnline	ENSRNOG00000003709. Rattus norvegicus.
Family and domain databases
InterPro	IPR006076. FAD-dep_OxRdtase. IPR003042. Rng_hydrolase-like. [Graphical view]
Pfam	PF01266. DAO. 1 hit. [Graphical view]
PRINTS	PR00420. RNGMNOXGNASE.
ProtoNet	Search...
Other Resources
NextBio	611759.

Entry information

Entry name

KMO_RAT

Accession

Primary (citable) accession number: O88867

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2006
Last sequence update:	November 1, 1998
Last modified:	June 16, 2009
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)