O15229 (KMO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	486 AA.
Sequence status	Complete.
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.
Catalytic activity	L-kynurenine + NADPH + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O. Ref.1 Ref.2
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 Ref.2 Vmax=8.5 µmol/min/mg enzyme Ref.2 pH dependence: Optimum pH is 7.5. Ref.2

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	FAD Flavoprotein NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	pyridine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW response to salt stress Inferred from direct assay Ref.2. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from sequence or structural similarity Ref.2. Source: UniProtKB
Molecular function	NAD(P)H oxidase activity Inferred from direct assay Ref.2. Source: UniProtKB electron carrier activity Inferred from direct assay Ref.1. 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 486	486	Kynurenine 3-monooxygenase		PRO_0000229742
Regions
	Transmembrane	385 – 404	20	Helical; Potential
	Transmembrane	425 – 445	21	Helical; Potential
Amino acid modifications
	Modified residue	399	1	Phosphothreonine By similarity UniProtKB Q91WN4
Natural variations
	Alternative sequence	367 – 400	34	Missing in isoform 3. Ref.3		VSP_051972
	Alternative sequence	367 – 379	13	Missing in isoform 2. Ref.3		VSP_051973
	Natural variant	452	1	R → C. Ref.1 Ref.2 Corresponds to variant rs1053230 [ dbSNP | Ensembl ].		VAR_030845

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: 164870D52E62A08A	FASTA	486	55,810
	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
	Isoform 2 [UniParc]. Checksum: 9D898B2A91A76782	FASTA	473	54,205
	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 MYNYIEKNME RFLHAIMPST FIPLYTMVTF SRIRYHEAVQ RWHWQKKVIN KGLFFLGSLI 430 440 450 460 470 AISSTYLLIH YMSPRSFLRL RRPWNWIAHF RNTTCFPAKA VDSLEQISNL ISR
	Isoform 3 [UniParc]. Checksum: 59D707C5D8F21C03	FASTA	452	51,682
	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 MYNYIEVTFS RIRYHEAVQR WHWQKKVINK GLFFLGSLIA ISSTYLLIHY MSPRSFLRLR 430 440 450 RPWNWIAHFR NTTCFPAKAV DSLEQISNLI SR

References

	« Hide 'large scale' referencesShow '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: 9237672] [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: 10672018] [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. , 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: 16710414] [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: 12402501] [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, AL591898 Genomic DNA. Translation: CAM28226.1. AL133390, AL591898 Genomic DNA. Translation: CAM28227.1. AL133390, AL591898 Genomic DNA. Translation: CAM28228.1. AL591898, AL133390 Genomic DNA. Translation: CAI13905.1. AL591898, AL133390 Genomic DNA. Translation: CAI13906.1. AL591898, AL133390 Genomic DNA. Translation: CAI13907.1.
IPI	IPI00515018. IPI00642771. IPI00645486.
RefSeq	NP_003670.2. NM_003679.4.
UniGene	Hs.728204.
3D structure databases
ProteinModelPortal	O15229.
SMR	O15229. Positions 6-369.
ModBase	Search...
Protein-protein interaction databases
STRING	O15229.
PTM databases
PhosphoSite	O15229.
Proteomic databases
PRIDE	O15229.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366559; ENSP00000355517; ENSG00000117009.
GeneID	8564.
KEGG	hsa:8564.
NMPDR	fig|9606.3.peg.3320.
UCSC	uc009xgo.1. human.
Organism-specific databases
CTD	8564.
GeneCards	GC01P241695.
H-InvDB	HIX0001738.
HGNC	HGNC:6381. KMO.
HPA	HPA031115.
MIM	603538. gene.
neXtProt	NX_O15229.
PharmGKB	PA30172.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG07321.
GeneTree	ENSGT00390000000747.
HOVERGEN	HBG057213.
InParanoid	O15229.
OMA	YFPDAIP.
OrthoDB	EOG4WH8KP.
PhylomeDB	O15229.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-15004.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	O15229.
Bgee	O15229.
CleanEx	HS_KMO.
Genevestigator	O15229.
GermOnline	ENSG00000117009. Homo sapiens.
Family and domain databases
InterPro	IPR002938. mOase_FAD-bd. IPR003042. Rng_hydrolase-like. [Graphical view]
KO	K00486.
Pfam	PF01494. FAD_binding_3. 1 hit. [Graphical view]
PRINTS	PR00420. RNGMNOXGNASE.
ProtoNet	Search...
Other
NextBio	32109.
SOURCE	Search...

Entry information

Entry name

KMO_HUMAN

Accession

Primary (citable) accession number: O15229
Secondary accession number(s): A2A2U8 , A2A2U9, A2A2V0, Q5SY07, Q5SY08, Q5SY09

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 4, 2006
Last sequence update:	February 20, 2007
Last modified:	January 25, 2012
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.