ID   KMO_AEDAE               Reviewed;         476 AA.
AC   Q86PM2; Q16XF6; Q86PM3; Q8WSB2;
DT   10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2009, sequence version 2.
DT   02-SEP-2026, entry version 117.
DE   RecName: Full=Kynurenine 3-monooxygenase {ECO:0000255|HAMAP-Rule:MF_03018};
DE            EC=1.14.13.9 {ECO:0000255|HAMAP-Rule:MF_03018};
DE   AltName: Full=Kynurenine 3-hydroxylase {ECO:0000255|HAMAP-Rule:MF_03018};
GN   Name=kh; ORFNames=AAEL008879;
OS   Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida;
OC   Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota;
OC   Aparaglossata; Panorpida; Diptera; Nematocera; Culicoidea; Culicidae;
OC   Culicinae; Aedini; Aedes; Stegomyia.
OX   NCBI_TaxID=7159;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   STRAIN=Liverpool;
RA   Fang J., Li J.;
RT   "Isolation and characterization of kynurenine monooxygenase gene of Aedes
RT   aegypti.";
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP   ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=Rockefeller;
RX   PubMed=12974953; DOI=10.1046/j.1365-2583.2003.00433.x;
RA   Han Q., Calvo E., Marinotti O., Fang J., Rizzi M., James A.A., Li J.;
RT   "Analysis of the wild-type and mutant genes encoding the enzyme kynurenine
RT   monooxygenase of the yellow fever mosquito, Aedes aegypti.";
RL   Insect Mol. Biol. 12:483-490(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=LVPib12;
RX   PubMed=17510324; DOI=10.1126/science.1138878;
RA   Nene V., Wortman J.R., Lawson D., Haas B.J., Kodira C.D., Tu Z.J.,
RA   Loftus B.J., Xi Z., Megy K., Grabherr M., Ren Q., Zdobnov E.M., Lobo N.F.,
RA   Campbell K.S., Brown S.E., Bonaldo M.F., Zhu J., Sinkins S.P.,
RA   Hogenkamp D.G., Amedeo P., Arensburger P., Atkinson P.W., Bidwell S.L.,
RA   Biedler J., Birney E., Bruggner R.V., Costas J., Coy M.R., Crabtree J.,
RA   Crawford M., DeBruyn B., DeCaprio D., Eiglmeier K., Eisenstadt E.,
RA   El-Dorry H., Gelbart W.M., Gomes S.L., Hammond M., Hannick L.I.,
RA   Hogan J.R., Holmes M.H., Jaffe D., Johnston S.J., Kennedy R.C., Koo H.,
RA   Kravitz S., Kriventseva E.V., Kulp D., Labutti K., Lee E., Li S.,
RA   Lovin D.D., Mao C., Mauceli E., Menck C.F., Miller J.R., Montgomery P.,
RA   Mori A., Nascimento A.L., Naveira H.F., Nusbaum C., O'Leary S.B., Orvis J.,
RA   Pertea M., Quesneville H., Reidenbach K.R., Rogers Y.-H.C., Roth C.W.,
RA   Schneider J.R., Schatz M., Shumway M., Stanke M., Stinson E.O.,
RA   Tubio J.M.C., Vanzee J.P., Verjovski-Almeida S., Werner D., White O.R.,
RA   Wyder S., Zeng Q., Zhao Q., Zhao Y., Hill C.A., Raikhel A.S., Soares M.B.,
RA   Knudson D.L., Lee N.H., Galagan J., Salzberg S.L., Paulsen I.T.,
RA   Dimopoulos G., Collins F.H., Bruce B., Fraser-Liggett C.M., Severson D.W.;
RT   "Genome sequence of Aedes aegypti, a major arbovirus vector.";
RL   Science 316:1718-1723(2007).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=9569641; DOI=10.1016/s0965-1748(97)00084-2;
RA   Cornel A.J., Benedict M.Q., Rafferty C.S., Howells A.J., Collins F.H.;
RT   "Transient expression of the Drosophila melanogaster cinnabar gene rescues
RT   eye color in the white eye (WE) strain of Aedes aegypti.";
RL   Insect Biochem. Mol. Biol. 27:993-997(1997).
CC   -!- FUNCTION: Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form
CC       3-hydroxy-L-kynurenine (L-3OHKyn) (By similarity) (PubMed:12974953). 3-
CC       hydroxy-L-kynurenine is an essential precursor for the ommochrome
CC       pigment biosynthesis pathway involved in eye color (PubMed:9569641).
CC       Probably not involved in the synthesis of quinolinic acid (By
CC       similarity). {ECO:0000250|UniProtKB:A1Z746, ECO:0000255|HAMAP-
CC       Rule:MF_03018, ECO:0000269|PubMed:12974953,
CC       ECO:0000269|PubMed:9569641}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-kynurenine + NADPH + O2 + H(+) = 3-hydroxy-L-kynurenine +
CC         NADP(+) + H2O; Xref=Rhea:RHEA:20545, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:57959, ChEBI:CHEBI:58125, ChEBI:CHEBI:58349;
CC         EC=1.14.13.9; Evidence={ECO:0000255|HAMAP-Rule:MF_03018,
CC         ECO:0000269|PubMed:12974953};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03018};
CC   -!- ACTIVITY REGULATION: Inhibited by pyridoxal phosphate and chloride
CC       ions. {ECO:0000269|PubMed:12974953}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.89 mM for L-kynurenine {ECO:0000269|PubMed:12974953};
CC         KM=0.82 mM for NADPH {ECO:0000269|PubMed:12974953};
CC         Vmax=3550 nmol/min/mg enzyme toward L-kynurenine
CC         {ECO:0000269|PubMed:12974953};
CC         Vmax=3821 nmol/min/mg enzyme toward NADPH
CC         {ECO:0000269|PubMed:12974953};
CC       pH dependence:
CC         Optimum pH is between 7.0 and 7.5. {ECO:0000269|PubMed:12974953};
CC       Temperature dependence:
CC         Optimum temperature is 40 degrees Celsius.
CC         {ECO:0000269|PubMed:12974953};
CC   -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from
CC       L-kynurenine: step 1/3. {ECO:0000255|HAMAP-Rule:MF_03018}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03018}.
CC       Membrane {ECO:0000255|HAMAP-Rule:MF_03018}; Multi-pass membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_03018}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q86PM2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q86PM2-2; Sequence=VSP_036237;
CC   -!- DISRUPTION PHENOTYPE: White eyes due to lack of ommochrome pigment
CC       production. {ECO:0000269|PubMed:9569641}.
CC   -!- MISCELLANEOUS: Mosquitoes and other insects appear to lack the ability
CC       to produce quinolinate and NAD(+) from tryptophan. They lack orthologs
CC       of mammalian 3-hydroxyanthranilate 3,4-dioxygenase (HAAO), which
CC       catalyzes the downstream conversion of 3-hydroxyanthranilate to
CC       quinolinate, and Nicotinate-nucleotide pyrophosphorylase (QPRT), which
CC       catalyzes the downstream conversion of quinolinate to nicotinate beta-
CC       D-ribonucleotide (Probable). This enzyme is thus not involved in the
CC       quinolinate and NAD(+) biosynthesis pathway (Probable). {ECO:0000305,
CC       ECO:0000305|PubMed:12974953}.
CC   -!- SIMILARITY: Belongs to the aromatic-ring hydroxylase family. KMO
CC       subfamily. {ECO:0000255|HAMAP-Rule:MF_03018}.
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DR   EMBL; AF325508; AAL37368.1; -; mRNA.
DR   EMBL; AY194224; AAO27575.1; -; mRNA.
DR   EMBL; AY194225; AAO27576.1; -; mRNA.
DR   EMBL; CH477539; EAT39312.1; -; Genomic_DNA.
DR   EMBL; CH477539; EAT39313.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q86PM2; -.
DR   SMR; Q86PM2; -.
DR   FunCoup; Q86PM2; 201.
DR   STRING; 7159.Q86PM2; -.
DR   PaxDb; 7159-Q86PM2; -.
DR   GeneID; 5571188; -.
DR   KEGG; aag:5571188; -.
DR   CTD; 35724; -.
DR   VEuPathDB; VectorBase:AAEL008879; -.
DR   eggNOG; KOG2614; Eukaryota.
DR   HOGENOM; CLU_023210_0_1_1; -.
DR   InParanoid; Q86PM2; -.
DR   OMA; REFMFIA; -.
DR   OrthoDB; 10053569at2759; -.
DR   PhylomeDB; Q86PM2; -.
DR   BRENDA; 1.14.13.9; 149.
DR   UniPathway; UPA00253; UER00328.
DR   Proteomes; UP000008820; Unassembled WGS sequence.
DR   GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0004502; F:kynurenine 3-monooxygenase activity; IDA:UniProtKB.
DR   GO; GO:0034354; P:'de novo' NAD+ biosynthetic process from L-tryptophan; IEA:UniProtKB-UniRule.
DR   GO; GO:0006569; P:L-tryptophan catabolic process; IEA:UniProtKB-UniRule.
DR   GO; GO:0019674; P:NAD+ metabolic process; IDA:UniProtKB.
DR   GO; GO:0019805; P:quinolinate biosynthetic process; IEA:UniProtKB-UniRule.
DR   FunFam; 3.50.50.60:FF:000129; Kynurenine 3-monooxygenase; 1.
DR   Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1.
DR   HAMAP; MF_01971; Kynurenine_monooxygenase; 1.
DR   InterPro; IPR002938; FAD-bd.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR027545; Kynurenine_monooxygenase.
DR   PANTHER; PTHR46028; KYNURENINE 3-MONOOXYGENASE; 1.
DR   PANTHER; PTHR46028:SF2; KYNURENINE 3-MONOOXYGENASE; 1.
DR   Pfam; PF01494; FAD_binding_3; 1.
DR   PRINTS; PR00420; RNGMNOXGNASE.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; FAD; Flavoprotein; Membrane; Mitochondrion;
KW   Monooxygenase; NADP; Oxidoreductase; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..476
FT                   /note="Kynurenine 3-monooxygenase"
FT                   /id="PRO_0000361912"
FT   TRANSMEM        397..420
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03018"
FT   TRANSMEM        433..455
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03018"
FT   BINDING         28
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O15229"
FT   BINDING         46..49
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O15229"
FT   BINDING         66
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O15229"
FT   BINDING         94
FT                   /ligand="L-kynurenine"
FT                   /ligand_id="ChEBI:CHEBI:57959"
FT                   /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT   BINDING         108
FT                   /ligand="L-kynurenine"
FT                   /ligand_id="ChEBI:CHEBI:57959"
FT                   /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT   BINDING         121
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O15229"
FT   BINDING         146
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O15229"
FT   BINDING         316
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O15229"
FT   BINDING         329..330
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O15229"
FT   BINDING         375
FT                   /ligand="L-kynurenine"
FT                   /ligand_id="ChEBI:CHEBI:57959"
FT                   /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT   BINDING         410
FT                   /ligand="L-kynurenine"
FT                   /ligand_id="ChEBI:CHEBI:57959"
FT                   /evidence="ECO:0000250|UniProtKB:Q84HF5"
FT   VAR_SEQ         379..432
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12974953"
FT                   /id="VSP_036237"
FT   CONFLICT        13
FT                   /note="L -> S (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        113
FT                   /note="N -> H (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        169
FT                   /note="T -> A (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        260
FT                   /note="K -> Q (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        286
FT                   /note="V -> F (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        312
FT                   /note="V -> A (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        345
FT                   /note="Q -> E (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        407
FT                   /note="V -> F (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        441
FT                   /note="C -> S (in Ref. 1; AAL37368)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   476 AA;  54232 MW;  DC41758284BC6C6F CRC64;
     MTAQYKQTNT NGLTARNLNV AVVGGGLVGS LFALHLGKKG HTVDLYEYRE DIRTAELVIG
     RSINLALSAR GRKALAEVGL EDALLQHGIP MKGRMLHDLK GNRKIVPYDA NTNQCIYSVG
     RKHLNEVLLD AAEKYPNIHL YFNKKLQSAN LDEGEMSFID PTTKESTHTK ADLIVGCDGA
     YSAVRKEIVK RPGYDYSQTY IEHGYLELCI PPTKDGDFAM PHNYLHIWPR GKFMMIALPN
     QDRTWTVTLF MPFTNFNSIK CDGDLLKFFR TYFPDAIDLI GRERLVKDFF KTRPQSLVMI
     KCKPYNVGGK AVIIGDAAHA MVPFYGQGMN AGFEDCTVLT ELFNQHGSDV DRILAEFSDT
     RWEDAHSICD LAMYNYVEMR DLVTKRSYLF RKKLDELLYW MLPNTWVPLY NSVSFSHMRY
     SKCIANRKWQ DKILTRVLYC CSITAVAAAG YFGYKYGNMD LVQHYSSSVL QLLKLK
//