FMO5_RABIT
ID FMO5_RABIT Reviewed; 533 AA.
AC Q04799;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Flavin-containing monooxygenase 5;
DE Short=FMO 5;
DE AltName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 5 {ECO:0000305};
DE EC=1.14.13.8 {ECO:0000269|PubMed:7872795};
DE AltName: Full=Dimethylaniline oxidase 5;
DE AltName: Full=FMO 1C1;
DE AltName: Full=FMO form 3;
DE AltName: Full=Hepatic flavin-containing monooxygenase 5;
DE AltName: Full=NADPH oxidase {ECO:0000250|UniProtKB:P49326};
DE EC=1.6.3.1 {ECO:0000250|UniProtKB:P49326};
GN Name=FMO5;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8486656; DOI=10.1016/s0021-9258(18)98403-6;
RA Atta-Asafo-Adjei E., Lawton M.P., Philpot R.M.;
RT "Cloning, sequencing, distribution, and expression in Escherichia coli of
RT flavin-containing monooxygenase 1C1. Evidence for a third gene subfamily in
RT rabbits.";
RL J. Biol. Chem. 268:9681-9689(1993).
RN [2]
RP TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND FUNCTION.
RC STRAIN=Hartley; TISSUE=Liver;
RX PubMed=7872795; DOI=10.1006/abbi.1995.1163;
RA Overby L.H., Buckpitt A.R., Lawton M.P., Atta-Asafo-Adjei E., Schulze J.,
RA Philpot R.M.;
RT "Characterization of flavin-containing monooxygenase 5 (FMO5) cloned from
RT human and guinea pig: evidence that the unique catalytic properties of FMO5
RT are not confined to the rabbit ortholog.";
RL Arch. Biochem. Biophys. 317:275-284(1995).
CC -!- FUNCTION: Acts as Baeyer-Villiger monooxygenase on a broad range of
CC substrates. Catalyzes the insertion of an oxygen atom into a carbon-
CC carbon bond adjacent to a carbonyl, which converts ketones to esters
CC (By similarity). Active on diverse carbonyl compounds, whereas soft
CC nucleophiles are mostly non- or poorly reactive. In contrast with other
CC forms of FMO it is non- or poorly active on 'classical' substrates such
CC as drugs, pesticides, and dietary components containing soft
CC nucleophilic heteroatoms (PubMed:7872795). Able to oxidize drug
CC molecules bearing a carbonyl group on an aliphatic chain, such as
CC nabumetone and pentoxifylline. Also, in the absence of substrates,
CC shows slow but yet significant NADPH oxidase activity (By similarity).
CC Acts as a positive modulator of cholesterol biosynthesis as well as
CC glucose homeostasis, promoting metabolic aging via pleiotropic effects
CC (By similarity). {ECO:0000250|UniProtKB:P49326,
CC ECO:0000250|UniProtKB:P97872, ECO:0000269|PubMed:7872795}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + N,N-dimethylaniline + NADPH + O2 = H2O + N,N-
CC dimethylaniline N-oxide + NADP(+); Xref=Rhea:RHEA:24468,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16269, ChEBI:CHEBI:17735, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.14.13.8;
CC Evidence={ECO:0000269|PubMed:7872795};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24469;
CC Evidence={ECO:0000305|PubMed:7872795};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 = H2O2 + NADP(+); Xref=Rhea:RHEA:11260,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.6.3.1;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11261;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + heptan-2-one + NADPH + O2 = H2O + NADP(+) + pentyl
CC acetate; Xref=Rhea:RHEA:54836, ChEBI:CHEBI:5672, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87362;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54837;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + octan-3-one = H2O + NADP(+) + pentyl
CC propanoate; Xref=Rhea:RHEA:54840, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:80946, ChEBI:CHEBI:87373;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54841;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + octan-3-one = ethyl hexanoate + H2O +
CC NADP(+); Xref=Rhea:RHEA:54856, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:80946, ChEBI:CHEBI:86055;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54857;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexan-3-one + NADPH + O2 = ethyl butanoate + H2O +
CC NADP(+); Xref=Rhea:RHEA:54844, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:88764, ChEBI:CHEBI:89891;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54845;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexan-3-one + NADPH + O2 = H2O + NADP(+) + propyl
CC propanoate; Xref=Rhea:RHEA:54848, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:89828, ChEBI:CHEBI:89891;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54849;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + heptan-4-one + NADPH + O2 = H2O + NADP(+) + propyl
CC butanoate; Xref=Rhea:RHEA:54852, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:89484, ChEBI:CHEBI:89719;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54853;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranial + H(+) + NADPH + O2 = (1E)-2,6-dimethylhepta-
CC 1,5-dien-1-yl formate + H2O + NADP(+); Xref=Rhea:RHEA:54860,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16980, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:138375; Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54861;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + NADPH + O2 + sulcatone = 4-methylpent-3-en-1-yl acetate
CC + H2O + NADP(+); Xref=Rhea:RHEA:54864, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16310,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:138373;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54865;
CC Evidence={ECO:0000250|UniProtKB:P49326};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P49326}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P49326}.
CC -!- TISSUE SPECIFICITY: Kidney and liver. {ECO:0000269|PubMed:7872795}.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR EMBL; L08449; AAA31235.1; -; mRNA.
DR PIR; A45912; A45912.
DR PIR; A46677; A46677.
DR RefSeq; NP_001075714.1; NM_001082245.1.
DR AlphaFoldDB; Q04799; -.
DR SMR; Q04799; -.
DR STRING; 9986.ENSOCUP00000008053; -.
DR PRIDE; Q04799; -.
DR GeneID; 100009064; -.
DR KEGG; ocu:100009064; -.
DR CTD; 2330; -.
DR eggNOG; KOG1399; Eukaryota.
DR InParanoid; Q04799; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004031; F:aldehyde oxidase activity; ISS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0106294; F:NADPH oxidase H202-forming activity; IEA:RHEA.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0070995; P:NADPH oxidation; ISS:UniProtKB.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR000960; Flavin_mOase.
DR InterPro; IPR020946; Flavin_mOase-like.
DR InterPro; IPR002257; Flavin_mOase_5.
DR Pfam; PF00743; FMO-like; 1.
DR PIRSF; PIRSF000332; FMO; 1.
DR PRINTS; PR00370; FMOXYGENASE.
DR PRINTS; PR01125; FMOXYGENASE5.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Lipid metabolism; Membrane;
KW Methylation; Microsome; Monooxygenase; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..533
FT /note="Flavin-containing monooxygenase 5"
FT /id="PRO_0000147667"
FT TRANSMEM 513..533
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 10..14
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 33
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 41..42
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 62..63
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 196..199
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT MOD_RES 5
FT /note="Dimethylated arginine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4C0"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49326"
FT MOD_RES 56
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P49326"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49326"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49326"
FT MOD_RES 284
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P49326"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97872"
SQ SEQUENCE 533 AA; 59845 MW; 188617ACA56E9286 CRC64;
MAGKRVAVIG AGASGLACIK CCLEEGLEPV CFERTDDIGG LWRFQESPDE GRASIYKSVI
INTSKEMMCF SDYPIPDHFP NFMHNSQVLE YFRMYAKEFG LLKYIQFKTT VCSVKKRPDF
STSGQWEVLT ECEGKKESAV FDGVLVCTGH HTSAHLPLES FPGIEKFKGQ YLHSRDYKNP
EKFTGKRVIV IGIGNSGGDL AVEISHTAKQ VFLSTRRGAW IMNRVGDHGY PIDILLSSRF
SQFLKKITGE TIANSFLERK MNQRFDHAMF GLKPKHRALS QHPTVNDDLP NRIISGSVKI
KGNVKEFTET AAIFEDGSRE DDIDAVIFAT GYSFSFPFLE DSVKVVKNKV SLYKKVFPPN
LEKPTLAIIG LIQPLGAIMP ISELQARWAT LVFKGLKTLP SQSEMMTEIS QVQEKMAKRY
VESQRHTIQG DYIETMEEIA DLVGVRPNLL SLAFTDPRLA LQLLLGPCTP VHYRLQGRGK
WDGARKTILT VEDRIRKPLM TRVTESSNSV TSMMTMGKFM LAIAFLAIAV VYF
