FMO5_RAT
ID FMO5_RAT Reviewed; 533 AA.
AC Q8K4C0; Q6IRL0;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 129.
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:0000250|UniProtKB:P49326};
DE AltName: Full=Dimethylaniline oxidase 5;
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 {ECO:0000312|RGD:628602};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Lattard V., Benoit E.;
RT "Cloning, sequencing of flavin-containing monooxygenase 5 (FMO5) in the
RT rat.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP METHYLATION AT ARG-5, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15047867; DOI=10.1091/mbc.e04-02-0101;
RA Wu C.C., MacCoss M.J., Mardones G., Finnigan C., Mogelsvang S.,
RA Yates J.R. III, Howell K.E.;
RT "Organellar proteomics reveals Golgi arginine dimethylation.";
RL Mol. Biol. Cell 15:2907-2919(2004).
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 Active on diverse carbonyl compounds, whereas soft nucleophiles are
CC mostly non- or poorly reactive. In contrast with other forms of FMO it
CC is non- or poorly active on 'classical' substrates such as drugs,
CC pesticides, and dietary components containing soft nucleophilic
CC heteroatoms. Able to oxidize drug molecules bearing a carbonyl group on
CC an aliphatic chain, such as nabumetone and pentoxifylline. Also, in the
CC absence of substrates, shows slow but yet significant NADPH oxidase
CC activity (By similarity). Acts as a positive modulator of cholesterol
CC biosynthesis as well as glucose homeostasis, promoting metabolic aging
CC via pleiotropic effects (By similarity). {ECO:0000250|UniProtKB:P49326,
CC ECO:0000250|UniProtKB:P97872}.
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:0000250|UniProtKB:P49326};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24469;
CC Evidence={ECO:0000250|UniProtKB:P49326};
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 -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR EMBL; AF458413; AAM46761.1; -; mRNA.
DR EMBL; BC070883; AAH70883.1; -; mRNA.
DR RefSeq; NP_653340.1; NM_144739.1.
DR AlphaFoldDB; Q8K4C0; -.
DR SMR; Q8K4C0; -.
DR IntAct; Q8K4C0; 1.
DR STRING; 10116.ENSRNOP00000024423; -.
DR iPTMnet; Q8K4C0; -.
DR PhosphoSitePlus; Q8K4C0; -.
DR PaxDb; Q8K4C0; -.
DR PRIDE; Q8K4C0; -.
DR GeneID; 246248; -.
DR KEGG; rno:246248; -.
DR UCSC; RGD:628602; rat.
DR CTD; 2330; -.
DR RGD; 628602; Fmo5.
DR eggNOG; KOG1399; Eukaryota.
DR InParanoid; Q8K4C0; -.
DR OrthoDB; 405736at2759; -.
DR PhylomeDB; Q8K4C0; -.
DR TreeFam; TF105285; -.
DR SABIO-RK; Q8K4C0; -.
DR PRO; PR:Q8K4C0; -.
DR Proteomes; UP000002494; 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; ISO:RGD.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IDA:RGD.
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_0000147668"
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:0000269|PubMed:15047867"
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 284
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P49326"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97872"
FT CONFLICT 34
FT /note="R -> M (in Ref. 2; AAH70883)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="K -> E (in Ref. 2; AAH70883)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="Q -> E (in Ref. 2; AAH70883)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="R -> H (in Ref. 2; AAH70883)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 60056 MW; A16A10779E91A8F8 CRC64;
MAKKRIAVIG SGASGLTCIK CCLEEGLEPV CFERSDDIGG LWRYQENPEK GRASIYKSVI
INTSKEMMCF SDYPIPDHYP NFMHNSQVLE YFRMYAKEFG LLKYIQFKTT VCSVKKQPDF
STSGQWQVVT EHEGKQQVDV FDGVLVCTGH HTDPHLPLDS FPGIEKFKGK YFHSREYKNP
VEFTGKRVIV IGIGNSGGDL AVEISHTAKQ VFLSTRRGAW ILNRVGKRGY PIDILLSSRI
TNYLSKICGS ALKNRYMEKQ LNQRFDHEMF GLKPKHSALG QHPTINDDLP NRIISGLVKV
KGNVKEFTET AAIFEDGSRE DDIDVVIFAT GYSFAFPFLE DSVKVVQNKV SLYKKVFPPN
LEKPTLAIIG LIQPLGAIMP ISELQGRWAT QVFKGLKKLP SQSEMMAEIN KTREEMAKRY
VDSQRHTIQG DYIDTMEEIA DLVGVRPNLL SLAFTDPKLA FQLLVGPCTP VQYRLQGPGK
WAGARKTILT TEDRIRKPLM TRVVERDSSG TSLVTVRVLM LAVTFLAVIL AYF
