ID FMO5_CAVPO Reviewed; 533 AA.
AC P49109;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 24-JAN-2024, entry version 125.
DE RecName: Full=Flavin-containing monooxygenase 5;
DE Short=FMO 5 {ECO:0000305};
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=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 Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND
RP 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 a 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: Expressed in liver. {ECO:0000269|PubMed:7872795}.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L37081; AAA67848.1; -; mRNA.
DR PIR; S71617; S71617.
DR RefSeq; NP_001166418.1; NM_001172947.1.
DR RefSeq; XP_012998115.1; XM_013142661.1.
DR RefSeq; XP_012998116.1; XM_013142662.1.
DR RefSeq; XP_012998117.1; XM_013142663.1.
DR AlphaFoldDB; P49109; -.
DR SMR; P49109; -.
DR STRING; 10141.ENSCPOP00000012498; -.
DR Ensembl; ENSCPOT00000014008.3; ENSCPOP00000012497.2; ENSCPOG00000013868.4.
DR Ensembl; ENSCPOT00000014009.3; ENSCPOP00000012498.3; ENSCPOG00000013868.4.
DR GeneID; 100135521; -.
DR KEGG; cpoc:100135521; -.
DR CTD; 2330; -.
DR VEuPathDB; HostDB:ENSCPOG00000013868; -.
DR eggNOG; KOG1399; Eukaryota.
DR GeneTree; ENSGT00940000160493; -.
DR HOGENOM; CLU_006909_8_2_1; -.
DR InParanoid; P49109; -.
DR OMA; FMEWEHH; -.
DR OrthoDB; 2079054at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR Bgee; ENSCPOG00000013868; Expressed in liver and 12 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004031; F:aldehyde oxidase activity; ISS:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0047822; F:hypotaurine dehydrogenase activity; IEA:UniProtKB-EC.
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; FAD/NAD(P)-binding domain; 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 PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1.
DR PANTHER; PTHR23023:SF78; FLAVIN-CONTAINING MONOOXYGENASE 5; 1.
DR Pfam; PF00743; FMO-like; 1.
DR PIRSF; PIRSF000332; FMO; 1.
DR PRINTS; PR00370; FMOXYGENASE.
DR PRINTS; PR01125; FMOXYGENASE5.
DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 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_0000147664"
FT TRANSMEM 510..530
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; 60125 MW; E0C06EE4C6B6EFDD CRC64;
MTKKRIAVIG GGVSGLSSIK CCLEEGLEPV CFERSADIGG LWRFQENPEE GRASIYKSVI
INTSKEMMCF SDYPIPDHYP NFMHNSHVLE YFRMYAKEFG LLKYIQFKTT VCNVKKRPDF
STSGQWEVVT EHEGKTKVDV FDAVMVCTGH HTNAHLPLES FPGIEKFKGQ YFHSRDYKNP
EAFTGKRVVI IGIGNSGGDL AVEISHTAKQ VFLSTRRGSW ILNRVGKHGY PTDVLLSSRF
TYFLSKILGQ SLSNAYVEKQ MNERFDHEMF GLKPKHRAMS QHPTVNDDLP NRIIAGMVKV
KGNVKEFTET AAIFEDGSRE DDIDAVIFAT GYSFDFPFLE DSVKVVKNKV SLYKKVFPPN
LERPTLAIIG LIQPLGAIMP ISELQGRWAV QVFKGLKTLP SQSEMMAEIT KAQEEIAKRY
VDSQRHTIQG DYIQTMEEIA EFVGVKPNLL SLAFTDPKLA LKLFFGPCTP IHYRLQGPGK
WHGARKAILT TYDRIRKPLN TRETEKSNSM VSAVTTGCFM LAVVFFAIIM AYA
//
