ID FMO3_MACMU Reviewed; 532 AA.
AC Q8SPQ7;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 114.
DE RecName: Full=Flavin-containing monooxygenase 3 {ECO:0000250|UniProtKB:P31513};
DE EC=1.14.13.148 {ECO:0000250|UniProtKB:P31513};
DE EC=1.14.13.32 {ECO:0000250|UniProtKB:P31513};
DE EC=1.14.13.8 {ECO:0000250|UniProtKB:P31513};
DE AltName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 3;
DE AltName: Full=Dimethylaniline oxidase 3;
DE AltName: Full=Hepatic flavin-containing monooxygenase 3;
DE Short=FMO 3;
DE AltName: Full=Trimethylamine monooxygenase;
GN Name=FMO3;
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=11717182;
RA Cashman J.R., Zhang J., Leushner J., Braun A.;
RT "Population distribution of human flavin-containing monooxygenase form 3:
RT gene polymorphisms.";
RL Drug Metab. Dispos. 29:1629-1637(2001).
CC -!- FUNCTION: Essential hepatic enzyme that catalyzes the oxygenation of a
CC wide variety of nitrogen- and sulfur-containing compounds including
CC drugs as well as dietary compounds. Plays an important role in the
CC metabolism of trimethylamine (TMA), via the production of
CC trimethylamine N-oxide (TMAO) metabolite. TMA is generated by the
CC action of gut microbiota using dietary precursors such as choline,
CC choline containing compounds, betaine or L-carnitine. By regulating
CC TMAO concentration, FMO3 directly impacts both platelet responsiveness
CC and rate of thrombus formation. {ECO:0000250|UniProtKB:P31513}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADPH + O2 + trimethylamine = H2O + NADP(+) + trimethylamine
CC N-oxide; Xref=Rhea:RHEA:31979, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15724, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:58389; EC=1.14.13.148;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31980;
CC Evidence={ECO:0000250|UniProtKB:P31513};
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:P31513};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24469;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hypotaurine + NADPH + O2 = H2O + NADP(+) + taurine;
CC Xref=Rhea:RHEA:69819, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:57853,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:507393; EC=1.14.13.8;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69820;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-nicotine + NADPH + O2 = H2O + NADP(+) + trans-(S)-nicotine
CC N(1')-oxide; Xref=Rhea:RHEA:58720, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:59806, ChEBI:CHEBI:142660;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58721;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=albendazole + H(+) + NADPH + O2 = albendazole S-oxide + H2O +
CC NADP(+); Xref=Rhea:RHEA:10796, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16664, ChEBI:CHEBI:16959,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.32;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10797;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:P32417}; Single-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P32417}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR EMBL; AY063498; AAL86612.1; -; mRNA.
DR RefSeq; NP_001028065.1; NM_001032893.1.
DR AlphaFoldDB; Q8SPQ7; -.
DR SMR; Q8SPQ7; -.
DR STRING; 9544.ENSMMUP00000010434; -.
DR PaxDb; 9544-ENSMMUP00000010434; -.
DR GeneID; 574244; -.
DR KEGG; mcc:574244; -.
DR CTD; 2328; -.
DR eggNOG; KOG1399; Eukaryota.
DR InParanoid; Q8SPQ7; -.
DR OrthoDB; 2079054at2759; -.
DR Proteomes; UP000006718; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0047638; F:albendazole monooxygenase activity; IEA:RHEA.
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:0004499; F:N,N-dimethylaniline monooxygenase activity; IBA:GO_Central.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0034899; F:trimethylamine monooxygenase activity; IEA:UniProtKB-EC.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 4.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR000960; Flavin_mOase.
DR InterPro; IPR020946; Flavin_mOase-like.
DR InterPro; IPR002255; Flavin_mOase_3.
DR PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1.
DR PANTHER; PTHR23023:SF44; DIMETHYLANILINE MONOOXYGENASE [N-OXIDE-FORMING] 3; 1.
DR Pfam; PF00743; FMO-like; 1.
DR PIRSF; PIRSF000332; FMO; 1.
DR PRINTS; PR00370; FMOXYGENASE.
DR PRINTS; PR01123; FMOXYGENASE3.
DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 2.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..532
FT /note="Flavin-containing monooxygenase 3"
FT /id="PRO_0000147655"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 9..13
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 32
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 40..41
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 60..61
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 61..62
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT BINDING 195..198
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT MOD_RES 401
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97501"
SQ SEQUENCE 532 AA; 60152 MW; 73A4D13EE2A24A72 CRC64;
MGKKVAIIGA GVSGLASIRS CLEEGLEPTC FEKSNDIGGL WKFSDHAEEG RASIYKSVFT
NSSKEMMCFP DFPYPDDFPN FMHNSKIQEY LTAFAKEKSL LKYIQFKTFV SSVNKRPDFA
TTGQWDVTTE RDGKRESAVF DAVMVCSGHH VYPNLPKESF PGLNHFKGKC FHSRDYKEPG
VFKGKRVLVV GLGNSGCDIA TELSHTAEQV VISSRSGSWV MSRVWDNGYP WDMVLITRFG
TFLKNNLPTA ISDWLYMKQM NARFKHENYG LMPLNGVLRK EPVFNDELPA CILCGIVSVK
PNVKKFTETS AIFEDGTTFE GIDCVIFATG YSYTYTFLDE SIIKNRNNEI ILFKGVFPPL
LEKSTIAVIG FVQSLGAAIP TVDLQSRWAA RVIKGTCTLP SMEDMMNDIN EKMERKHKWY
GKSETLQTDY IVYMDELSSF IGVKPNIPWL FLTDPKLAME VYFGPCSPYQ FRLVGPGKWP
GARNAILTQW DRSLKPLQTR VVGRLQKPCF FFHWLKPFAI PILLIAVFLG LT
//
