FMO3_PANTR
ID FMO3_PANTR Reviewed; 532 AA.
AC Q7YS44;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 3;
DE EC=1.14.13.8 {ECO:0000250|UniProtKB:P31513};
DE EC=1.14.14.73 {ECO:0000250|UniProtKB:P31513};
DE AltName: Full=Dimethylaniline oxidase 3;
DE AltName: Full=Hepatic flavin-containing monooxygenase 3;
DE Short=FMO 3;
DE AltName: Full=Trimethylamine monooxygenase;
DE EC=1.14.13.148;
GN Name=FMO3;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 ECO:0000250|UniProtKB:P97501}.
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 -!- 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 -!- CATALYTIC ACTIVITY:
CC Reaction=fenbendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC fenbendazole S-oxide + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:55928, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:35812, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:77092; EC=1.14.14.73;
CC Evidence={ECO:0000250|UniProtKB:P31513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=albendazole + O2 + reduced [NADPH--hemoprotein reductase] =
CC albendazole S-oxide + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:55924, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16664, ChEBI:CHEBI:16959, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.73;
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 -!- 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 -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR EMBL; AY082442; AAP57529.1; -; Genomic_DNA.
DR EMBL; AY063499; AAP57529.1; JOINED; Genomic_DNA.
DR EMBL; AY082436; AAP57529.1; JOINED; Genomic_DNA.
DR EMBL; AY082437; AAP57529.1; JOINED; Genomic_DNA.
DR EMBL; AY082438; AAP57529.1; JOINED; Genomic_DNA.
DR EMBL; AY082439; AAP57529.1; JOINED; Genomic_DNA.
DR EMBL; AY082440; AAP57529.1; JOINED; Genomic_DNA.
DR EMBL; AY082441; AAP57529.1; JOINED; Genomic_DNA.
DR RefSeq; NP_001009092.1; NM_001009092.1.
DR RefSeq; XP_009435956.2; XM_009437681.2.
DR RefSeq; XP_016818222.1; XM_016962733.1.
DR AlphaFoldDB; Q7YS44; -.
DR SMR; Q7YS44; -.
DR STRING; 9598.ENSPTRP00000002778; -.
DR PaxDb; Q7YS44; -.
DR Ensembl; ENSPTRT00000003026; ENSPTRP00000002778; ENSPTRG00000001670.
DR GeneID; 457505; -.
DR KEGG; ptr:457505; -.
DR CTD; 2328; -.
DR VGNC; VGNC:544; FMO3.
DR eggNOG; KOG1399; Eukaryota.
DR GeneTree; ENSGT00940000161339; -.
DR InParanoid; Q7YS44; -.
DR OMA; SIPWLFL; -.
DR OrthoDB; 405736at2759; -.
DR Proteomes; UP000002277; Chromosome 1.
DR Bgee; ENSPTRG00000001670; Expressed in liver and 11 other tissues.
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:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
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:0034899; F:trimethylamine monooxygenase activity; IEA:UniProtKB-EC.
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; IPR002255; Flavin_mOase_3.
DR Pfam; PF00743; FMO-like; 1.
DR PIRSF; PIRSF000332; FMO; 1.
DR PRINTS; PR00370; FMOXYGENASE.
DR PRINTS; PR01123; FMOXYGENASE3.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 3: Inferred from homology;
KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..532
FT /note="Dimethylaniline monooxygenase [N-oxide-forming] 3"
FT /id="PRO_0000147657"
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; 60052 MW; 11B75102F9A7DD66 CRC64;
MGKKVAIIGA GVSGLASIRS CLEEGLEPTC FEKSNDIGGL WKFSDHAEEG RASIYKSVFS
NSSKEMMCFP DFPFPDDFPN FMHNSKIQEY IIAFAKEKNL LKYIQFKTFV SSVNKRPDFA
TTGQWDVTTE RDGKKESAVF DAVMVCSGHH VYPNLPKESF PGLNHFKGKC FHSRDYKEPG
VFNGKRVLVV GLGNSGCDIA TELSRTAEQV MISSRSGSWV MSRVWDNGYP WDMLLVTRFG
TFLKNNLPTA ISDWLYVKQM NARFKHENYG LMPLNGVLRK EPVFNDELPA SILCGIVSVK
PNVKEFTETS AIFEDGTIFE GIDCVIFATG YSFAYPFLDE SIIKSRNNEI ILFKGVFPPL
LEKSTIAVIG FVQSLGAAIP TVDLQSRWAA QVIKGTCTLP SMEDMMNDIN EKMEKKRKWF
GKSETIQTDY IVYMDELSSF IGAKPNIPWL FLTDPKLAME VYFGPCSPYQ FRLVGPGQWP
GARNAILTQW DRSLKPMQTR VVGRLQKPCF FFHWLKLFAI PILLIAVFLV LT
