ID G1TNL3_RABIT Unreviewed; 535 AA.
AC G1TNL3;
DT 19-OCT-2011, integrated into UniProtKB/TrEMBL.
DT 11-DEC-2019, sequence version 2.
DT 27-MAR-2024, entry version 69.
DE RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] {ECO:0000256|PIRNR:PIRNR000332};
DE EC=1.14.13.148 {ECO:0000256|PIRNR:PIRNR000332};
DE EC=1.14.13.8 {ECO:0000256|PIRNR:PIRNR000332};
GN Name=FMO1 {ECO:0000313|Ensembl:ENSOCUP00000018588.2};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986 {ECO:0000313|Ensembl:ENSOCUP00000018588.2, ECO:0000313|Proteomes:UP000001811};
RN [1] {ECO:0000313|Ensembl:ENSOCUP00000018588.2, ECO:0000313|Proteomes:UP000001811}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke inbred {ECO:0000313|Ensembl:ENSOCUP00000018588.2,
RC ECO:0000313|Proteomes:UP000001811};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSOCUP00000018588.2}
RP IDENTIFICATION.
RC STRAIN=Thorbecke {ECO:0000313|Ensembl:ENSOCUP00000018588.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Broad spectrum monooxygenase that catalyzes the oxygenation
CC of a wide variety of nitrogen- and sulfur-containing compounds
CC including xenobiotics. Catalyzes the S-oxygenation of hypotaurine to
CC produce taurine, an organic osmolyte involved in cell volume regulation
CC as well as a variety of cytoprotective and developmental processes. In
CC vitro, catalyzes the N-oxygenation of trimethylamine (TMA) to produce
CC trimethylamine N-oxide (TMAO) and could therefore participate to the
CC detoxification of this compound that is generated by the action of gut
CC microbiota from dietary precursors such as choline, choline containing
CC compounds, betaine or L-carnitine. {ECO:0000256|PIRNR:PIRNR000332}.
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:0000256|ARBA:ARBA00000700};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24469;
CC Evidence={ECO:0000256|ARBA:ARBA00000700};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hypotaurine + NADH + O2 = H2O + NAD(+) + taurine;
CC Xref=Rhea:RHEA:74111, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57540, ChEBI:CHEBI:57853,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:507393; EC=1.14.13.8;
CC Evidence={ECO:0000256|ARBA:ARBA00034447};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:74112;
CC Evidence={ECO:0000256|ARBA:ARBA00034447};
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:0000256|ARBA:ARBA00034434};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69820;
CC Evidence={ECO:0000256|ARBA:ARBA00034434};
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:0000256|ARBA:ARBA00034415};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31980;
CC Evidence={ECO:0000256|ARBA:ARBA00034415};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000256|ARBA:ARBA00001974,
CC ECO:0000256|PIRNR:PIRNR000332, ECO:0000256|RuleBase:RU361177};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000256|PIRNR:PIRNR000332}.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000256|ARBA:ARBA00009183,
CC ECO:0000256|PIRNR:PIRNR000332, ECO:0000256|RuleBase:RU361177}.
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DR EMBL; AAGW02000079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02000080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02000081; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; G1TNL3; -.
DR SMR; G1TNL3; -.
DR Ensembl; ENSOCUT00000022793.3; ENSOCUP00000018588.2; ENSOCUG00000002788.4.
DR GeneTree; ENSGT00940000160945; -.
DR HOGENOM; CLU_006909_8_2_1; -.
DR InParanoid; G1TNL3; -.
DR TreeFam; TF105285; -.
DR Proteomes; UP000001811; Chromosome 13.
DR Bgee; ENSOCUG00000002788; Expressed in liver and 15 other cell types or tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-UniRule.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0034899; F:trimethylamine monooxygenase activity; IEA:RHEA.
DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl.
DR GO; GO:0070995; P:NADPH oxidation; IEA:Ensembl.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; IEA:Ensembl.
DR GO; GO:0042412; P:taurine biosynthetic process; IEA:Ensembl.
DR GO; GO:0009404; P:toxin metabolic process; IEA:Ensembl.
DR GO; GO:0006805; P:xenobiotic metabolic process; IEA:Ensembl.
DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR000960; Flavin_mOase.
DR InterPro; IPR020946; Flavin_mOase-like.
DR InterPro; IPR002253; Flavin_mOase_1.
DR PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1.
DR PANTHER; PTHR23023:SF154; DIMETHYLANILINE MONOOXYGENASE [N-OXIDE-FORMING] 1; 1.
DR Pfam; PF00743; FMO-like; 1.
DR PIRSF; PIRSF000332; FMO; 1.
DR PRINTS; PR00370; FMOXYGENASE.
DR PRINTS; PR01121; FMOXYGENASE1.
DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 3.
PE 3: Inferred from homology;
KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824,
KW ECO:0000256|PIRNR:PIRNR000332};
KW FAD {ECO:0000256|ARBA:ARBA00022827, ECO:0000256|PIRNR:PIRNR000332};
KW Flavoprotein {ECO:0000256|ARBA:ARBA00022630,
KW ECO:0000256|PIRNR:PIRNR000332};
KW Membrane {ECO:0000256|PIRNR:PIRNR000332, ECO:0000256|SAM:Phobius};
KW Monooxygenase {ECO:0000256|ARBA:ARBA00023033,
KW ECO:0000256|PIRNR:PIRNR000332};
KW NADP {ECO:0000256|ARBA:ARBA00022857, ECO:0000256|PIRNR:PIRNR000332};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002,
KW ECO:0000256|PIRNR:PIRNR000332};
KW Reference proteome {ECO:0000313|Proteomes:UP000001811};
KW Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius}.
FT TRANSMEM 423..441
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 453..471
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT TRANSMEM 517..534
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
SQ SEQUENCE 535 AA; 60869 MW; 1FD43DEDA9909003 CRC64;
MAKRVAIVGA GVSGLASIKC CLEEGLEPTC FERSDDLGGL WRFTEHVEEG RASLYKSVVS
NSCKEMSCYS DFPFPEDYPN YVPNSQFLDY LKMYADRFDL LKCIQFKTTV FSITKCQDFN
VSGQWEVVTL HEGKQESAIF DAVMVCTGFL TNPHLPLGCF PGIKTFKGQY FHSRQYKHPD
IFKDKRVLVV GMGNSGTDIA VEASHVAKKV FLSTTGGAWV ISRVFDSGYP WDMVFTTRFQ
NFIRNSLPTP IVTWLVAKKM NSWFNHANYG LVPKDRIQLK EPVLNDELPG RIITGKVFIR
PSIKEVKENS VVFGNAHNTP SEEPIDVIVF ATGYTFAFPF LDESVVKVED GQASLYKYIF
PAHLQKPTLA VIGLIKPLGS MLPTGETQAR YTVQVFKGVI KLPPTSVMIK EVNERKENKH
NGLLAFFLFF FFYFSTQRNI LFKEYKLHAF HKYNFRNIVI LPTIPFLPST LPPHFFLPLT
PRKWKGARNA IMTQWDRTFK VTKTRIVQES SSPFESLLKL FAVLALLVSV FLIFL
//
