ID   FMO2_MOUSE              Reviewed;         535 AA.
AC   Q8K2I3; Q9QZF7;
DT   25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 2 {ECO:0000305};
DE            EC=1.14.13.- {ECO:0000269|PubMed:18930751};
DE   AltName: Full=Dimethylaniline oxidase 2;
DE   AltName: Full=Pulmonary flavin-containing monooxygenase 2;
DE            Short=FMO 2;
GN   Name=Fmo2 {ECO:0000312|MGI:MGI:1916776};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
RX   PubMed=11835629; DOI=10.1002/jbt.10009;
RA   Karoly E.D., Rose R.L.;
RT   "Sequencing, expression, and characterization of cDNA expressed flavin-
RT   containing monooxygenase 2 from mouse.";
RL   J. Biochem. Mol. Toxicol. 15:300-308(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II; TISSUE=Mammary tumor;
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   FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=18930751; DOI=10.1016/j.taap.2008.09.017;
RA   Henderson M.C., Siddens L.K., Morre J.T., Krueger S.K., Williams D.E.;
RT   "Metabolism of the anti-tuberculosis drug ethionamide by mouse and human
RT   FMO1, FMO2 and FMO3 and mouse and human lung microsomes.";
RL   Toxicol. Appl. Pharmacol. 233:420-427(2008).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Heart, Kidney, Lung, and Pancreas;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Catalyzes the oxidative metabolism of numerous xenobiotics,
CC       including mainly therapeutic drugs and insecticides that contain a soft
CC       nucleophile, most commonly nitrogen and sulfur and participates to
CC       their bioactivation (PubMed:18930751). Catalyzes the S-oxygenation of
CC       the prodrug ethionamide (ETA) to the S-oxide (ETASO), the first step in
CC       its bioactivation following by the second oxygenation to the sulfinic
CC       acid but to a lesser extend (PubMed:18930751).
CC       {ECO:0000269|PubMed:18930751}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2131 uM for ethionamide {ECO:0000269|PubMed:18930751};
CC       pH dependence:
CC         Optimum pH is 10.5.;
CC   -!- SUBCELLULAR LOCATION: Microsome membrane
CC       {ECO:0000250|UniProtKB:P17635}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:P17635}. Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P17635}; Single-pass membrane protein
CC       {ECO:0000250|UniProtKB:P17635}.
CC   -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
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DR   EMBL; AF184981; AAD56413.1; -; mRNA.
DR   EMBL; BC031415; AAH31415.1; -; mRNA.
DR   CCDS; CCDS15425.1; -.
DR   RefSeq; NP_061369.2; NM_018881.3.
DR   RefSeq; XP_006497012.1; XM_006496949.3.
DR   AlphaFoldDB; Q8K2I3; -.
DR   SMR; Q8K2I3; -.
DR   BioGRID; 207761; 5.
DR   STRING; 10090.ENSMUSP00000044405; -.
DR   iPTMnet; Q8K2I3; -.
DR   PhosphoSitePlus; Q8K2I3; -.
DR   jPOST; Q8K2I3; -.
DR   MaxQB; Q8K2I3; -.
DR   PaxDb; 10090-ENSMUSP00000044405; -.
DR   PeptideAtlas; Q8K2I3; -.
DR   ProteomicsDB; 267373; -.
DR   Antibodypedia; 34377; 173 antibodies from 25 providers.
DR   DNASU; 55990; -.
DR   Ensembl; ENSMUST00000045902.13; ENSMUSP00000044405.7; ENSMUSG00000040170.14.
DR   Ensembl; ENSMUST00000111510.8; ENSMUSP00000107135.2; ENSMUSG00000040170.14.
DR   GeneID; 55990; -.
DR   KEGG; mmu:55990; -.
DR   UCSC; uc007dgz.1; mouse.
DR   AGR; MGI:1916776; -.
DR   CTD; 2327; -.
DR   MGI; MGI:1916776; Fmo2.
DR   VEuPathDB; HostDB:ENSMUSG00000040170; -.
DR   eggNOG; KOG1399; Eukaryota.
DR   GeneTree; ENSGT00940000161099; -.
DR   HOGENOM; CLU_006909_8_2_1; -.
DR   InParanoid; Q8K2I3; -.
DR   OMA; QTNHIDY; -.
DR   OrthoDB; 2079054at2759; -.
DR   PhylomeDB; Q8K2I3; -.
DR   TreeFam; TF105285; -.
DR   BRENDA; 1.14.13.8; 3474.
DR   Reactome; R-MMU-217271; FMO oxidises nucleophiles.
DR   BioGRID-ORCS; 55990; 1 hit in 78 CRISPR screens.
DR   ChiTaRS; Fmo2; mouse.
DR   PRO; PR:Q8K2I3; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q8K2I3; Protein.
DR   Bgee; ENSMUSG00000040170; Expressed in lumbar dorsal root ganglion and 184 other cell types or tissues.
DR   ExpressionAtlas; Q8K2I3; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; 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; IDA:MGI.
DR   GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; ISO:MGI.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0097009; P:energy homeostasis; IGI:MGI.
DR   GO; GO:0006739; P:NADP metabolic process; ISO:MGI.
DR   GO; GO:0070995; P:NADPH oxidation; ISS:UniProtKB.
DR   GO; GO:0046322; P:negative regulation of fatty acid oxidation; IGI:MGI.
DR   GO; GO:0006082; P:organic acid metabolic process; ISO:MGI.
DR   GO; GO:0072592; P:oxygen metabolic process; IDA:MGI.
DR   GO; GO:0009404; P:toxin metabolic process; ISO:MGI.
DR   GO; GO:0006805; P:xenobiotic metabolic process; ISO:MGI.
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; IPR002254; Flavin_mOase_2.
DR   PANTHER; PTHR23023; DIMETHYLANILINE MONOOXYGENASE; 1.
DR   PANTHER; PTHR23023:SF84; FLAVIN-CONTAINING MONOOXYGENASE 2; 1.
DR   Pfam; PF00743; FMO-like; 1.
DR   PIRSF; PIRSF000332; FMO; 1.
DR   PRINTS; PR00370; FMOXYGENASE.
DR   PRINTS; PR01122; FMOXYGENASE2.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 2.
DR   Genevisible; Q8K2I3; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Endoplasmic reticulum; FAD; Flavoprotein; Isopeptide bond;
KW   Magnesium; Membrane; Microsome; Monooxygenase; NADP; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P17635"
FT   CHAIN           2..535
FT                   /note="Dimethylaniline monooxygenase [N-oxide-forming] 2"
FT                   /id="PRO_0000147648"
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         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P17635"
FT   CROSSLNK        492
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO)"
FT                   /evidence="ECO:0000250|UniProtKB:Q99518"
FT   CONFLICT        169
FT                   /note="Q -> R (in Ref. 1; AAD56413)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   535 AA;  60974 MW;  705FAD9D8EADB1B1 CRC64;
     MAKKVVVIGA GVSGLISLKC CVDEGLEPTC FERTEDIGGL WRFKENVEDG RASIYRSVIT
     NTSKEMSCFS DFPMPEDFPN FLHNSKLLEY FRIFAKKFDL LKYIQFQTTV ISVKKRPDFA
     SSGQWEVYTQ SNGKEQRTVF DAVMVCSGHH IQPHLPLKSF PGIERFRGQY FHSREYKHPV
     GFEGKRILVV GIGNSAADIA SELSKTAAQV FVSTRHGSWV MSRISEDGYP WDMVFHTRFS
     SMLRNVLPRT VVKWMMEQQM NRWFNHENYG LVPQNKYLMK EPVLNDDLPS RLLYGAIKVK
     TRVKELTETA VVFEDGTVEE DVDIIVFATG YTFSFSFLED SLVKVEDNRV SLYKAMFPPH
     LEKPTLACIG LIQPLGSIFP TVELQARWAT RVFKGLCSLP SETTMMADIV ERNEKRVNLF
     GKSQSQILQT NYVDYLDELA LEIGAKPDFV SLFFKDPKLA VKLYFGPCNS YQYRLVGPGQ
     WEGARNAILT QKQRILKPLK TRTLQSSDSA PVSFLLKILG LLAVVLAFFF QLQGF
//