FMO6_HUMAN
ID FMO6_HUMAN Reviewed; 539 AA.
AC O60774;
DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Putative dimethylaniline monooxygenase [N-oxide-forming] 6;
DE EC=1.14.13.8;
DE AltName: Full=Dimethylaniline oxidase 6;
DE AltName: Full=Flavin-containing monooxygenase 6;
DE Short=FMO 6;
GN Name=FMO6P; Synonyms=FMO6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP ANALYSIS OF SPLICE VARIANTS.
RX PubMed=12130684; DOI=10.1124/mol.62.2.320;
RA Hines R.N., Hopp K.A., Franco J., Saeian K., Begun F.P.;
RT "Alternative processing of the human FMO6 gene renders transcripts
RT incapable of encoding a functional flavin-containing monooxygenase.";
RL Mol. Pharmacol. 62:320-325(2002).
RN [3]
RP VARIANTS ILE-127 AND ILE-257, AND POLYMORPHISM IN POSITION 105.
RX PubMed=12527699; DOI=10.1124/dmd.31.2.187;
RA Furnes B., Feng J., Sommer S.S., Schlenk D.;
RT "Identification of novel variants of the flavin-containing monooxygenase
RT gene family in African Americans.";
RL Drug Metab. Dispos. 31:187-193(2003).
CC -!- FUNCTION: It is probable that this protein is only produced in very
CC small quantity or not at all as the gene coding for it seems to be
CC unable to produce full-length transcripts.
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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000250}; Single-pass
CC membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250}; Single-pass membrane protein {ECO:0000255}.
CC -!- POLYMORPHISM: There are two alleles; one major, FMO6X105 (truncated
CC form) and one minor, FMO6Q105, (shown here) (full-length form similar
CC to the protein found in other mammals) (PubMed:12527699). A nonsense
CC mutation transforms the Gln-105 into a premature stop codon
CC (PubMed:12527699). The truncated protein is catalytically inactive
CC (PubMed:12527699). {ECO:0000269|PubMed:12527699}.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
CC -!- CAUTION: Could be the product of a pseudogene. {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; AL021026; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; O60774; -.
DR SMR; O60774; -.
DR STRING; 9606.ENSP00000236166; -.
DR iPTMnet; O60774; -.
DR PhosphoSitePlus; O60774; -.
DR BioMuta; HGNC:24024; -.
DR jPOST; O60774; -.
DR MassIVE; O60774; -.
DR PaxDb; O60774; -.
DR PeptideAtlas; O60774; -.
DR PRIDE; O60774; -.
DR UCSC; uc057ngh.1; human.
DR GeneCards; FMO6P; -.
DR HGNC; HGNC:24024; FMO6P.
DR neXtProt; NX_O60774; -.
DR PharmGKB; PA142671753; -.
DR eggNOG; KOG1399; Eukaryota.
DR InParanoid; O60774; -.
DR PhylomeDB; O60774; -.
DR TreeFam; TF105285; -.
DR PathwayCommons; O60774; -.
DR Pharos; O60774; Tdark.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; O60774; protein.
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 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 5: Uncertain;
KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..539
FT /note="Putative dimethylaniline monooxygenase [N-oxide-
FT forming] 6"
FT /id="PRO_0000147669"
FT TRANSMEM 518..538
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 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 VARIANT 127
FT /note="V -> I (in dbSNP:rs61731844)"
FT /evidence="ECO:0000269|PubMed:12527699"
FT /id="VAR_015371"
FT VARIANT 257
FT /note="V -> I (in dbSNP:rs2272797)"
FT /evidence="ECO:0000269|PubMed:12527699"
FT /id="VAR_015372"
SQ SEQUENCE 539 AA; 61291 MW; 8E0D15CA4F79FF0C CRC64;
MSKRVGIIGA GVSGLAAIWC CLEEGLEPTC FERSDDVGGL WKFSDHTEEG RASIYQSVFT
NSSKEMMCFP DFPYPDDYPN YIHHSKLQEY IKTYAQKKDL LRYIQFETLV SGIKKCPSFL
VTGQWVVVTE KDGKQESTIF DAVMICSGHH VYPNLPTDSF PGLDQFRGNY LHSRDYKNPE
AFKGKRVLVI GLGNSGSDIA VELSRLATQV IISTRSASWV MSRVWDDGYP WDMMYVTRFA
SFLRNVLPSF ISDWLYVQKM NTWFKHENYG LMPLNGSLRK EPVFNDELPS RILCGTLSIK
PSVKEFTETS AVFEDGTMFE AIDSVIFATG YDYSYPFLDE TIMKSRNNEV TLFKGIFPPL
MEKPTLAVIG LVQSLGAAIP TADLQAWWAA KVFANSCTLP TTNEMMDDTD EKMGKKLKCM
FSSFFMFGQS QTLQTDYITY VDELGSFIGA KPNIPWLFLT DPRLALEVYF GPCSPYQFRL
MGPGKWDGAR NAILTQWNRT VKPTRTRVVS EVQRPHPFYN LLKMLSFPLL LLAVTLTFY
