FMO4_HUMAN
ID FMO4_HUMAN Reviewed; 558 AA.
AC P31512; Q53XR0;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Dimethylaniline monooxygenase [N-oxide-forming] 4;
DE EC=1.14.13.8;
DE AltName: Full=Dimethylaniline oxidase 4;
DE AltName: Full=Hepatic flavin-containing monooxygenase 4;
DE Short=FMO 4;
GN Name=FMO4; Synonyms=FMO2;
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 [MRNA].
RC TISSUE=Liver;
RX PubMed=1417778; DOI=10.1042/bj2870261;
RA Dolphin C.T., Shephard E.A., Povey S., Smith R.L., Phillips I.R.;
RT "Cloning, primary sequence and chromosomal localization of human FMO2, a
RT new member of the flavin-containing mono-oxygenase family.";
RL Biochem. J. 287:261-267(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-323; SER-372; LEU-536
RP AND ARG-544.
RG NIEHS SNPs program;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP VARIANTS THR-37; ALA-323 AND GLN-339.
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).
RN [9]
RP VARIANT HIS-28.
RX PubMed=28940097; DOI=10.1007/s00439-017-1843-2;
RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A.,
RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M.,
RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A.,
RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S.,
RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T.,
RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C.,
RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M.,
RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.;
RT "Expanding the genetic heterogeneity of intellectual disability.";
RL Hum. Genet. 136:1419-1429(2017).
RN [10]
RP ERRATUM OF PUBMED:28940097.
RX PubMed=29288388; DOI=10.1007/s00439-017-1859-7;
RA Anazi S., Maddirevula S., Salpietro V., Asi Y.T., Alsahli S., Alhashem A.,
RA Shamseldin H.E., AlZahrani F., Patel N., Ibrahim N., Abdulwahab F.M.,
RA Hashem M., Alhashmi N., Al Murshedi F., Al Kindy A., Alshaer A.,
RA Rumayyan A., Al Tala S., Kurdi W., Alsaman A., Alasmari A., Banu S.,
RA Sultan T., Saleh M.M., Alkuraya H., Salih M.A., Aldhalaan H., Ben-Omran T.,
RA Al Musafri F., Ali R., Suleiman J., Tabarki B., El-Hattab A.W., Bupp C.,
RA Alfadhel M., Al Tassan N., Monies D., Arold S.T., Abouelhoda M.,
RA Lashley T., Houlden H., Faqeih E., Alkuraya F.S.;
RT "Correction to: Expanding the genetic heterogeneity of intellectual
RT disability.";
RL Hum. Genet. 137:105-109(2018).
CC -!- FUNCTION: This protein is involved in the oxidative metabolism of a
CC variety of xenobiotics such as drugs and pesticides.
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;
CC -!- INTERACTION:
CC P31512; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-17589491, EBI-17589229;
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:Q8K4B7}; Single-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8K4B7}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver.
CC -!- SIMILARITY: Belongs to the FMO family. {ECO:0000305}.
CC -!- CAUTION: Was originally termed FMO2. {ECO:0000305|PubMed:1417778}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fmo4/";
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DR EMBL; Z11737; CAA77797.1; -; mRNA.
DR EMBL; AY882422; AAW56938.1; -; Genomic_DNA.
DR EMBL; BT007444; AAP36112.1; -; mRNA.
DR EMBL; AL031274; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW90896.1; -; Genomic_DNA.
DR EMBL; BC002780; AAH02780.1; -; mRNA.
DR CCDS; CCDS1295.1; -.
DR PIR; S29125; S29125.
DR RefSeq; NP_002013.1; NM_002022.2.
DR AlphaFoldDB; P31512; -.
DR SMR; P31512; -.
DR BioGRID; 108616; 2.
DR IntAct; P31512; 1.
DR STRING; 9606.ENSP00000356723; -.
DR ChEMBL; CHEMBL3542432; -.
DR iPTMnet; P31512; -.
DR PhosphoSitePlus; P31512; -.
DR BioMuta; FMO4; -.
DR DMDM; 399506; -.
DR jPOST; P31512; -.
DR MassIVE; P31512; -.
DR PaxDb; P31512; -.
DR PeptideAtlas; P31512; -.
DR PRIDE; P31512; -.
DR ProteomicsDB; 54792; -.
DR Antibodypedia; 34378; 108 antibodies from 22 providers.
DR DNASU; 2329; -.
DR Ensembl; ENST00000367749.4; ENSP00000356723.3; ENSG00000076258.10.
DR GeneID; 2329; -.
DR KEGG; hsa:2329; -.
DR MANE-Select; ENST00000367749.4; ENSP00000356723.3; NM_002022.3; NP_002013.1.
DR UCSC; uc001gho.4; human.
DR CTD; 2329; -.
DR DisGeNET; 2329; -.
DR GeneCards; FMO4; -.
DR HGNC; HGNC:3772; FMO4.
DR HPA; ENSG00000076258; Group enriched (kidney, liver).
DR MIM; 136131; gene.
DR neXtProt; NX_P31512; -.
DR OpenTargets; ENSG00000076258; -.
DR PharmGKB; PA28188; -.
DR VEuPathDB; HostDB:ENSG00000076258; -.
DR eggNOG; KOG1399; Eukaryota.
DR GeneTree; ENSGT00940000160256; -.
DR HOGENOM; CLU_006909_8_2_1; -.
DR InParanoid; P31512; -.
DR OMA; SHYLKVW; -.
DR OrthoDB; 405736at2759; -.
DR PhylomeDB; P31512; -.
DR TreeFam; TF105285; -.
DR BRENDA; 1.14.13.8; 2681.
DR PathwayCommons; P31512; -.
DR SignaLink; P31512; -.
DR BioGRID-ORCS; 2329; 9 hits in 1068 CRISPR screens.
DR ChiTaRS; FMO4; human.
DR GeneWiki; FMO4; -.
DR GenomeRNAi; 2329; -.
DR Pharos; P31512; Tbio.
DR PRO; PR:P31512; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P31512; protein.
DR Bgee; ENSG00000076258; Expressed in nephron tubule and 133 other tissues.
DR Genevisible; P31512; HS.
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; NAS:UniProtKB.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl.
DR GO; GO:0046322; P:negative regulation of fatty acid oxidation; IEA:Ensembl.
DR GO; GO:0042178; P:xenobiotic catabolic process; IEA:Ensembl.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR000960; Flavin_mOase.
DR InterPro; IPR020946; Flavin_mOase-like.
DR InterPro; IPR002256; Flavin_mOase_4.
DR Pfam; PF00743; FMO-like; 1.
DR PIRSF; PIRSF000332; FMO; 1.
DR PRINTS; PR00370; FMOXYGENASE.
DR PRINTS; PR01124; FMOXYGENASE4.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; FAD; Flavoprotein; Membrane; Microsome;
KW Monooxygenase; NADP; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..558
FT /note="Dimethylaniline monooxygenase [N-oxide-forming] 4"
FT /id="PRO_0000147660"
FT TRANSMEM 517..537
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 195..198
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9HFE4"
FT VARIANT 28
FT /note="P -> H (found in a patient with intellectual
FT disability; unknown pathological significance;
FT dbSNP:rs866374389)"
FT /evidence="ECO:0000269|PubMed:28940097"
FT /id="VAR_084652"
FT VARIANT 37
FT /note="I -> T (in dbSNP:rs72549338)"
FT /evidence="ECO:0000269|PubMed:12527699"
FT /id="VAR_015367"
FT VARIANT 308
FT /note="T -> S (in dbSNP:rs3737925)"
FT /id="VAR_049090"
FT VARIANT 323
FT /note="V -> A (in dbSNP:rs1042767)"
FT /evidence="ECO:0000269|PubMed:12527699, ECO:0000269|Ref.2"
FT /id="VAR_015368"
FT VARIANT 339
FT /note="E -> Q (in dbSNP:rs61342270)"
FT /evidence="ECO:0000269|PubMed:12527699"
FT /id="VAR_015369"
FT VARIANT 372
FT /note="G -> S (in dbSNP:rs45599742)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_022305"
FT VARIANT 536
FT /note="F -> L (in dbSNP:rs45487792)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_022306"
FT VARIANT 544
FT /note="L -> R (in dbSNP:rs45528740)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_022307"
SQ SEQUENCE 558 AA; 63343 MW; 6981AE9180C07802 CRC64;
MAKKVAVIGA GVSGLSSIKC CVDEDLEPTC FERSDDIGGL WKFTESSKDG MTRVYKSLVT
NVCKEMSCYS DFPFHEDYPN FMNHEKFWDY LQEFAEHFDL LKYIQFKTTV CSITKRPDFS
ETGQWDVVTE TEGKQNRAVF DAVMVCTGHF LNPHLPLEAF PGIHKFKGQI LHSQEYKIPE
GFQGKRVLVI GLGNTGGDIA VELSRTAAQV LLSTRTGTWV LGRSSDWGYP YNMMVTRRCC
SFIAQVLPSR FLNWIQERKL NKRFNHEDYG LSITKGKKAK FIVNDELPNC ILCGAITMKT
SVIEFTETSA VFEDGTVEEN IDVVIFTTGY TFSFPFFEEP LKSLCTKKIF LYKQVFPLNL
ERATLAIIGL IGLKGSILSG TELQARWVTR VFKGLCKIPP SQKLMMEATE KEQLIKRGVF
KDTSKDKFDY IAYMDDIAAC IGTKPSIPLL FLKDPRLAWE VFFGPCTPYQ YRLMGPGKWD
GARNAILTQW DRTLKPLKTR IVPDSSKPAS MSHYLKAWGA PVLLASLLLI CKSSLFLKLV
RDKLQDRMSP YLVSLWRG
