UniProtKB - P17635 (FMO2_RABIT)
Dimethylaniline monooxygenase [N-oxide-forming] 2
FMO2
Functioni
Catalyzes the oxidative metabolism of numerous xenobiotics, including mainly therapeutic drugs and insecticides that contain a soft nucleophile, most commonly nitrogen and sulfur and participates to their bioactivation (PubMed:3785145, PubMed:10950853, PubMed:16620765, PubMed:11302936, PubMed:15144220, PubMed:15294458).
Most drug substrates are tertiary amines such as prochlorperazine and trifluoperazine which are N-oxygenated to form the N-oxide, or sulfides such as thiourea and ethionamide, which are S-oxygenated to the sulfoxide (PubMed:3785145, PubMed:15144220, PubMed:16620765).
Others include primary alkylamines such as N-dodecylamine and octan-1-amine that are sequentially monooxygenated to oximes through intermediate hydroxylamines and both steps are NADPH- and oxygen-dependent (PubMed:3785145).
Also metabolized N-Deacetyl ketoconazole (DAK) to N-hydroxy-DAK and appears to further metabolizes N-hydroxy-DAK to two others metabolites (PubMed:10950853).
Also catalyzes S-oxygenation of the thioether-containing organophosphate insecticides, phorate and disulfoton (PubMed:15294458).
6 PublicationsCatalytic activityi
Cofactori
Protein has several cofactor binding sites:Kineticsi
- KM=36 µM for thiourea1 Publication
- KM=21 µM for ethylenethiourea1 Publication
- KM=82 µM for N-phenylthiourea1 Publication
- KM=25 µM for ANTU1 Publication
- KM=310 µM for N,N-dimethylaniline1 Publication
- KM=500 µM for (S)-nicotine1 Publication
- KM=330 µM for N,N-dimethylaniline1 Publication
- KM=46 µM for N,N-dimethyloctylamine1 Publication
- KM=31 µM for trifluoperazine1 Publication
- KM=1000 µM for desmethylperazine1 Publication
- KM=120 µM for N-methyloctylamine1 Publication
- KM=17 µM for N-methyloctylhydroxylamine1 Publication
- KM=12000 µM for octan-1-amine1 Publication
- KM=290 µM for N-dodecylamine1 Publication
- KM=70 µM for N-methyloctylhydroxylamine1 Publication
- KM=3 µM for N-dodecylhydroxylamine1 Publication
- KM=57 µM for phorate1 Publication
- KM=32 µM for disulfoton1 Publication
- Vmax=450 nmol/min/mg enzyme toward N,N-dimethylaniline1 Publication
- Vmax=450 nmol/min/mg enzyme toward N,N-dimethyloctylamine1 Publication
- Vmax=450 nmol/min/mg enzyme toward trifluoperazine1 Publication
- Vmax=900 nmol/min/mg enzyme toward desmethylperazine 11 Publication
- Vmax=550 nmol/min/mg enzyme toward N-methyloctylamine1 Publication
- Vmax=500 nmol/min/mg enzyme toward N-methyloctylhydroxylamine1 Publication
- Vmax=1600 nmol/min/mg enzyme toward octan-1-amine1 Publication
- Vmax=1600 nmol/min/mg enzyme toward N-dodecylamine1 Publication
- Vmax=600 nmol/min/mg enzyme toward N-methyloctylhydroxylamine1 Publication
- Vmax=600 nmol/min/mg enzyme toward N-dodecylhydroxylamine1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 32 | FADBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 9 – 13 | FADBy similarity | 5 | |
Nucleotide bindingi | 40 – 41 | FADBy similarity | 2 | |
Nucleotide bindingi | 60 – 61 | NADPBy similarity | 2 | |
Nucleotide bindingi | 61 – 62 | FADBy similarity | 2 | |
Nucleotide bindingi | 195 – 198 | NADPBy similarity | 4 |
GO - Molecular functioni
- flavin adenine dinucleotide binding Source: InterPro
- N,N-dimethylaniline monooxygenase activity Source: UniProtKB-EC
- NADP binding Source: InterPro
GO - Biological processi
- NADPH oxidation Source: UniProtKB
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Ligand | FAD, Flavoprotein, Magnesium, NADP |
Enzyme and pathway databases
BRENDAi | 1.14.13.8, 1749 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:FMO2By similarity |
Organismi | Oryctolagus cuniculus (Rabbit) |
Taxonomic identifieri | 9986 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus |
Proteomesi |
|
Subcellular locationi
Endoplasmic reticulum
- Microsome membrane 1 Publication; Single-pass membrane protein 1 Publication
- Endoplasmic reticulum membrane 1 Publication; Single-pass membrane protein 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 510 – 530 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, MicrosomePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 510 – 535 | Missing : Increases protein solubility in the absence of detergent. 1 PublicationAdd BLAST | 26 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000147650 | 2 – 535 | Dimethylaniline monooxygenase [N-oxide-forming] 2Add BLAST | 534 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanine1 Publication | 1 | |
Cross-linki | 492 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity |
Keywords - PTMi
Acetylation, Isopeptide bond, Ubl conjugationProteomic databases
PRIDEi | P17635 |
PTM databases
iPTMneti | P17635 |
Expressioni
Tissue specificityi
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1399, Eukaryota |
InParanoidi | P17635 |
OrthoDBi | 405736at2759 |
Family and domain databases
Gene3Di | 3.50.50.60, 4 hits |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR000960, Flavin_mOase IPR020946, Flavin_mOase-like IPR002254, Flavin_mOase_2 |
Pfami | View protein in Pfam PF00743, FMO-like, 1 hit |
PIRSFi | PIRSF000332, FMO, 1 hit |
PRINTSi | PR00370, FMOXYGENASE PR01122, FMOXYGENASE2 |
SUPFAMi | SSF51905, SSF51905, 2 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MAKKVAVIGA GVSGLISLKC CVDEGLEPTC FERTEDIGGL WRFKENVEDG
60 70 80 90 100
RASIYQSVIT NTSKEMSCFS DFPMPEDFPN FLHNSKLLEY FRIFAKKFDL
110 120 130 140 150
LKYIQFQTTV ISVKKRPDFA SSGQWEVVTQ SNSKQQSAVF DAVMVCSGHH
160 170 180 190 200
ILPNIPLKSF PGIEKFKGQY FHSRQYKHPA GLEGKRILVI GIGNSASDIA
210 220 230 240 250
VELSKKAAQV YISTRKGSWV MSRISEDGYP WDMVFHTRFS SMLRNVLPRM
260 270 280 290 300
IVKWMMEQQM NRWFNHENYG LAPENKYLMK EPVLNDDLPS RILYGTIKVK
310 320 330 340 350
RRVKELTESA AIFEDGTVEE DIDVIVFATG YTFAFPFLEE SLVKIEDNMV
360 370 380 390 400
SLYKYMFPPQ LEKSTFACLG LIQPLGSIFP TVELQARWAT RVFKGLCSLP
410 420 430 440 450
SKETMMADII KRNENRIALF GESLSQKLQT NYIDYLDELA LEIGAKPDLV
460 470 480 490 500
SFLFKDPKLA VKLYFGPCNS YQYRLVGPGQ WEGARNAIFT QKQRILKPLK
510 520 530
TRTLKASSNF PVSFLLKFLG LFALVLAFLF QLQWF
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 120 | A → S in PFMO-2 and PFMO-4. | 1 | |
Natural varianti | 136 | Q → E in PFMO-2 and PFMO-4. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M32029 mRNA Translation: AAA31442.1 |
PIRi | B35182 |
RefSeqi | NP_001075753.1, NM_001082284.1 |
Genome annotation databases
GeneIDi | 100009119 |
KEGGi | ocu:100009119 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M32029 mRNA Translation: AAA31442.1 |
PIRi | B35182 |
RefSeqi | NP_001075753.1, NM_001082284.1 |
3D structure databases
AlphaFoldDBi | P17635 |
SMRi | P17635 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9986.ENSOCUP00000004486 |
PTM databases
iPTMneti | P17635 |
Proteomic databases
PRIDEi | P17635 |
Genome annotation databases
GeneIDi | 100009119 |
KEGGi | ocu:100009119 |
Organism-specific databases
CTDi | 2327 |
Phylogenomic databases
eggNOGi | KOG1399, Eukaryota |
InParanoidi | P17635 |
OrthoDBi | 405736at2759 |
Enzyme and pathway databases
BRENDAi | 1.14.13.8, 1749 |
Family and domain databases
Gene3Di | 3.50.50.60, 4 hits |
InterProi | View protein in InterPro IPR036188, FAD/NAD-bd_sf IPR000960, Flavin_mOase IPR020946, Flavin_mOase-like IPR002254, Flavin_mOase_2 |
Pfami | View protein in Pfam PF00743, FMO-like, 1 hit |
PIRSFi | PIRSF000332, FMO, 1 hit |
PRINTSi | PR00370, FMOXYGENASE PR01122, FMOXYGENASE2 |
SUPFAMi | SSF51905, SSF51905, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | FMO2_RABIT | |
Accessioni | P17635Primary (citable) accession number: P17635 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 138 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families