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PR01122

Identifier
FMOXYGENASE2  [View Relations]  [View Alignment]  
Accession
PR01122
No. of Motifs
9
Creation Date
29-APR-1999
Title
Flavin-containing monooxygenase (FMO) 2 signature
Database References
PRINTS; PR00370 FMOXYGENASE
PFAM; PF00743 FMO-like
INTERPRO; IPR002254
Literature References
1. LAWTON, M.P., CASHMAN, J.R., CRESTEIL, T., DOLPHIN, C.T., ELFARRA, A.A.,
HINES, R.N., HODGSON, E., KIMURA, T., OZOLS, J., PHILLIPS, I.R.,
PHILPOT, R.M., POULSEN, L.L., RETTIE, A.E., SHEPHARD, E.A., WILLIAMS, D.E.
AND ZIEGLER, D.M.
A nomenclature for the mammalian flavin-containing monooxygenase gene
family based on amino acid sequence identities.
ARCH.BIOCHEM.BIOPHYS. 308(19) 254-257 (1994).
 
2. DOLPHIN, C.T., SHEPHARD, E.A., POVEY, S., PALMER, C.N.A., ZIEGLER, D.M.,
AYESH, R., SMITH, R.L. AND PHILLIPS, I.R.
Cloning, primary sequence and chromosome mapping of a human flavin-
containing monooxygenase (FMO1).
J.BIOL.CHEM. 266 12379-12385 (1991).
 
3. LAWTON, M.P., GASSER, R., TYNES, R.E., HODGSON, E. AND PHILPOT, R.M.
The flavin-containing monooxygenase enzymes expressed in rabbit liver and
lung are products of related but distinctly different genes.
J.BIOL.CHEM. 265 5855-5861 (1990).
 
4. LOMRI, N., GU, Q. AND CASHMAN, J.R.
Molecular cloning of the flavin-containing monooxygenase (FORM-II) cDNA
from adult human liver.
PROC.NATL.ACAD.SCI.U.S.A. 89 1685-1689 (1992). 
 
5. DOLPHIN, C.T., SHEPHARD, E.A., POVEY, S., SMITH, R.L. AND PHILLIPS, I. R.
Cloning, primary sequence and chromosomal localisation of human FMO2, a new
member of the flavin-containing monooxygenase family.
BIOCHEM.J. 287 261-267 (1992).
 
6. ATTA-ASAFO-ADJEI, E., LAWTON, M.P. AND PHILPOT, R.M.
Cloning, sequencing, distribution and expression in E.coli of flavin-
containing monooxygenase 1C1 - evidence for a third gene family in rabbits.
J.BIOL.CHEM. 268 9681-9689 (1993).
 
7. JOHNSTON, M., ANDREWS, S., BRINKMAN, R., COOPER, J., DING, H.,
DOVER, J., DU, Z., FAVELLO, A., FULTON, L., GATTUNG, S., GEISEL, C.,
KIRSTEN, J., KUCABA, T., HILLIER, L., JIER, M., JOHNSTON, L., LANGSTON, Y.,
LATREILLE, P., LOUIS, E.J., MACRI, C., MARDIS, E., MENEZES, S., MOUSER, L.,
NHAN, M., RIFKIN, L., RILES, L., ST.PETER, H., TREVASKIS, E., VAUGHAN, K.,
VIGNATI, D., WILCOX, L., WOHLDMAN, P., WATERSTON, R., WILSON R. AND
VAUDIN M.
Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII.
SCIENCE 265 2077-2082 (1994). 
 
8. NIKBAKHT, K.N., LAWTON, M.P. AND PHILPOT, R.M.
Guinea pig or rabbit lung flavin-containing monooxygenases with distinct
mobilities in SDS-PAGE are allelic variants that differ at only two 
positions.
PHARMACOGENETICS 2 207-216 (1992).
 
9. STEHR, M., DIEKMANN, H., SMAU, L, SETH, O., GHISLA, S., SINGH, M. AND
MACHEROUX, P.
A hydrophobic sequence motif common to N-hydroxylating enzymes.
TRENDS BIOCHEM.SCI. 23 56-57 (1998).
 
10. OZOLS, J.
Covalent structure of liver microsomal flavin-containing monooxygenase 
form 1. 
J.BIOL.CHEM. 265 10289-10299 (1990).  
 
11. GUAN, S.H., FALICK, A.M., WILLIAMS, D.E. AND CASHMAN, J.R.
Evidence for complex formation between rabbit lung flavin-containing
monooxygenase and calreticulin.
BIOCHEMISTRY 30 9892-9900 (1991).

Documentation
Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-
metabolising enzymes [1]. Using an NADPH cofactor and FAD prosthetic group,
these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen,
sulphur, phosphorous and selenium atoms in a range of structurally diverse
compounds. FMOs have been implicated in the metabolism of a number of
pharmaceuticals, pesticides and toxicants. In man, lack of hepatic FMO-
catalysed trimethylamine metabolism results in trimethylaminuria (fish 
odour syndrome).
 
Five mammalian forms of FMO are now known and have been designated
FMO1-FMO5 [2-6]: this is a recent nomenclature based on comparison of
amino acid sequences, and has been introduced in an attempt to eliminate
confusion inherent in multiple, laboratory-specific designations and
tissue-based classifications [1]. Following the determination of the
complete nucleotide sequence of S.cerevisiae [7], a novel gene was found
to encode a protein with similarity to mammalian monooygenases.
 
Guinea pig and rabbit both express two variants of `lung' FMO, observed as
three distinct phenotypes based on mobility differences in SDS-PAGE [8].
The coding regions of the guinea pig variants differ at only two positions,
both of which result in amino acid substitutions [8]. Similarly, the
nucleotide and amino acid sequences of the rabbit variants differ at only
two positions. The amino sequence contains putative FAD- (GxGxxG) and NADP+-
binding (GxGxxA) sites, a `FATGY' motif that has also been observed in a 
range of siderphore biosynthetic enzymes [9], and a C-terminal hydrophobic
segment that is believed to anchor the monooxygenase to the microsomal
membrane [10].
 
The activities of the enzymes are characteristic of the lung FMO, and the
mobilities of the expressed enzymes are the same as those observed for the
variants present in guinea pig pulmonary microsomal preparations [8]. Both
rabbit and guinea pig lung FMO are associated with a single gene. Rabbit 
lung FMO exists in tight association with the calcium-binding protein, 
calreticulin [11]. It is thought that complexation of calreticulin with 
rabbit lung FMO could account for some of the unusual physical properties
of this FMO enzyme form.   
 
FMOXYGENASE2 is a 9-element fingerprint that provides a signature for type
2 flavin-containing monooxygenases. The fingerprint was derived from an
initial alignment of 3 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise type 2 FMOs but distinguish them from the rest
of the FMO family - motif 9 spans the C-terminal hydrophobic region thought
to act as a membrane anchor. A single iteration on SPTR37_9f was required to
reach convergence, no further sequences being identified beyond the starting
set. A single partial match was found, a human type 2 FMO fragment (Q99518),
which lacks the portion of sequence bearing the final 2 motifs.
Summary Information
   3 codes involving  9 elements
0 codes involving 8 elements
1 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
9333333333
8000000000
7111111100
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
FMO2_CAVPO    FMO2_MACMU    FMO2_RABIT    
True Positive Partials
Codes involving 7 elements
Q99518
Sequence Titles
FMO2_CAVPO  DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 2 (EC 1.14.13.8) (PULMONARY FLAVIN-CONTAINING MONOOXYGENASE 2) (FMO 2) (DIMETHYLANILINE OXIDASE 2) (FMO 1B1) - CAVIA PORCELLUS (GUINEA PIG). 
FMO2_MACMU DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 2 (EC 1.14.13.8) (PULMONARY FLAVIN-CONTAINING MONOOXYGENASE 2) (FMO 2) (DIMETHYLANILINE OXIDASE 2) (FMO 1B1) - MACACA MULATTA (RHESUS MACAQUE).
FMO2_RABIT DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 2 (EC 1.14.13.8) (PULMONARY FLAVIN-CONTAINING MONOOXYGENASE 2) (FMO 2) (DIMETHYLANILINE OXIDASE 2) (FMO 1B1) - ORYCTOLAGUS CUNICULUS (RABBIT).

Q99518 FLAVIN-CONTAINING MONOOXYGENASE 2 - HOMO SAPIENS (HUMAN).
Scan History
SPTR37_9f  1  4    NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
KLLEYFRIFAKKF FMO2_MACMU 85 85 -
KLLEYFRIFAKKF FMO2_RABIT 85 85 -
KLLEYFRLFAKKF FMO2_CAVPO 85 85 -

Motif 2 width=9
Element Seqn Id St Int Rpt
QTTVLSVRK FMO2_MACMU 106 8 -
QTTVISVKK FMO2_RABIT 106 8 -
QTTVLTVKK FMO2_CAVPO 106 8 -

Motif 3 width=14
Element Seqn Id St Int Rpt
PRTVVKWMIEQQMN FMO2_MACMU 247 132 -
PRMIVKWMMEQQMN FMO2_RABIT 247 132 -
PRTVSKWMMEQQLN FMO2_CAVPO 247 132 -

Motif 4 width=11
Element Seqn Id St Int Rpt
LVKVENNMVSL FMO2_MACMU 341 80 -
LVKIEDNMVSL FMO2_RABIT 341 80 -
LVKIEHNMVSL FMO2_CAVPO 341 80 -

Motif 5 width=15
Element Seqn Id St Int Rpt
DIIKRNEKRIDLFGE FMO2_MACMU 407 55 -
DIIKRNENRIALFGE FMO2_RABIT 407 55 -
DIIKRNEKRIDLFGE FMO2_CAVPO 407 55 -

Motif 6 width=13
Element Seqn Id St Int Rpt
ESQSQTLQTNYVD FMO2_MACMU 421 -1 -
ESLSQKLQTNYID FMO2_RABIT 421 -1 -
ESQSQIVQTNYVD FMO2_CAVPO 421 -1 -

Motif 7 width=15
Element Seqn Id St Int Rpt
LEIGAKPDFCSLLFK FMO2_MACMU 440 6 -
LEIGAKPDLVSFLFK FMO2_RABIT 440 6 -
LEIGAKPDLISFLLK FMO2_CAVPO 440 6 -

Motif 8 width=16
Element Seqn Id St Int Rpt
RVLKDSSNFPVSFLLK FMO2_MACMU 501 46 -
RTLKASSNFPVSFLLK FMO2_RABIT 501 46 -
RSVKAAPNLSASFLMK FMO2_CAVPO 501 46 -

Motif 9 width=14
Element Seqn Id St Int Rpt
LGLVAVVVAFFCQL FMO2_MACMU 518 1 -
LGLFALVLAFLFQL FMO2_RABIT 518 1 -
LALVAVFVAFFSQL FMO2_CAVPO 518 1 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
KLLEYFRIFAKKF FMO2_MACMU 85 85 -
KLLEYFRIFAKKF FMO2_RABIT 85 85 -
KLLEYFRLFAKKF FMO2_CAVPO 85 85 -

Motif 2 width=9
Element Seqn Id St Int Rpt
QTTVLSVRK FMO2_MACMU 106 8 -
QTTVISVKK FMO2_RABIT 106 8 -
QTTVLTVKK FMO2_CAVPO 106 8 -

Motif 3 width=14
Element Seqn Id St Int Rpt
PRTVVKWMIEQQMN FMO2_MACMU 247 132 -
PRMIVKWMMEQQMN FMO2_RABIT 247 132 -
PRTVSKWMMEQQLN FMO2_CAVPO 247 132 -

Motif 4 width=11
Element Seqn Id St Int Rpt
LVKVENNMVSL FMO2_MACMU 341 80 -
LVKIEDNMVSL FMO2_RABIT 341 80 -
LVKIEHNMVSL FMO2_CAVPO 341 80 -

Motif 5 width=15
Element Seqn Id St Int Rpt
DIIKRNEKRIDLFGE FMO2_MACMU 407 55 -
DIIKRNENRIALFGE FMO2_RABIT 407 55 -
DIIKRNEKRIDLFGE FMO2_CAVPO 407 55 -

Motif 6 width=13
Element Seqn Id St Int Rpt
ESQSQTLQTNYVD FMO2_MACMU 421 -1 -
ESLSQKLQTNYID FMO2_RABIT 421 -1 -
ESQSQIVQTNYVD FMO2_CAVPO 421 -1 -

Motif 7 width=15
Element Seqn Id St Int Rpt
LEIGAKPDFCSLLFK FMO2_MACMU 440 6 -
LEIGAKPDLVSFLFK FMO2_RABIT 440 6 -
LEIGAKPDLISFLLK FMO2_CAVPO 440 6 -

Motif 8 width=16
Element Seqn Id St Int Rpt
RVLKDSSNFPVSFLLK FMO2_MACMU 501 46 -
RTLKASSNFPVSFLLK FMO2_RABIT 501 46 -
RSVKAAPNLSASFLMK FMO2_CAVPO 501 46 -

Motif 9 width=14
Element Seqn Id St Int Rpt
LGLVAVVVAFFCQL FMO2_MACMU 518 1 -
LGLFALVLAFLFQL FMO2_RABIT 518 1 -
LALVAVFVAFFSQL FMO2_CAVPO 518 1 -