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PR01124

Identifier
FMOXYGENASE4  [View Relations]  [View Alignment]  
Accession
PR01124
No. of Motifs
10
Creation Date
29-APR-1999
Title
Flavin-containing monooxygenase (FMO) 4 signature
Database References
PRINTS; PR00370 FMOXYGENASE
PFAM; PF00743 FMO-like
INTERPRO; IPR002256
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. DOLPHIN, C.T., CULLINGFORD, T.E., SHEPHARD, E.A., SMITH, R.L. AND
PHILLIPS, I.R.
Differential developmental and tissue-specific regulation of expression of
the genes encoding three members of the flavin-containing monooxygenase
family of man, FMO1, FMO3 and FM04.
EUR.J.BIOCHEMISTRY 235 683-689(1996). 
 
9. BURNETT, V.L., LAWTON, M.P. AND PHILPOT, R.M.
Cloning and sequencing of flavin-containing monooxygenases FMO3 and FMO4
from rabbit and characterization of FMO3.
J.BIOL.CHEM. 269 14314-14322(1994). 
 
10. 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).
 
11. OZOLS, J.
Covalent structure of liver microsomal flavin-containing monooxygenase 
form 1. 
J.BIOL.CHEM. 265 10289-10299 (1990).  

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.
 
FMO4 mRNA is present in low abundance in several foetal and adult tissues
and the corresponding gene thus appears to be expressed constitutively [8].
Sequence analysis reveals that FMO4 is 56% identical to FMO3; each is
encoded by a single gene [9]. The deduced amino acid sequence of human FM04 
includes the putative FAD- (GxGxxG) and NADP+ pyrophosphate-binding (GxGxxA)
sites characteristic of mammalian FMOs, a `FATGY' motif that has also been
observed in a range of siderphore biosynthetic enzymes [10], and a C-terminal
hydrophobic segment that is believed to anchor the monooxygenase to the
microsomal membrane [11].
 
FMOXYGENASE4 is a 10-element fingerprint that provides a signature for type
4 flavin-containing monooxygenases. The fingerprint was derived from an
initial alignment of 2 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise type 4 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. 
Summary Information
2 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 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
102222222222
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
20000000000
12345678910
True Positives
FMO4_HUMAN    FMO4_RABIT    
Sequence Titles
FMO4_HUMAN  DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 4 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 4) (FMO 4) (DIMETHYLANILINE OXIDASE 4) - HOMO SAPIENS (HUMAN). 
FMO4_RABIT DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 4 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 4) (FMO 4) (DIMETHYLANILINE OXIDASE 4) (FMO 1E1) - ORYCTOLAGUS CUNICULUS (RABBIT).
Scan History
SPTR37_9f  1  50   NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
KFTESSKDGMTRVY FMO4_HUMAN 41 41 -
KYTETSKDGMTRIY FMO4_RABIT 41 41 -

Motif 2 width=13
Element Seqn Id St Int Rpt
FMNHEKFWDYLQE FMO4_HUMAN 80 25 -
FMSHSKFWNYLQE FMO4_RABIT 80 25 -

Motif 3 width=10
Element Seqn Id St Int Rpt
QILHSQEYKI FMO4_HUMAN 168 75 -
QILHCQEYKI FMO4_RABIT 168 75 -

Motif 4 width=15
Element Seqn Id St Int Rpt
YNMMVTRRCCSFIAQ FMO4_HUMAN 230 52 -
FNMMITRRCLNVIEQ FMO4_RABIT 230 52 -

Motif 5 width=13
Element Seqn Id St Int Rpt
LSITKGKKAKFIV FMO4_HUMAN 270 25 -
LSITKGKNPKFIV FMO4_RABIT 270 25 -

Motif 6 width=13
Element Seqn Id St Int Rpt
PLKSLCTKKIFLY FMO4_HUMAN 339 56 -
PLRSLCMKKMFLY FMO4_RABIT 339 56 -

Motif 7 width=13
Element Seqn Id St Int Rpt
GVFKDTSKDKFDY FMO4_HUMAN 417 65 -
GVIKDTSEEKLSY FMO4_RABIT 417 65 -

Motif 8 width=18
Element Seqn Id St Int Rpt
DSSKPASMSHYLKAWGAP FMO4_HUMAN 503 73 -
DSSKSASLSHYLKVWGAP FMO4_RABIT 504 74 -

Motif 9 width=16
Element Seqn Id St Int Rpt
PVLLASLLLICKSSLF FMO4_HUMAN 520 -1 -
PLLLASVLLICKSSHF FMO4_RABIT 521 -1 -

Motif 10 width=18
Element Seqn Id St Int Rpt
FLKLVRDKLQDRMSPYLV FMO4_HUMAN 535 -1 -
FLKSVRDKLQNRIFPYLV FMO4_RABIT 536 -1 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
KFTESSKDGMTRVY FMO4_HUMAN 41 41 -
KYTETSKDGMTRIY FMO4_RABIT 41 41 -

Motif 2 width=13
Element Seqn Id St Int Rpt
FMNHEKFWDYLQE FMO4_HUMAN 80 25 -
FMSHSKFWNYLQE FMO4_RABIT 80 25 -

Motif 3 width=10
Element Seqn Id St Int Rpt
QILHSQEYKI FMO4_HUMAN 168 75 -
QILHCQEYKI FMO4_RABIT 168 75 -

Motif 4 width=15
Element Seqn Id St Int Rpt
YNMMVTRRCCSFIAQ FMO4_HUMAN 230 52 -
FNMMITRRCLNVIEQ FMO4_RABIT 230 52 -

Motif 5 width=13
Element Seqn Id St Int Rpt
LSITKGKKAKFIV FMO4_HUMAN 270 25 -
LSITKGKNPKFIV FMO4_RABIT 270 25 -

Motif 6 width=13
Element Seqn Id St Int Rpt
PLKSLCTKKIFLY FMO4_HUMAN 339 56 -
PLRSLCMKKMFLY FMO4_RABIT 339 56 -

Motif 7 width=13
Element Seqn Id St Int Rpt
GVFKDTSKDKFDY FMO4_HUMAN 417 65 -
GVIKDTSEEKLSY FMO4_RABIT 417 65 -

Motif 8 width=18
Element Seqn Id St Int Rpt
DSSKPASMSHYLKAWGAP FMO4_HUMAN 503 73 -
DSSKSASLSHYLKVWGAP FMO4_RABIT 504 74 -

Motif 9 width=16
Element Seqn Id St Int Rpt
PVLLASLLLICKSSLF FMO4_HUMAN 520 -1 -
PLLLASVLLICKSSHF FMO4_RABIT 521 -1 -

Motif 10 width=18
Element Seqn Id St Int Rpt
FLKLVRDKLQDRMSPYLV FMO4_HUMAN 535 -1 -
FLKSVRDKLQNRIFPYLV FMO4_RABIT 536 -1 -