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PR01121

Identifier
FMOXYGENASE1  [View Relations]  [View Alignment]  
Accession
PR01121
No. of Motifs
10
Creation Date
29-APR-1999
Title
Flavin-containing monooxygenase (FMO) 1 signature
Database References
PRINTS; PR00370 FMOXYGENASE
PFAM; PF00743 FMO-like
INTERPRO; IPR002253
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. 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).
 
9. 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.
 
Human FMO1 mRNA is more abundant in foetal than in adult liver, indicating 
that the enzyme is subject to developmental regulation in man [2]. Southern
blot hybridisation of human genomic DNA suggests that the protein is encoded 
by a single gene that maps to chromosome 1. The deduced 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 [8], and a C-terminal hydrophobic segment that is believed to anchor
the monooxygenase to the microsomal membrane [9]. The human sequence shares 
88 and 86% identity, respectively, with pig and rabbit "hepatic" forms of
FMO, but is only 58% similar to the rabbit "pulmonary" FMO [2].
 
FMOXYGENASE1 is a 10-element fingerprint that provides a signature for type
1 flavin-containing monooxygenases. The fingerprint was derived from an
initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise type 1 FMOs but distinguish them from the rest
of the FMO family - motif 10 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, murine type 5 FMO (FMO5_MOUSE), which 
matches motifs 1 and 2.
Summary Information
   5 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
1 codes involving 2 elements
Composite Feature Index
105555555555
90000000000
80000000000
70000000000
60000000000
50000000000
40000000000
30000000000
21100000000
12345678910
True Positives
FMO1_HUMAN    FMO1_MOUSE    FMO1_PIG      FMO1_RABIT    
FMO1_RAT
True Positive Partials
Codes involving 2 elements
FMO5_MOUSE
Sequence Titles
FMO1_HUMAN  DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 1 (EC 1.14.13.8) (FETAL HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 1) (FMO 1) (DIMETHYLANILINE OXIDASE 1) - HOMO SAPIENS (HUMAN). 
FMO1_MOUSE DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 1 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 1) (FMO 1) (DIMETHYLANILINE OXIDASE 1) - MUS MUSCULUS (MOUSE).
FMO1_PIG DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 1 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 1) (FMO 1) (DIMETHYLANILINE OXIDASE 1) - SUS SCROFA (PIG).
FMO1_RABIT DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 1 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 1) (FMO 1) (DIMETHYLANILINE OXIDASE 1) (FMO 1A1) (FMO FORM 1) - ORYCTOLAGUS CUNICULUS (RABBIT).
FMO1_RAT DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 1 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 1) (FMO 1) (DIMETHYLANILINE OXIDASE 1) - RATTUS NORVEGICUS (RAT).

FMO5_MOUSE DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 5 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 5) (FMO 5) (DIMETHYLANILINE OXIDASE 5) - MUS MUSCULUS (MOUSE).
Scan History
SPTR37_9f  1  7    NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
VPNSLFLEYLKLYSTQF FMO1_MOUSE 82 82 -
VPNSLFLEYLQLYATQF FMO1_RAT 82 82 -
VPNSHFLEYLRMYANQF FMO1_PIG 81 81 -
VPNSQFLDYLKMYADRF FMO1_RABIT 81 81 -
VPNSQFLEYLKMYANHF FMO1_HUMAN 81 81 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LAKKVFLSTTGGA FMO1_MOUSE 206 107 -
LAKKVFLSTTGGA FMO1_RAT 206 107 -
LAKKVFLSTTGGA FMO1_PIG 205 107 -
VAKKVFLSTTGGA FMO1_RABIT 205 107 -
LAEKVFLSTTGGG FMO1_HUMAN 205 107 -

Motif 3 width=15
Element Seqn Id St Int Rpt
TPIVSWLISKKMNSW FMO1_MOUSE 249 30 -
TPVVSWLISKKMNSW FMO1_RAT 249 30 -
TPIVNWLIAKKMNSW FMO1_PIG 248 30 -
TPIVTWLVAKKMNSW FMO1_RABIT 248 30 -
TPIVTWLMERKINNW FMO1_HUMAN 248 30 -

Motif 4 width=14
Element Seqn Id St Int Rpt
GRIITGKVFIKPSI FMO1_MOUSE 290 26 -
GRIITGKVLIKPSI FMO1_RAT 290 26 -
GRIITGKVLIKPSI FMO1_PIG 289 26 -
GRIITGKVFIRPSI FMO1_RABIT 289 26 -
GRIITGKVFIRPSI FMO1_HUMAN 289 26 -

Motif 5 width=10
Element Seqn Id St Int Rpt
NNTPKEEPID FMO1_MOUSE 314 10 -
NNTPKEEPID FMO1_RAT 314 10 -
NSSPEEEPID FMO1_PIG 313 10 -
HNTPSEEPID FMO1_RABIT 316 13 -
NNTSKEEPID FMO1_HUMAN 313 10 -

Motif 6 width=11
Element Seqn Id St Int Rpt
VVKVEDGQASL FMO1_MOUSE 342 18 -
IVKVEDGQASL FMO1_RAT 342 18 -
VVKVEDGQASL FMO1_PIG 341 18 -
VVKVEDGQASL FMO1_RABIT 344 18 -
VVKVEDGQASL FMO1_HUMAN 341 18 -

Motif 7 width=10
Element Seqn Id St Int Rpt
GATTLPPPSV FMO1_MOUSE 395 42 -
GATTLPPPSV FMO1_RAT 395 42 -
GVNKLPPSSV FMO1_PIG 394 42 -
GVIKLPPTSV FMO1_RABIT 397 42 -
GVNKLPPPSV FMO1_HUMAN 394 42 -

Motif 8 width=20
Element Seqn Id St Int Rpt
NERKKNKHSGFGLCYCKALQ FMO1_MOUSE 410 5 -
NERKKNKHSGFGLCYCKALQ FMO1_RAT 410 5 -
NTRKENKPSGFGLCYCKALQ FMO1_PIG 409 5 -
NERKENKHNGFGLCYCKALQ FMO1_RABIT 412 5 -
NARKENKPSWFGLCYCKALQ FMO1_HUMAN 409 5 -

Motif 9 width=17
Element Seqn Id St Int Rpt
TVKVTKTRTIQESPSSF FMO1_MOUSE 495 65 -
TVNVTKTRTVQETPSTF FMO1_RAT 495 65 -
TFKVTKTRIVKESPSPF FMO1_PIG 494 65 -
TFKVTKTRIVQESSSPF FMO1_RABIT 497 65 -
TFKVIKARVVQESPSPF FMO1_HUMAN 494 65 -

Motif 10 width=21
Element Seqn Id St Int Rpt
FETLLKLFSFLALLIAVFLIF FMO1_MOUSE 511 -1 -
FETLLKLFSFLALLVAVFFIF FMO1_RAT 511 -1 -
FASLLKLFSFLALLVAIFQIF FMO1_PIG 510 -1 -
FESLLKLFAVLALLVSVFLIF FMO1_RABIT 513 -1 -
FESFLKVFSFLALLVAIFLIF FMO1_HUMAN 510 -1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
VPNSLFLEYLKLYSTQF FMO1_MOUSE 82 82 -
VPNSLFLEYLQLYATQF FMO1_RAT 82 82 -
VPNSHFLEYLRMYANQF FMO1_PIG 81 81 -
VPNSQFLDYLKMYADRF FMO1_RABIT 81 81 -
VPNSQFLEYLKMYANHF FMO1_HUMAN 81 81 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LAKKVFLSTTGGA FMO1_MOUSE 206 107 -
LAKKVFLSTTGGA FMO1_RAT 206 107 -
LAKKVFLSTTGGA FMO1_PIG 205 107 -
VAKKVFLSTTGGA FMO1_RABIT 205 107 -
LAEKVFLSTTGGG FMO1_HUMAN 205 107 -

Motif 3 width=15
Element Seqn Id St Int Rpt
TPIVSWLISKKMNSW FMO1_MOUSE 249 30 -
TPVVSWLISKKMNSW FMO1_RAT 249 30 -
TPIVNWLIAKKMNSW FMO1_PIG 248 30 -
TPIVTWLVAKKMNSW FMO1_RABIT 248 30 -
TPIVTWLMERKINNW FMO1_HUMAN 248 30 -

Motif 4 width=14
Element Seqn Id St Int Rpt
GRIITGKVFIKPSI FMO1_MOUSE 290 26 -
GRIITGKVLIKPSI FMO1_RAT 290 26 -
GRIITGKVLIKPSI FMO1_PIG 289 26 -
GRIITGKVFIRPSI FMO1_RABIT 289 26 -
GRIITGKVFIRPSI FMO1_HUMAN 289 26 -

Motif 5 width=10
Element Seqn Id St Int Rpt
NNTPKEEPID FMO1_MOUSE 314 10 -
NNTPKEEPID FMO1_RAT 314 10 -
NSSPEEEPID FMO1_PIG 313 10 -
HNTPSEEPID FMO1_RABIT 316 13 -
NNTSKEEPID FMO1_HUMAN 313 10 -

Motif 6 width=11
Element Seqn Id St Int Rpt
VVKVEDGQASL FMO1_MOUSE 342 18 -
IVKVEDGQASL FMO1_RAT 342 18 -
VVKVEDGQASL FMO1_PIG 341 18 -
VVKVEDGQASL FMO1_RABIT 344 18 -
VVKVEDGQASL FMO1_HUMAN 341 18 -

Motif 7 width=10
Element Seqn Id St Int Rpt
GATTLPPPSV FMO1_MOUSE 395 42 -
GATTLPPPSV FMO1_RAT 395 42 -
GVNKLPPSSV FMO1_PIG 394 42 -
GVIKLPPTSV FMO1_RABIT 397 42 -
GVNKLPPPSV FMO1_HUMAN 394 42 -

Motif 8 width=20
Element Seqn Id St Int Rpt
NERKKNKHSGFGLCYCKALQ FMO1_MOUSE 410 5 -
NERKKNKHSGFGLCYCKALQ FMO1_RAT 410 5 -
NTRKENKPSGFGLCYCKALQ FMO1_PIG 409 5 -
NERKENKHNGFGLCYCKALQ FMO1_RABIT 412 5 -
NARKENKPSWFGLCYCKALQ FMO1_HUMAN 409 5 -

Motif 9 width=17
Element Seqn Id St Int Rpt
TVKVTKTRTIQESPSSF FMO1_MOUSE 495 65 -
TVNVTKTRTVQETPSTF FMO1_RAT 495 65 -
TFKVTKTRIVKESPSPF FMO1_PIG 494 65 -
TFKVTKTRIVQESSSPF FMO1_RABIT 497 65 -
TFKVIKARVVQESPSPF FMO1_HUMAN 494 65 -

Motif 10 width=21
Element Seqn Id St Int Rpt
FETLLKLFSFLALLIAVFLIF FMO1_MOUSE 511 -1 -
FETLLKLFSFLALLVAVFFIF FMO1_RAT 511 -1 -
FASLLKLFSFLALLVAIFQIF FMO1_PIG 510 -1 -
FESLLKLFAVLALLVSVFLIF FMO1_RABIT 513 -1 -
FESFLKVFSFLALLVAIFLIF FMO1_HUMAN 510 -1 -