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PR01125

Identifier
FMOXYGENASE5  [View Relations]  [View Alignment]  
Accession
PR01125
No. of Motifs
9
Creation Date
29-APR-1999
Title
Flavin-containing monooxygenase (FMO) 5 signature
Database References
PRINTS; PR00370 FMOXYGENASE
PFAM; PF00743 FMO-like
INTERPRO; IPR002257
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. CHERRINGTON, N.J., FALLS, J.G., ROSE, R.L., CLEMENTS, K.M.,
PHILPOT, R.M., LEVI, P.E. AND HODGSON, E.
Molecular cloning, sequence, and expression of mouse flavin-containing
monooxygenases 1 and 5 (FMO1 and FMO5)
J.BIOCHEM.MOL.TOXICOL. 12 205-212(1998). 
 
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. OVERBY, L.H., BUCKPITT, A.R., LAWTON, M.P., ATTA-ASAFO-ADJEI, E.,
SCHULZE, J. AND PHILPOT, R.M.
Characterization of flavin-containing monooxygenase 5 (FMO5) cloned from
human and guinea pig: evidence that the unique catalytic properties of FMO5
are not confined to the rabbit ortholog.
ARCH.BIOCHEM.BIOPHYS. 317 275-284 (1995). 

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.
 
The deduced amino acid sequence of human FM05 includes the putative FAD- 
(GxGxxG) and NADP+ pyrophosphate-binding (GxGxxA) sites characteristic of 
mammalian FMOs [8], 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].
 
Human and guinea pig FMO5, like other FMOs, are encoded by multiple
transcripts. FMO5 has been identified in livers of adult humans, rabbits
and guinea pigs, and foetal livers of humans [11]. Neither the human nor 
guinea pig enzyme effectively catalyse the metabolism of methimazole, a
general FMO substrate; however, both are active with n-octylamine [11]. The
responses to detergent, ions and elevated temperature are all similar to 
those observed in rabbit FMO5, suggesting that these properties are species-
independent and that this form of FMO is not readily classified as a drug-
metabolising enzyme [11]. 
 
FMOXYGENASE5 is a 9-element fingerprint that provides a signature for type
5 flavin-containing monooxygenases. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise type 5 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
4 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
9444444444
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
FMO5_CAVPO    FMO5_HUMAN    FMO5_MOUSE    FMO5_RABIT    
Sequence Titles
FMO5_CAVPO  DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 5 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 5) (FMO 5) (DIMETHYLANILINE OXIDASE 5) - CAVIA PORCELLUS (GUINEA PIG). 
FMO5_HUMAN DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 5 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 5) (FMO 5) (DIMETHYLANILINE OXIDASE 5) - HOMO SAPIENS (HUMAN).
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).
FMO5_RABIT DIMETHYLANILINE MONOOXYGENASE [N-OXIDE FORMING] 5 (EC 1.14.13.8) (HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 5) (FMO 5) (DIMETHYLANILINE OXIDASE 5) (FMO 1C1) (FMO FORM 3) - ORYCTOLAGUS CUNICULUS (RABBIT).
Scan History
SPTR37_9f  2  6    NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
VLEYFRMYAKEFD FMO5_HUMAN 87 87 -
VLEYFRMYAKEFG FMO5_CAVPO 87 87 -
VLEYFRMYAKEFD FMO5_MOUSE 87 87 -
VLEYFRMYAKEFG FMO5_RABIT 87 87 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TAKQVFLSTRR FMO5_HUMAN 206 106 -
TAKQVFLSTRR FMO5_CAVPO 206 106 -
TAKQVFLSTRR FMO5_MOUSE 206 106 -
TAKQVFLSTRR FMO5_RABIT 206 106 -

Motif 3 width=20
Element Seqn Id St Int Rpt
SSRLTHFIWKICGQSLANKY FMO5_HUMAN 236 19 -
SSRFTYFLSKILGQSLSNAY FMO5_CAVPO 236 19 -
SSRIMYYLSRICGPSLKNNY FMO5_MOUSE 236 19 -
SSRFSQFLKKITGETIANSF FMO5_RABIT 236 19 -

Motif 4 width=12
Element Seqn Id St Int Rpt
KHRALSQHPTLN FMO5_HUMAN 274 18 -
KHRAMSQHPTVN FMO5_CAVPO 274 18 -
KHRALSQHPTVN FMO5_MOUSE 274 18 -
KHRALSQHPTVN FMO5_RABIT 274 18 -

Motif 5 width=9
Element Seqn Id St Int Rpt
KVVKNKISL FMO5_HUMAN 343 57 -
KVVKNKVSL FMO5_CAVPO 343 57 -
KVVKNKVSL FMO5_MOUSE 343 57 -
KVVKNKVSL FMO5_RABIT 343 57 -

Motif 6 width=20
Element Seqn Id St Int Rpt
SQSEMMAEISKAQEEIDKRY FMO5_HUMAN 400 48 -
SQSEMMAEITKAQEEIAKRY FMO5_CAVPO 400 48 -
SQSEMMAEINKAREEMAKRY FMO5_MOUSE 400 48 -
SQSEMMTEISQVQEKMAKRY FMO5_RABIT 400 48 -

Motif 7 width=12
Element Seqn Id St Int Rpt
YVESQRHTIQGD FMO5_HUMAN 419 -1 -
YVDSQRHTIQGD FMO5_CAVPO 419 -1 -
YVDSQRHTIQGD FMO5_MOUSE 419 -1 -
YVESQRHTIQGD FMO5_RABIT 419 -1 -

Motif 8 width=15
Element Seqn Id St Int Rpt
TRVVERSSSMTSTMT FMO5_HUMAN 500 69 -
TRETEKSNSMVSAVT FMO5_CAVPO 500 69 -
TRVVERDSSGGSLVT FMO5_MOUSE 500 69 -
TRVTESSNSVTSMMT FMO5_RABIT 500 69 -

Motif 9 width=18
Element Seqn Id St Int Rpt
TIGKFMLALAFFAIIIAY FMO5_HUMAN 514 -1 -
TTGCFMLAVVFFAIIMAY FMO5_CAVPO 514 -1 -
TVRVLMLAVAFFAVILAY FMO5_MOUSE 514 -1 -
TMGKFMLAIAFLAIAVVY FMO5_RABIT 514 -1 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
VLEYFRMYAKEFD FMO5_HUMAN 87 87 -
VLEYFRMYAKEFG FMO5_CAVPO 87 87 -
VLEYFRMYAKEFD FMO5_MOUSE 87 87 -
VLEYFRMYAKEFG FMO5_RABIT 87 87 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TAKQVFLSTRR FMO5_HUMAN 206 106 -
TAKQVFLSTRR FMO5_CAVPO 206 106 -
TAKQVFLSTRR FMO5_MOUSE 206 106 -
TAKQVFLSTRR FMO5_RABIT 206 106 -

Motif 3 width=20
Element Seqn Id St Int Rpt
SSRLTHFIWKICGQSLANKY FMO5_HUMAN 236 19 -
SSRFTYFLSKILGQSLSNAY FMO5_CAVPO 236 19 -
SSRIMYYLSRICGPSLKNNY FMO5_MOUSE 236 19 -
SSRFSQFLKKITGETIANSF FMO5_RABIT 236 19 -

Motif 4 width=12
Element Seqn Id St Int Rpt
KHRALSQHPTLN FMO5_HUMAN 274 18 -
KHRAMSQHPTVN FMO5_CAVPO 274 18 -
KHRALSQHPTVN FMO5_MOUSE 274 18 -
KHRALSQHPTVN FMO5_RABIT 274 18 -

Motif 5 width=9
Element Seqn Id St Int Rpt
KVVKNKISL FMO5_HUMAN 343 57 -
KVVKNKVSL FMO5_CAVPO 343 57 -
KVVKNKVSL FMO5_MOUSE 343 57 -
KVVKNKVSL FMO5_RABIT 343 57 -

Motif 6 width=20
Element Seqn Id St Int Rpt
SQSEMMAEISKAQEEIDKRY FMO5_HUMAN 400 48 -
SQSEMMAEITKAQEEIAKRY FMO5_CAVPO 400 48 -
SQSEMMAEINKAREEMAKRY FMO5_MOUSE 400 48 -
SQSEMMTEISQVQEKMAKRY FMO5_RABIT 400 48 -

Motif 7 width=12
Element Seqn Id St Int Rpt
YVESQRHTIQGD FMO5_HUMAN 419 -1 -
YVDSQRHTIQGD FMO5_CAVPO 419 -1 -
YVDSQRHTIQGD FMO5_MOUSE 419 -1 -
YVESQRHTIQGD FMO5_RABIT 419 -1 -

Motif 8 width=15
Element Seqn Id St Int Rpt
TRVVERSSSMTSTMT FMO5_HUMAN 500 69 -
TRETEKSNSMVSAVT FMO5_CAVPO 500 69 -
TRVVERDSSGGSLVT FMO5_MOUSE 500 69 -
TRVTESSNSVTSMMT FMO5_RABIT 500 69 -

Motif 9 width=18
Element Seqn Id St Int Rpt
TIGKFMLALAFFAIIIAY FMO5_HUMAN 514 -1 -
TTGCFMLAVVFFAIIMAY FMO5_CAVPO 514 -1 -
TVRVLMLAVAFFAVILAY FMO5_MOUSE 514 -1 -
TMGKFMLAIAFLAIAVVY FMO5_RABIT 514 -1 -