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PR01574

Identifier
TUBBYPROTEIN  [View Relations]  [View Alignment]  
Accession
PR01574
No. of Motifs
9
Creation Date
19-AUG-2001
Title
Tubby protein signature
Database References
PRINTS; PR01573 SUPERTUBBY
PROSITE; PS01200 TUB_1; PS01201 TUB_2
BLOCKS; BL01200
MIM; 602280; 600132; 601197; 602309
Literature References
1. KLEYN, P.W., FAN, W., KOVATS, S.G., LEE, J.L., PULIDO, J.C., WU, Y., 
BERKEMEIER, L.R., MISUMI, D.J., HOLMGREN, L., CHARLAT, O., WOOLF, E.A., 
TAYBER, O., BRODY, T., SHU, P., HAWKINS, F., KENNEDY, B., BALDINI, L., 
EBELING, C., ALPERIN, G.D., DEEDS, J., LAKEY, N.D., CULPEPPER, J., CHEN, 
H., GLUECKSMANN-KUIS, M.A., CARLSON, G.A., DUYK, G.M. AND MOORE, K.J. 
Identification and characterization of the mouse obesity gene tubby: a 
member of a novel gene family. 
CELL 85 281-290 (1996). 
 
2. NOBEN-TRAUTH, K., NAGGERT, J.K., NORTH, M.A. AND NISHINA, P.M.
A candidate gene for the mouse mutation tubby.
NATURE 380 534-538 (1996). 
 
3. BOGGON, T.J., SHAN, W.S., SANTAGATA, S., MYERS, S.C. AND SHAPIRO, L. 
Implication of tubby proteins as transcription factors by structure- based 
functional analysis. 
SCIENCE 286 2119-2125 (1999).  

Documentation
A mutation in the mouse tub gene causes maturity-onset obesity, insulin 
resistance and sensory deficits [1,2]. By contrast with the rapid juvenile-
onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in
tubby mice develops gradually, and strongly resembles the late-onset obesity
observed in the human population [2]. Excessive deposition of adipose tissue
culminates in a two-fold increase of body weight. Tubby mice also suffer
retinal degeneration and neurosensory hearing loss [2]. The tripartite
character of the tubby phenotype is highly similar to human obesity
syndromes, such as Alstrom and Bardet-Biedl [2]. Although these phenotypes
indicate a vital role for tubby proteins, no biochemical function has yet
been ascribed to any family member [3], although it has been suggested that
the phenotypic features of tubby mice may be the result of cellular 
apoptosis triggered by expression of the mutuated tub gene [2].
 
Mammalian tub is a hydrophilic protein of ~500 residues. The N-terminal
portion of the protein is conserved neither in length nor sequence, but the 
C-terminal 250 residues are highly conserved. The C-terminal extremity
contains a cysteine residue that might play an important role in the normal
functioning of these proteins.
 
Tubby-like proteins (TULPs), which share the tub C-terminal domain, are 
found in a wide range of multicellular organisms [2]. The crystal structure
of the C-terminal core domain from mouse tubby has been determined to 1.9A
resolution [3], revealing an alpha-beta protein with a barrel architecture.
Structural analyses suggest that TULPs constitute a unique family of 
bipartite transcription factors [3]. 
 
TUBBYPROTEIN is a 9-element fingerprint that provides a signature for the
mammalian tubby protein. The fingerprint was derived from an initial
alignment of 2 sequences: the motifs were drawn from conserved regions
spanning the N-terminal half of the alignment. Two iterations on 
SPTR39.22_17.3f were required to reach convergence, at which point a true
set comprising 3 sequences was identified. Several partial matches were
also found, all of which are tubby-like proteins that match motifs 2 and 3.
Summary Information
   3 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
3 codes involving 2 elements
Composite Feature Index<
9333333333
8000000000
7000000000