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PR01763

Identifier
DISHEVELLED3  [View Relations]  [View Alignment]  
Accession
PR01763
No. of Motifs
4
Creation Date
01-AUG-2002
Title
Dishevelled-3 protein signature
Database References
PRINTS; PR01760 DISHEVELLED
MIM; 601368
Literature References
1. WODARZ, A. AND NUSSE, R.
Mechanisms of Wnt signal transduction.
ANNU.REV.CELL DEV.BIOL. 14 59-88 (1998).
 
2. BEJSOVEC, A.
Signal transduction: Wnt signalling shows its versatility.
CURR.BIOL. 9 R684-R687 (1999).
 
3. DE FERRARI, G.V. AND INESTROSA, N.C.
Wnt signaling function in Alzheimer's disease.
BRAIN RES.BRAIN RES.REV. 33 1-12 (2000).
 
4. SEMENOV, M.V. AND SNYDER, M.
Human dishevelled genes constitute a DHR-containing multigene family.
GENOMICS 42 302-310 (1997).
 
5. PEIFER, M. AND POLAKIS, P.
Wnt signalling in oncogenesis and embryogenesis - a look outside the
nucleus.
SCIENCE 287 1606-1609 (2000).
 
6. MOON, R.T.
An introduction to non-canonical Wnt and Frizzled signaling.
SEMIN.CELL DEV.BIOL. 13 215 (2002).
 
7. PENTON, A., WODARZ, A. AND NUSSE, R.
A mutational analysis of dishevelled in Drosophila defines novel domains in
the dishevelled protein as well as novel suppressing alleles of axin.
GENETICS 161 747-762 (2002).
 
8. LEE, J.S., ISHIMOTO, A. AND YANAGAWA, S.
Characterization of mouse dishevelled (Dvl) proteins in Wnt/wingless
signaling pathway.
J.BIOL.CHEM. 274 21464-21470 (1999).
 
9. TSANG, M., LIJAM, N., YANG, Y., BEIER D.R., WYNSHAW-BORIS, A. AND 
SUSSMAN, D.J.
Isolation and characterization of mouse dishevelled-3.
DEV.DYN. 207 253-262 (1996).

Documentation
Wnt proteins constitute a large family of secreted signalling molecules that
are involved in intercellular signalling during development. The name 
derives from the first 2 members of the family to be discovered: int-1 
(mouse) and wingless (Wg) (Drosophila) [1]. It is now recognised that Wnt 
signalling controls many cell fate decisions in a variety of different 
organisms, including mammals [2]. Wnt signalling has been implicated in 
tumorigenesis, early mesodermal patterning of the embryo, morphogenesis of 
the brain and kidneys, regulation of mammary gland proliferation and 
Alzheimer's disease [3,4].
 
Wnt signal transduction proceeds initially via binding to their cell
surface receptors - the so-called frizzled proteins. This activates the
signalling functions of B-catenin and regulates the expression of specific
genes important in development [5]. More recently, however, several non-
canonical Wnt signalling pathways have been elucidated that act
independently of B-catenin [6]. In both cases, the transduction mechanism
requires dishevelled protein (Dsh), a cytoplasmic phosphoprotein that acts
directly downstream of frizzled [7]. In addition to its role in Wnt
signalling, Dsh is also involved in generating planar polarity in Drosophila
and has been implicated in the Notch signal transduction cascade. Three 
human and mouse homologues of Dsh have been cloned (DVL-1 to 3); it is 
believed that these proteins, like their Drosophila counterpart, are 
involved in signal transduction. Human and murine orthologues share more 
than 95% sequence identity and are each 40-50% identical to Drosophila Dsh.
 
Sequence similarity amongst Dsh proteins is concentrated around three 
conserved domains: at the N-terminus lies a DIX domain (mutations 
mapping to this region reduce or completely disrupt Wg signalling); a PDZ 
(or DHR) domain, often found in proteins involved in protein-protein 
interactions, lies within the central portion of the protein (point 
mutations within this module have been shown to have little effect on 
Wg-mediated signal transduction); and a DEP domain is located towards the C-
terminus and is conserved among a set of proteins that regulate various 
GTPases (whilst genetic and molecular assays have shown this module to be 
dispensible for Wg signalling, it is thought to be important in planar 
polarity signalling in flies [7,8]).
 
Mouse DVL-3 was first cloned in 1996 [9], followed by the human orthologue 
in 1997 [4]. Both the human and murine genes encode polypeptides of 716 
amino acids. In adult mice, DVL-3 expression is widespread, with highest 
levels exhibited in brain, ovary and heart. It is expressed ubiquitously in
the early embryo and, by 10.5 days post-coitum, is most abundantly expressed
in tissues of the dorsal root ganglia, somites, limb buds, branchial arches, 
heart, gut and throughout the developing central nervous system [8]. 
 
DISHEVELLED3 is a 4-element fingerprint that provides a signature for 
dishevelled-3 (DVL-3) proteins. The fingerprint was derived from an initial 
alignment of 3 sequences: the motifs were drawn from conserved regions 
spanning the C-terminal portion of the alignment, focusing on those sections 
that characterise DVL-3 proteins but distinguish them from closely related 
members of the Dsh family - motifs 1-4 reside in the C-terminal region 
beyond the putative DEP domain. A single iteration on SPTR40_20f was 
required to reach convergence, no further sequences being identified beyond 
the starting set.
Summary Information
3 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
43333
30000
20000
1234
True Positives
DVL3_HUMAN    DVL3_MOUSE    Q9UG07        
Sequence Titles
DVL3_HUMAN  Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) - Homo sapiens (Human). 
DVL3_MOUSE Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) - Mus musculus (Mouse).
Q9UG07 HYPOTHETICAL 59.3 KDA PROTEIN - Homo sapiens (Human).
Scan History
SPTR40_20f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
GNMANLSLHDH DVL3_HUMAN 499 499 -
GNMANLSLHDH Q9UG07 331 331 -
GNMANLSLHDH DVL3_MOUSE 499 499 -

Motif 2 width=10
Element Seqn Id St Int Rpt
PGFPELGYSY DVL3_HUMAN 551 41 -
PGFPELGYSY Q9UG07 383 41 -
PGFPELGYSY DVL3_MOUSE 551 41 -

Motif 3 width=12
Element Seqn Id St Int Rpt
RRKEKDPKAGDS DVL3_HUMAN 585 24 -
RRKEKDPKAGDS Q9UG07 417 24 -
RRKEKDPKAGDS DVL3_MOUSE 585 24 -

Motif 4 width=12
Element Seqn Id St Int Rpt
HRSHHSLASSLR DVL3_HUMAN 634 37 -
HRSHHSLASSLR Q9UG07 466 37 -
HRSHHSLTSSLR DVL3_MOUSE 634 37 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
GNMANLSLHDH DVL3_HUMAN 499 499 -
GNMANLSLHDH Q9UG07 331 331 -
GNMANLSLHDH DVL3_MOUSE 499 499 -

Motif 2 width=10
Element Seqn Id St Int Rpt
PGFPELGYSY DVL3_HUMAN 551 41 -
PGFPELGYSY Q9UG07 383 41 -
PGFPELGYSY DVL3_MOUSE 551 41 -

Motif 3 width=12
Element Seqn Id St Int Rpt
RRKEKDPKAGDS DVL3_HUMAN 585 24 -
RRKEKDPKAGDS Q9UG07 417 24 -
RRKEKDPKAGDS DVL3_MOUSE 585 24 -

Motif 4 width=12
Element Seqn Id St Int Rpt
HRSHHSLASSLR DVL3_HUMAN 634 37 -
HRSHHSLASSLR Q9UG07 466 37 -
HRSHHSLTSSLR DVL3_MOUSE 634 37 -