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PR01762

Identifier
DISHEVELLED2  [View Relations]  [View Alignment]  
Accession
PR01762
No. of Motifs
4
Creation Date
01-AUG-2002
Title
Dishevelled-2 protein signature
Database References
PRINTS; PR01760 DISHEVELLED
MIM; 602151
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. KLINGENSMITH, J., YANG, Y., AXELROD, J.D., BEIER, D.R., PERRIMON, N., AND
SUSSMAN, D.J.
Conservation of dishevelled structure and function between flies and mice: 
Isolation and characterization of Dvl2.
MECH.DEV. 58 15-26 (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-2 was first cloned in 1996 [9], followed by the human orthologue 
in 1997 [4]. Both the human and murine genes encode polypeptides of 736 
amino acids, the human protein sharing 73% identity with Xenopus Dsh.
Immunoblotting analysis of human DVL-2 in human embryonic tissues showed
the protein to be abundantly expressed in the lung, less prevalent in the 
kidney, and present at very low level in thymus, liver and intestinal 
tissues [4]. 
 
DISHEVELLED2 is a 4-element fingerprint that provides a signature for 
dishevelled-2 (DVL-2) proteins. The fingerprint was derived from an initial 
alignment of 3 sequences: the motifs were drawn from conserved regions 
spanning the full alignment length, focusing on those sections that 
characterise DVL-2 proteins but distinguish them from closely related 
members of the Dsh family - motif 1 lies at the N-terminus, within the 
putative DIX domain; motif 2 includes part of the C-terminal portion of the 
putative DEP domain; and motifs 3 and 4 reside at the C-terminus. 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
DVL2_HUMAN    DVL2_MOUSE    DVL2_XENLA    
Sequence Titles
DVL2_HUMAN  Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) - Homo sapiens (Human). 
DVL2_MOUSE Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) - Mus musculus (Mouse).
DVL2_XENLA Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) (Xdsh) - Xenopus laevis (African clawed frog).
Scan History
SPTR40_20f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
QPEVAPPAHESR DVL2_MOUSE 96 96 -
QPEMAPPVHEPR DVL2_HUMAN 96 96 -
QPDSAPPAPATE DVL2_XENLA 85 85 -

Motif 2 width=11
Element Seqn Id St Int Rpt
GCESYLVNLSL DVL2_MOUSE 511 403 -
GCESYLVNLSL DVL2_HUMAN 511 403 -
GCENYMTNLSL DVL2_XENLA 505 408 -

Motif 3 width=10
Element Seqn Id St Int Rpt
SLRRGGEPGG DVL2_MOUSE 630 108 -
SLRRGGEASG DVL2_HUMAN 630 108 -
IRRVGGGEAG DVL2_XENLA 631 115 -

Motif 4 width=22
Element Seqn Id St Int Rpt
PSRGSTGAPPNLRALPGLHPYG DVL2_MOUSE 647 7 -
PSRGSTGGAPNLRAHPGLHPYG DVL2_HUMAN 647 7 -
PSERSTSSRLPPHHPPSVHSYA DVL2_XENLA 642 1 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
QPEVAPPAHESR DVL2_MOUSE 96 96 -
QPEMAPPVHEPR DVL2_HUMAN 96 96 -
QPDSAPPAPATE DVL2_XENLA 85 85 -

Motif 2 width=11
Element Seqn Id St Int Rpt
GCESYLVNLSL DVL2_MOUSE 511 403 -
GCESYLVNLSL DVL2_HUMAN 511 403 -
GCENYMTNLSL DVL2_XENLA 505 408 -

Motif 3 width=10
Element Seqn Id St Int Rpt
SLRRGGEPGG DVL2_MOUSE 630 108 -
SLRRGGEASG DVL2_HUMAN 630 108 -
IRRVGGGEAG DVL2_XENLA 631 115 -

Motif 4 width=22
Element Seqn Id St Int Rpt
PSRGSTGAPPNLRALPGLHPYG DVL2_MOUSE 647 7 -
PSRGSTGGAPNLRAHPGLHPYG DVL2_HUMAN 647 7 -
PSERSTSSRLPPHHPPSVHSYA DVL2_XENLA 642 1 -