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PR01760

Identifier
DISHEVELLED  [View Relations]  [View Alignment]  
Accession
PR01760
No. of Motifs
4
Creation Date
20-SEP-2002
Title
Dishevelled protein signature
Database References
PRINTS; PR01761 DISHEVELLED1; PR01762 DISHEVELLED2; PR01763 DISHEVELLED3

PFAM; PF02377
INTERPRO; IPR003351
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).

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]).
 
DISHEVELLED is a 4-element fingerprint that provides a signature for Dsh 
proteins. The fingerprint was derived from an initial alignment of 9 
sequences: the motifs were drawn from conserved regions spanning central
and C-terminal portions of the alignment, focusing on those sections that 
characterise Dsh proteins but distinguish them from other sequences 
that contain the genetically-mobile PDZ domain - motif 1 encodes part of 
the C-terminal portion of the PDZ domain; motif 2 lies between the PDZ and 
DEP domains; and motifs 3 and 4 reside within the DEP domain. Four 
iterations on SPTR40_20f were required to reach convergence, at which point 
a true set comprising 17 sequences was identified.
Summary Information
17 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
417171717
30000
20000
1234
True Positives
DSH_DROME     DVL1_HUMAN    DVL1_MOUSE    DVL2_HUMAN    
DVL2_MOUSE DVL2_XENLA DVL3_HUMAN DVL3_MOUSE
DVLL_HUMAN Q18467 Q95ZX3 Q95ZX4
Q9DGC7 Q9GTJ8 Q9NL46 Q9UG07
Q9VYZ9
Sequence Titles
DSH_DROME   Segment polarity protein dishevelled - Drosophila melanogaster (Fruit fly). 
DVL1_HUMAN Segment polarity protein dishevelled homolog DVL-1 (Dishevelled-1) (DSH homolog 1) - Homo sapiens (Human).
DVL1_MOUSE Segment polarity protein dishevelled homolog DVL-1 (Dishevelled-1) (DSH homolog 1) - Mus musculus (Mouse).
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).
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).
DVLL_HUMAN Segment polarity protein dishevelled homolog DVL-1-like (Dishevelled- 1-like) (DSH homolog 1-like) - Homo sapiens (Human).
Q18467 HYPOTHETICAL 49.3 KDA PROTEIN - Caenorhabditis elegans.
Q95ZX3 HYPOTHETICAL PROTEIN C34F11.9A - Caenorhabditis elegans.
Q95ZX4 HYPOTHETICAL PROTEIN C34F11.9C - Caenorhabditis elegans.
Q9DGC7 ORF - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9GTJ8 DISHEVELLED - Hydra attenuata (Hydra) (Hydra vulgaris).
Q9NL46 DISHEVELLED HOMOLOG - Ciona intestinalis.
Q9UG07 HYPOTHETICAL 59.3 KDA PROTEIN - Homo sapiens (Human).
Q9VYZ9 DSH PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR40_20f 4  300  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
HKPGPITLTVAKCWD DVL3_MOUSE 324 324 -
HKPGPITLTVAKCWD DVL3_HUMAN 324 324 -
HKPGPIVLTVAKCWD DVL2_HUMAN 342 342 -
HKPGPIVLTVAKCWG DVL2_MOUSE 342 342 -
HKPGPIVLTVAKCWD DVL2_XENLA 329 329 -
SQTGPISLTVAKCWD DVL1_HUMAN 326 326 -
SQTGPISLTVAKCWD DVLL_HUMAN 326 326 -
SQTGPISLTVAKCWD DVL1_MOUSE 326 326 -
QKPGPIKLVVAKCWD DSH_DROME 327 327 -

Motif 2 width=13
Element Seqn Id St Int Rpt
PAAWVSHTAAMTG DVL3_MOUSE 358 19 -
PAAWVSHTAAMTG DVL3_HUMAN 358 19 -
PAAWVSHSAALTG DVL2_HUMAN 376 19 -
PAAWVSHSAALTG DVL2_MOUSE 376 19 -
PAAWVSHSAALSG DVL2_XENLA 363 19 -
PAAWLSHTAALTG DVL1_HUMAN 360 19 -
PAAWLSHTAALTG DVLL_HUMAN 360 19 -
PAAWLSHTAALTG DVL1_MOUSE 360 19 -
PGAWVAHTQALTS DSH_DROME 361 19 -

Motif 3 width=11
Element Seqn Id St Int Rpt
HNVEGFTERRE DVL3_MOUSE 453 82 -
HNVEGFTDRRE DVL3_HUMAN 453 82 -
HHVEGFPERRE DVL2_HUMAN 464 75 -
HHVEGFPERRE DVL2_MOUSE 464 75 -
HHVEGFQDRRE DVL2_XENLA 459 83 -
THVEGFKERRE DVL1_HUMAN 431 58 -
THVEGFKERRE DVLL_HUMAN 431 58 -
THVEGFKERRE DVL1_MOUSE 456 83 -
ENVEDVQDRRE DSH_DROME 435 61 -

Motif 4 width=12
Element Seqn Id St Int Rpt
HTVNKITFSEQC DVL3_MOUSE 479 15 -
HTVNKITFSEQC DVL3_HUMAN 479 15 -
HTVNKITFSEQC DVL2_HUMAN 490 15 -
HTVNKITFSEQC DVL2_MOUSE 490 15 -
HTVNKITFSEQC DVL2_XENLA 485 15 -
HTVNKITFSEQC DVL1_HUMAN 457 15 -
HTVNKITFSEQC DVLL_HUMAN 457 15 -
HTVNKITFSEQC DVL1_MOUSE 482 15 -
HTVNKLTFSEQC DSH_DROME 461 15 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
HKPGPITLTVAKCWD DVL3_MOUSE 324 324 -
HKPGPITLTVAKCWD DVL3_HUMAN 324 324 -
HKPGPITLTVAKCWD Q9UG07 156 156 -
HKPGPIVLTVAKCWD DVL2_HUMAN 342 342 -
HKPGPVSLTVAKCWD Q9DGC7 330 330 -
HKPGPIVLTVAKCWG DVL2_MOUSE 342 342 -
HKPGPIVLTVAKCWD DVL2_XENLA 329 329 -
SQTGPISLTVAKCWD DVL1_HUMAN 326 326 -
SQTGPISLTVAKCWD DVLL_HUMAN 326 326 -
SQTGPISLTVAKCWD DVL1_MOUSE 326 326 -
QKPGPIKLVVAKCWD DSH_DROME 327 327 -
QKPGPIKLVVAKCWD Q9VYZ9 327 327 -
HKPGPIMLTVAKCWD Q9GTJ8 299 299 -
HKPGPITLTVAKCWD Q9NL46 286 286 -
SRRGPIKLTVAKSFE Q18467 246 246 -
SRRGPIKLTVAKSFE Q95ZX3 378 378 -
SRRGPIKLTVAKSFE Q95ZX4 378 378 -

Motif 2 width=13
Element Seqn Id St Int Rpt
PAAWVSHTAAMTG DVL3_MOUSE 358 19 -
PAAWVSHTAAMTG DVL3_HUMAN 358 19 -
PAAWVSHTAAMTG Q9UG07 190 19 -
PAAWVSHSAALTG DVL2_HUMAN 376 19 -
PAAWVSHTAAMTG Q9DGC7 364 19 -
PAAWVSHSAALTG DVL2_MOUSE 376 19 -
PAAWVSHSAALSG DVL2_XENLA 363 19 -
PAAWLSHTAALTG DVL1_HUMAN 360 19 -
PAAWLSHTAALTG DVLL_HUMAN 360 19 -
PAAWLSHTAALTG DVL1_MOUSE 360 19 -
PGAWVAHTQALTS DSH_DROME 361 19 -
PGAWVAHTQALTS Q9VYZ9 361 19 -
PAAWMQHSEAVRA Q9GTJ8 333 19 -
PAAWANHIMTVKG Q9NL46 320 19 -
TQAWIQHTNAMRG Q18467 282 21 -
TQAWIQHTNAMRG Q95ZX3 414 21 -
TQAWIQHTNAMRG Q95ZX4 414 21 -

Motif 3 width=11
Element Seqn Id St Int Rpt
HNVEGFTERRE DVL3_MOUSE 453 82 -
HNVEGFTDRRE DVL3_HUMAN 453 82 -
HNVEGFTDRRE Q9UG07 285 82 -
HHVEGFPERRE DVL2_HUMAN 464 75 -
HHVEGFTDRRE Q9DGC7 459 82 -
HHVEGFPERRE DVL2_MOUSE 464 75 -
HHVEGFQDRRE DVL2_XENLA 459 83 -
THVEGFKERRE DVL1_HUMAN 431 58 -
THVEGFKERRE DVLL_HUMAN 431 58 -
THVEGFKERRE DVL1_MOUSE 456 83 -
ENVEDVQDRRE DSH_DROME 435 61 -
ENVEDVQDRRE Q9VYZ9 435 61 -
AHVDGFQDRRD Q9GTJ8 434 88 -
QKVHGLTERRD Q9NL46 410 77 -
DHVEGLRERKT Q18467 310 15 -
DHVEGLRERKT Q95ZX3 442 15 -
DHVEGLRERKT Q95ZX4 442 15 -

Motif 4 width=12
Element Seqn Id St Int Rpt
HTVNKITFSEQC DVL3_MOUSE 479 15 -
HTVNKITFSEQC DVL3_HUMAN 479 15 -
HTVNKITFSEQC Q9UG07 311 15 -
HTVNKITFSEQC DVL2_HUMAN 490 15 -
HTVNKITFSEQC Q9DGC7 485 15 -
HTVNKITFSEQC DVL2_MOUSE 490 15 -
HTVNKITFSEQC DVL2_XENLA 485 15 -
HTVNKITFSEQC DVL1_HUMAN 457 15 -
HTVNKITFSEQC DVLL_HUMAN 457 15 -
HTVNKITFSEQC DVL1_MOUSE 482 15 -
HTVNKLTFSEQC DSH_DROME 461 15 -
HTVNKLTFSEQC Q9VYZ9 461 15 -
HTVKKVTFSEQC Q9GTJ8 460 15 -
HTVNKITFSEQC Q9NL46 436 15 -
HVVNKVTFTEQC Q18467 336 15 -
HVVNKVTFTEQC Q95ZX3 468 15 -
HVVNKVTFTEQC Q95ZX4 468 15 -