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0  structures 74  species 0  interactions 215  sequences 14  architectures

Family: Dishevelled (PF02377)

Summary: Dishevelled specific domain

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Dishevelled Edit Wikipedia article

Dishevelled specific domain
PBB Protein DVL1 image.jpg
Solution structure of the mouse Dvl-1 DEP domain based on the PDB 1fsh coordinates.
Identifiers
Symbol Dishevelled
Pfam PF02377
InterPro IPR003351
PROSITE PDOC50841

Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors.[1] It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs.[2]

Dishevelled plays important roles in both the embryo and the adult, ranging from cellular differentiation and cell polarity to social behavior.[2]

Members[edit]

There are three human genes that encode dishevelled proteins:[3]

Overview of signal transduction pathways involved in apoptosis.

References[edit]

  1. ^ Penton A, Wodarz A, Nusse R (June 2002). "A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin". Genetics 161 (2): 747–62. PMC 1462152. PMID 12072470. 
  2. ^ a b Wallingford JB, Habas R (October 2005). "The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity". Development 132 (20): 4421–36. doi:10.1242/dev.02068. PMID 16192308. 
  3. ^ Lee YN, Gao Y, Wang HY (February 2008). "Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, -2, and -3". Cell. Signal. 20 (2): 443–52. doi:10.1016/j.cellsig.2007.11.005. PMC 2233603. PMID 18093802. 

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Dishevelled specific domain Provide feedback

This domain is specific to the signaling protein dishevelled. The domain is found adjacent to the PDZ domain PF00595 often in conjunction with DEP (PF00610) and DIX (PF00778).

Literature references

  1. Theisen H, Purcell J, Bennett M, Kansagara D, Syed A, Marsh JL; , Development 1994;120:347-360.: dishevelled is required during wingless signaling to establish both cell polarity and cell identity. PUBMED:8149913 EPMC:8149913


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003351

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) [PUBMED:9891778]. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [PUBMED:10967351].

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 [PUBMED:10733430]. More recently, however, several non-canonical Wnt signalling pathways have been elucidated that act independently of B-catenin. In both cases, the transduction mechanism requires dishevelled protein (Dsh), a cytoplasmic phosphoprotein that acts directly downstream of frizzled [PUBMED:12072470]. 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 dispensable for Wg signalling, it is thought to be important in planar polarity signalling in flies [PUBMED:12072470]).

This domain is specific to the signalling protein dishevelled. In Drosophila melanogaster, the dishevelled segment polarity protein is required to establish coherent arrays of polarized cells and segments in embryos. It plays a role in wingless signalling, possibly through the reception of the wingless signal by target cells and subsequent redistribution of arm protein in response to that signal in embryos.The domain is found adjacent to the PDZ domain (INTERPRO), often in conjunction with DEP (INTERPRO) and DIX (INTERPRO).

Domain organisation

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Alignments

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(4)
Full
(215)
Representative proteomes NCBI
(198)
Meta
(0)
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(17)
RP35
(27)
RP55
(58)
RP75
(107)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(4)
Full
(215)
Representative proteomes NCBI
(198)
Meta
(0)
RP15
(17)
RP35
(27)
RP55
(58)
RP75
(107)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(4)
Full
(215)
Representative proteomes NCBI
(198)
Meta
(0)
RP15
(17)
RP35
(27)
RP55
(58)
RP75
(107)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_1381 (release 5.2)
Previous IDs: none
Type: Family
Author: Mian N, Bateman A
Number in seed: 4
Number in full: 215
Average length of the domain: 70.60 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 10.92 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.7 19.7
Trusted cut-off 19.7 19.7
Noise cut-off 18.7 18.7
Model length: 73
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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