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16  structures 308  species 2  interactions 2616  sequences 134  architectures

Family: DEP (PF00610)

Summary: Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)

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This is the Wikipedia entry entitled "DEP domain". More...

DEP domain Edit Wikipedia article

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
PDB 1fsh EBI.jpg
structural basis of the recognition of the dishevelled dep domain in the wnt signaling pathway
Identifiers
Symbol DEP
Pfam PF00610
InterPro IPR000591

In molecular biology, the DEP domain (Dishevelled, Egl-10 and Pleckstrin domain) is a globular protein domain of about 80 amino acids that is found in over 50 proteins involved in G-protein signalling pathways. It was named after the three proteins it was initially found in:

Mammalian regulators of G-protein signalling also contain these domains, and regulate signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving them into their inactive GDP-bound form. It has been proposed that the DEP domain could play a selective role in targeting DEP domain-containing proteins to specific subcellular membranous sites, perhaps even to specific G protein-coupled signaling pathways.[2][3] Nuclear magnetic resonance spectroscopy has revealed that the DEP domain comprises a three-helix bundle, a beta-hairpin 'arm' composed of two beta-strands and two short beta-strands in the C-terminal region.[3]

References[edit]

  1. ^ Masuho, I.; Wakasugi-Masuho, H.; Posokhova, E. N.; Patton, J. R.; Martemyanov, K. A. (2011). "Type 5 G Protein   Subunit (G 5) Controls the Interaction of Regulator of G Protein Signaling 9 (RGS9) with Membrane Anchors". Journal of Biological Chemistry 286 (24): 21806–21813. doi:10.1074/jbc.M111.241513. PMC 3122235. PMID 21511947.  edit
  2. ^ Burchett SA (October 2000). "Regulators of G protein signaling: a bestiary of modular protein binding domains". J. Neurochem. 75 (4): 1335–51. doi:10.1046/j.1471-4159.2000.0751335.x. PMID 10987813. 
  3. ^ a b Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J (December 2000). "Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway". Nat. Struct. Biol. 7 (12): 1178–84. doi:10.1038/82047. PMID 11101902. 

This article incorporates text from the public domain Pfam and InterPro IPR000591

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.

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) Provide feedback

The DEP domain [1] is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell [2-3]. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting [4-5]. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit [6-7].

Literature references

  1. Ponting CP, Bork P , Trends Biochem Sci 1996;21:245-246.: Pleckstrin's repeat performance: a novel domain in G-protein signaling? PUBMED:8755244 EPMC:8755244

  2. Martemyanov KA, Lishko PV, Calero N, Keresztes G, Sokolov M, Strissel KJ, Leskov IB, Hopp JA, Kolesnikov AV, Chen CK, Lem J, Heller S, Burns ME, Arshavsky VY; , J Neurosci 2003;23:10175-10181.: The DEP domain determines subcellular targeting of the GTPase activating protein RGS9 in vivo. PUBMED:14614075 EPMC:14614075

  3. Keresztes G, Martemyanov KA, Krispel CM, Mutai H, Yoo PJ, Maison SF, Burns ME, Arshavsky VY, Heller S; , J Biol Chem 2004;279:1581-1584.: Absence of the RGS9.Gbeta5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse. PUBMED:14625292 EPMC:14625292

  4. Pan WJ, Pang SZ, Huang T, Guo HY, Wu D, Li L; , Cell Res. 2004;14:324-330.: Characterization of function of three domains in dishevelled-1: DEP domain is responsible for membrane translocation of dishevelled-1. PUBMED:15353129 EPMC:15353129

  5. Kovoor A, Seyffarth P, Ebert J, Barghshoon S, Chen CK, Schwarz S, Axelrod JD, Cheyette BN, Simon MI, Lester HA, Schwarz J; , J Neurosci. 2005;25:2157-2165.: D2 dopamine receptors colocalize regulator of G-protein signaling 9-2 (RGS9-2) via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated with dopamine pathways. PUBMED:15728856 EPMC:15728856

  6. Ballon DR, Flanary PL, Gladue DP, Konopka JB, Dohlman HG, Thorner J; , Cell. 2006;126:1079-1093.: DEP-domain-mediated regulation of GPCR signaling responses. PUBMED:16990133 EPMC:16990133

  7. Chen S, Hamm HE; , Dev Cell. 2006;11:436-438.: DEP domains: More than just membrane anchors. PUBMED:17011483 EPMC:17011483


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000591

This entry represents the DEP (Dishevelled, Egl-10 and Pleckstrin) domain, a globular domain of about 80 residues that is found in over 50 proteins involved in G-protein signalling pathways. It was named after the three proteins it was initially found in:

  • Dishevelled (Dsh and Dvl), which play a key role in the transduction of the Wg/Wnt signal from the cell surface to the nucleus; it is a segment polarity protein required to establish coherent arrays of polarized cells and segments in embryos, and plays a role in wingless signalling.
  • Egl-10, which regulates G-protein signalling in the central nervous system.
  • Pleckstrin, the major substrate of protein kinase C in platelets; Pleckstrin contains two PH domains flanking the DEP domain.

Mammalian regulators of G-protein signalling also contain these domains, and regulate signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving them into their inactive GDP-bound form. It has been proposed that the DEP domain could play a selective role in targeting DEP domain-containing proteins to specific subcellular membranous sites, perhaps even to specific G protein-coupled signaling pathways [PUBMED:10987813, PUBMED:11101902]. Nuclear magnetic resonance spectroscopy has revealed that the DEP domain comprises a three-helix bundle, a beta-hairpin 'arm' composed of two beta-strands and two short beta-strands in the C-terminal region [PUBMED:11101902].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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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
(133)
Full
(2616)
Representative proteomes NCBI
(2411)
Meta
(15)
RP15
(410)
RP35
(638)
RP55
(1072)
RP75
(1545)
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  Seed
(133)
Full
(2616)
Representative proteomes NCBI
(2411)
Meta
(15)
RP15
(410)
RP35
(638)
RP55
(1072)
RP75
(1545)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(133)
Full
(2616)
Representative proteomes NCBI
(2411)
Meta
(15)
RP15
(410)
RP35
(638)
RP55
(1072)
RP75
(1545)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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Curation and family details

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Curation View help on the curation process

Seed source: SMART
Previous IDs: none
Type: Domain
Author: Ponting C, Schultz J, Bork P, Martemyanov K, Thorner J
Number in seed: 133
Number in full: 2616
Average length of the domain: 72.20 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 9.41 %

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 21.9 21.9
Trusted cut-off 21.9 22.0
Noise cut-off 21.8 21.8
Model length: 74
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

WD40 RasGEF

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DEP domain has been found. There are 16 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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