Summary: C2 domain in Dock180 and Zizimin proteins
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C2 domain in Dock180 and Zizimin proteins Provide feedback
The Dock180/Dock1 and Zizimin proteins are atypical GTP/GDP exchange factors for the small GTPases Rac and Cdc42 and are implicated cell-migration and phagocytosis. Across all Dock180 proteins, two regions are conserved: C-terminus termed CZH2 or DHR2 (or the Dedicator of cytokinesis) whereas CZH1/DHR1 contain a new family of the C2 domain .
Zhang D, Aravind L;, Gene. 2010;469:18-30.: Identification of novel families and classification of the C2 domain superfamily elucidate the origin and evolution of membrane targeting activities in eukaryotes. PUBMED:20713135 EPMC:20713135
Premkumar L, Bobkov AA, Patel M, Jaroszewski L, Bankston LA, Stec B, Vuori K, Cote JF, Liddington RC;, J Biol Chem. 2010;285:13211-13222.: Structural basis of membrane targeting by the Dock180 family of Rho family guanine exchange factors (Rho-GEFs). PUBMED:20167601 EPMC:20167601
Internal database links
|Similarity to PfamA using HHSearch:||Aida_C2|
This tab holds annotation information from the InterPro database.
InterPro entry IPR027007
Rho guanosine triphosphatases (GTPases) are critical regulators of cell motility, polarity, adhesion, cytoskeletal organisation, proliferation, gene expression, and apoptosis. Conversion of these biomolecular switches to the activated GTP-bound state is controlled by two families of guanine nucleotide exchanges factors (GEFs). DH-PH proteins are a large group of Rho GEFs comprising a catalytic Dbl homology (DH) domain with an adjacent pleckstrin homology (PH) domain within the context of functionally diverse signalling modules. The evolutionarily distinct and smaller family of DOCK (dedicator of cytokinesis) or CDM (CED-5, DOCK1180, Myoblast city) proteins activate either Rac or Cdc42 to control cell migration, morphogenesis, and phagocytosis. DOCK proteins share the DOCK-type C2 domain (also termed the DOCK-homology region (DHR)-1 or CDM-zizimin homology 1 (CZH1) domain and the DHR-2 domain (also termed the CZH2 or DOCKER domain), [ PUBMED:20713135 , PUBMED:12172552 , PUBMED:12432077 , PUBMED:20167601 , PUBMED:19745154 , PUBMED:21613211 ].
The ~200 residue DOCK-type C2 domain is located toward the N terminus. It adopts a C2-like architecture and interacts with phosphatidylinositol 3,4,5-trisphosphate [ PUBMED:19745154 ] to mediate signalling and membrane localization. The central core of the DOCK-type C2 domain domain adopts an antiparallel beta-sandwich with the "type II" C2 domain fold (a circular permutation of the more common "type I" topology), in which two 4-stranded sheets with strand order 6-5-2-3 and 7-8-1-4 create convex- and concave-exposed faces, respectively [ PUBMED:20167601 ].
Some DOCK proteins are listed below:
- Mammalian Mammalian dedicator of cytokinesis 180 (DOCK180 or DOCK1), important for cell migration.
- Mammalian DOCK2, important for lymphocyte development, homong, activation, adhesion, polarization and migration processes.
- Mammalian DOCK3 (also known as MOCA), is expressed predominantly in neurons and resides in growth cones and membrane ruffles.
- Mammalian DOCK4, possesses tumor suppressor properties.
- Mammalian DOCK9 (zizimin1), plays an important role in dendrite growth in hippocampal neurons through activation of Cdc42.
- Drosophila melanogaster Myoblast city.
- Caenorhabditis elegans CED-5.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This family is a member of clan C2 (CL0154), which has the following description:
This superfamily includes C2 domains and C2-like domains.
The clan contains the following 18 members:Aida_C2 Anillin B9-C2 C2 C2-C2_1 CC2D2AN-C2 CEP76-C2 DOCK-C2 IcmF_C MNNL NT-C2 PI3K_C2 PTEN_C2 pYEATS RPGR1_C SPATA6 Spond_N YEATS
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Author:||Zhang D , Aravind L|
|Number in seed:||183|
|Number in full:||10538|
|Average length of the domain:||184.9 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||9.91 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||9|
|Download:||download the raw HMM for this family|
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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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 DOCK-C2 domain has been found. There are 9 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 sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.