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2  structures 426  species 1  interaction 1733  sequences 66  architectures

Family: DOCK-C2 (PF14429)

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 [1].

Literature references

  1. 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

  2. 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

External database links

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- 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 DHR-1 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 DHR-1 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].

The DHR-2 domain is a GEF catalytic domain of ~400 residues situated within the C terminus. The structure of the DHR2 domain differs from that of other GEF catalytic domains. It is organised into three lobes of roughly equal size (lobes A, B, and C), with the Rho-family binding site and catalytic centre generated entirely from lobes B and C. Lobe A is formed from an antiparallel array of alpha helices. Through extensive contacts with lobe B, lobe A stabilises the DHR2 domain. Lobe B adopts an unusual architecture of two antiparallel beta sheets disposed in a loosely packed orthogonal arrangement, whereas lobe C comprises a four-helix bundle [PUBMED:19745154, PUBMED:21613211].

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.

Domain organisation

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

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Pfam Clan

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 10 members:

Aida_C2 B9-C2 C2 C2-C2_1 CC2D2AN-C2 CEP76-C2 DOCK-C2 NT-C2 PI3K_C2 PTEN_C2


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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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Seed source: Mannual
Previous IDs: none
Type: Family
Author: Zhang D, Aravind L
Number in seed: 241
Number in full: 1733
Average length of the domain: 186.20 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 10.13 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.3 25.3
Trusted cut-off 25.3 26.1
Noise cut-off 25.2 24.6
Model length: 171
Family (HMM) version: 2
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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There is 1 interaction for this family. More...



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 2 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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