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9  structures 1305  species 0  interactions 10538  sequences 179  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

Internal 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-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.

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 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


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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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.

Representative proteomes UniProt
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Representative proteomes UniProt

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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.

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

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


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: Mannual
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 33.6 33.6
Trusted cut-off 33.6 33.6
Noise cut-off 33.5 33.5
Model length: 188
Family (HMM) version: 9
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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.

Protein Predicted structure External Information
A0A044RAA8 View 3D Structure Click here
A0A044SZE1 View 3D Structure Click here
A0A077Z963 View 3D Structure Click here
A0A077ZCY1 View 3D Structure Click here
A0A0B4K7Q6 View 3D Structure Click here
A0A0D2G7J4 View 3D Structure Click here
A0A0G2JV16 View 3D Structure Click here
A0A0G2K3H2 View 3D Structure Click here
A0A0G2KAH4 View 3D Structure Click here
A0A0K0ELS6 View 3D Structure Click here
A0A0K0EPK7 View 3D Structure Click here
A0A0K3AR51 View 3D Structure Click here
A0A0N4UD94 View 3D Structure Click here
A0A0R4IEH3 View 3D Structure Click here
A0A0R4IUA6 View 3D Structure Click here
A0A158N8G2 View 3D Structure Click here
A0A158Q4H1 View 3D Structure Click here
A0A175W2J9 View 3D Structure Click here
A0A1C1CIG7 View 3D Structure Click here
A0A1D6K1C7 View 3D Structure Click here
A0A1D6PBC1 View 3D Structure Click here
A0A2R8PX59 View 3D Structure Click here
A0A2R8Q6D5 View 3D Structure Click here
A0A2R8QA05 View 3D Structure Click here
A0A3P7DQI6 View 3D Structure Click here
A0A3P7EF67 View 3D Structure Click here
A0A3P7FD72 View 3D Structure Click here
A0A3P7PXJ0 View 3D Structure Click here
A0A3Q0KDW4 View 3D Structure Click here
A0A5K4F4K1 View 3D Structure Click here
A2AF47 View 3D Structure Click here
A4I448 View 3D Structure Click here
B0R034 View 3D Structure Click here
B2RY04 View 3D Structure Click here
B8JID6 View 3D Structure Click here
C0NSU3 View 3D Structure Click here
C1GP24 View 3D Structure Click here
D3ZZW1 View 3D Structure Click here
E7F0I2 View 3D Structure Click here
F1LPG2 View 3D Structure Click here