Dedicator of cytokinesis protein 11 (DOCK11)
The protein contains 2073 amino acids for an estimated molecular weight of 237671 Da.
Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP. Required for marginal zone (MZ) B-cell development, is associated with early bone marrow B-cell development, MZ B-cell formation, MZ B-cell number and marginal metallophilic macrophages morphology. Facilitates filopodia formation through the activation of CDC42. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs16995229 |
No binding partner found
The reference OMIM entry for this protein is 300681
Dedicator of cytokinesis 11; dock11
Activated cdc42-associated guanine nucleotide exchange factor; acg
Zizimin 2; ziz2
CLONING
By database analysis with DOCK1 (601403) sequence as query, Cote and Vuori (2002) identified DOCK11. DOCK11 is a member of the DOCKD subfamily, which also includes DOCK9 (607325) and DOCK10 (611518). Members of the DOCKD subfamily contain an N-terminal PH domain and conserved DOCK-homology regions, DHR1 and DHR2, also known as CZH1 and CZH2 (see 607325). By subtractive hybridization to identify genes upregulated in germinal center B-cells compared to nongerminal center B-cells, followed by PCR of splenic B cell cDNA, Nishikimi et al. (2005) cloned mouse Dock11, which they called zizimin-2. They identified human DOCK11 by database analysis. The deduced 2,073-amino acid human protein shares 96% amino acid identity with the mouse protein. Quantitative RT-PCR of normal mouse tissues detected Dock11 expression in spleen, thymus, bone marrow, and peripheral blood lymphocytes. RT-PCR demonstrated a 2.6-fold increase in mouse Dock11 expression in germinal center B cells compared to nongerminal center B cells and detected high Dock11 expression in B-cell lines, intermediate expression in myoblasts, and low expression in fibroblasts, neuroblasts and neuroblastoma cell lines.GENE FUNCTION
Nishikimi et al. (2005) showed that overexpressed mouse Dock11 induced activation of endogenous Cdc42 (116952) in COS-1 cells via the CZH2 domain. Binding assays showed that Dock11 selectively bound Cdc42 but not other Rho GTPases, such as TC10 (RHOQ; 605857) or TCL (RHOJ; 607653). Lin et al. (2006) confirmed that DOCK11 is a specific guanine nucleotide exchange factor (GEF) for Cdc42, with GEF activity originating from the DHR2/CZH2 domain. GST pull-down assays demonstrated that DOCK11 formed stable complexes with activated forms of Cdc42. Deletion analysis found that DOCK11 amino acids 66 to 126 formed an activated Cdc42-binding (ACB) domain that did not include the N-terminal PH domain. Coimmunoprecipitation studies showed an interaction between the ACB and DHR2/CZH2 domains that was enhanced by activated Cdc42, suggesting that the ACB and DHR2/CZH2 domains form a high affinity binding site for activated Cdc42. Overexpression of full-length DOCK11 in COS-7 cells induced multiple microspike structures characteristic of Cdc42 activation that were not seen in cells overexpressing the DHR2/CZH2 domain or DOCK11 lacking the ACB domain.MAPPING
By database analysis, Cote and Vuori (2002) mapped the DOCK11 gene to the X chromosome. ... More on the omim web site
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 300681 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).