DOCK7
Description
The DOCK7 (dedicator of cytokinesis 7) is a protein-coding gene located on chromosome 1.
DOCK7, a large (~240 kDa) protein encoded by the DOCK7 gene in humans, is involved in intracellular signaling pathways. It belongs to the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs), which act as activators of small G-proteins. Dock7 activates isoforms of the small G protein Rac. DOCK7 was identified as one of several proteins exhibiting significant sequence similarity to Dock180, the founding member of the DOCK family. DOCK7 expression has been observed in neurons and the HEK 293 cell line. DOCK7, like other GEFs, participates in cellular signaling by activating small G proteins. In their inactive state, G proteins are bound to Guanosine diphosphate (GDP). Activation requires the release of GDP and binding of guanosine triphosphate (GTP). GEFs facilitate this nucleotide exchange, thereby activating G proteins. DOCK7 and other members of the DOCK family differ from conventional GEFs in that they lack the canonical structure of tandem DH-PH domains, known to induce nucleotide exchange. Instead, they possess a DHR2 domain responsible for G protein activation by stabilizing it in its nucleotide-free state.
DOCK7 acts as a guanine nucleotide exchange factor (GEF) that activates Rac1 and Rac3 Rho small GTPases by replacing bound GDP with free GTP. It lacks GEF activity towards CDC42. DOCK7 is essential for STMN1 'Ser-15' phosphorylation during axon formation, contributing to neuronal polarization. As part of the DISP complex, it may regulate the association of septins with actin, impacting actin cytoskeleton regulation. DOCK7 is implicated in pigmentation and plays a role in regulating cortical neurogenesis by controlling radial glial cell (RGC) proliferation and differentiation. It negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by opposing the microtubule growth-promoting function of TACC3.
DOCK7 is also known as DEE23, EIEE23, ZIR2.
Associated Diseases
- Developmental and epileptic encephalopathy 23
- Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome
