Dock10

Dock10 ( D edicator o f c yto k inesis), also known as Zizimin3, is a large (~240 kDa) is_associated_with::protein involved in is_associated_with::intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of is_associated_with::guanine nucleotide exchange factors, which function as activators of small is_associated_with::G proteins.

Discovery
Dock10 was identified via is_associated_with::bioinformatic approaches as one of a family of is_associated_with::evolutionarily conserved proteins (the DOCK family) that share significant is_associated_with::sequence homology. Dock10 is expressed in peripheral blood is_associated_with::leukocytes as well as in the is_associated_with::brain, is_associated_with::spleen, is_associated_with::lung and is_associated_with::thymus.

Structure and Function
Dock10 shares the same domain arrangement as other members of the DOCK-D/Zizimin subfamily as well as a high level of sequence similarity. It contains a is_associated_with::DHR2 domain that is involved in G protein binding and a is_associated_with::DHR1 domain, which, in some DOCK family proteins, interacts with membrane is_associated_with::phospholipids. Like other DOCK-D subfamily proteins Dock10 contains an is_associated_with::N-terminal is_associated_with::PH domain, which, in Dock9/Zizimin1, mediates recruitment to the is_associated_with::plasma membrane. The DHR2 domain of Dock10 appears to bind to the small G proteins is_associated_with::Cdc42, TC10 and TCL although these interactions are of low affinity. The physiological role of Dock10 is poorly characterised, however a study in is_associated_with::lymphocytes has shown that Dock10 expression is upregulated in is_associated_with::B-lymphocytes and is_associated_with::Chronic Lymphocytic Leukemia (CLL) cells in response to the is_associated_with::cytokine IL-4. This suggests that Dock10 may have a role in B-cell activation and proliferation. Another study identified Dock10 as a protein that was overexpressed in some aggressive is_associated_with::papillary thyroid carcinomas.