Protein Domain : Dedicator of cytokinesis protein 4, DHR2 domain IPR037014

Type	Domain
Description	DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases [ ]. DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis. The N-terminal SH3 domain of the DOCK proteins functions as an inhibitor of GEF, which can be relieved upon its binding to the ELMO1-3 adaptor proteins, after their binding to active RhoG at the plasma membrane [, ]. DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11) []. All DOCKs contain two homology domains: the DHR-1 (Dock homology region-1), also called CZH1 (CED-5, Dock180, and MBC-zizimin homology 1), and DHR-2 (also called CZH2 or Docker). DOCK4 is an atypical guanine nucleotide exchange factor (GEF) that lacks the conventional Dbl homology (DH) domain. It activates small GTPases by exchanging bound GDP for free GTP. It plays a role in regulating dendritic growth and branching in hippocampal neurons, where it is highly expressed. It may also regulate spine morphology and synapse formation [ ] and has been linked to autism, dyslexia, and schizophrenia [, , ]. DOCK4 activates the Ras family GTPase Rap1, probably indirectly through interaction with Rap regulatory proteins. DOCK4 plays a critical role in mediating TGF-beta's prometastatic effects in lung cancer [].This entry represents the DHR-2 domain of DOCK4, which contains the catalytic GEF activity for Rac and/or Cdc42.
Short Name	DHR2_DOCK4