The huntingtin family consists of huntingtin proteins, including Dictyostelium HD protein homologue. Abnormalities in the huntingtin protein (Htt) are associated with Huntington's disease [], but despite its importance the function of Htt is largely unknown. In Dictyostelium discoideum Htt is required for normal chemotaxis and cytokinesis [].
This repeated domain is less than 40 amino acids in length and is present in huntingtin protein (Htt). Htt is expressed in many tissues, with various expression levels and is involved in a number of cellular functions. However, its exact function is not yet clear. An abnormal polyglutamine (polyQ) expansion in this protein causes Huntington's disease (HD), a progressive autosomal-dominant neurodegenerative disease characterised by an uncontrolled motor movement known as chorea, cognitive disorder and depression []. Htt consists of multiple HEAT repeats organised in N-terminal, bridge and C-terminal domains [, ], which function as a scaffold that mediates interactions with binding partners. This domain connects the N- and C-HEAT domains.
There are two forms of Pix proteins: alpha Pix (also called Rho guanine nucleotide exchange factor (GEF) 6, 90Cool-2 or ARHGEF6) and beta Pix (GEF7, p85Cool-1 or ARHGEF7), which activate small GTPases by exchanging bound GDP for free GTP. betaPix contains an N-terminal SH3 domain, a RhoGEF/DH domain, a PH domain, a GIT1 binding domain (GBD), and a C-terminal coiled-coil (CC) domain []. It acts as a GEF for both Cdc42 and Rac1 [], and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion [, , , ]. alphaPix differs in that it contains a calponin homology (CH) domain, which interacts with beta-parvin, N-terminal to the SH3 domain. alphaPix is an exchange factor for Rac1 and Cdc42 and mediates Pak activation on cell adhesion to fibronectin. Mutations in alphaPix can cause X-linked mental retardation. alphaPix also interacts with Huntington's disease protein (htt), and enhances the aggregation of mutant htt (muthtt) by facilitating SDS-soluble muthtt-muthtt interactions. The DH-PH domain of a Pix was required for its binding to htt. In the majority of Rho GEF proteins, the DH-PH domain is responsible for the exchange activity [, , , , ].This entry represents the PH domain of ARHGEF6 and ARHGEF7.
