ARHGEF12


Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene. This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor.

Function

Rho guanine nucleotide exchange factor 12 is guanine nucleotide exchange factor for the RhoA small GTPase protein. Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions. In particular, active Rho is a major regulator of the cell actin cytoskeleton.
RhoGEF12 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins. The others are ARHGEF1, ARHGEF11 and AKAP13. GPCR-regulated RhoGEF12 acts as an effector for G12 and G13 G proteins. In addition to being activated by G12 or G13 G proteins, three of these four RhoGEF proteins also function as RGS family GTPase-activating proteins to increase the rate of GTP hydrolysis of G12/G13 alpha proteins. This action increases the rate of G protein deactivation, limiting the time during which these RhoGEFs activate Rho.

Clinical significance

This protein is observed to form myeloid/lymphoid fusion partner in acute myeloid leukemia.

Interactions

ARHGEF12 has been shown to interact with: