ARHGAP26 (Rho GTPase Activating Protein 26), also known as GRAF (GTPase Regulator Associated with FAK), is a Rho GTPase-activating protein encoded by the ARHGAP26 gene, located on chromosome 5q31. The protein has a molecular weight of approximately 110 kDa and is primarily localized to the cytoplasm and cytoskeleton. ARHGAP26 belongs to the Rho GTPase-activating protein family and contains multiple functional domains including an N-terminal SH3 domain for protein-protein interactions, a RhoGAP domain that provides GTPase activity, and a focal adhesion targeting (FAT) domain. The RhoGAP domain is catalytic, accelerating the intrinsic GTPase activity of Rho family GTPases, converting them from active GTP-bound to inactive GDP-bound states. ARHGAP26 primarily regulates RhoA, Rac1, and Cdc42, which control actin cytoskeleton dynamics, cell adhesion, migration, and synaptic plasticity. Dysregulation of ARHGAP26 has been implicated in amyotrophic lateral sclerosis (ALS) and myeloid leukemia.
ARHGAP26 (also known as GRAF - GTPase Regulator Associated with FAK) contains multiple functional domains:
The RhoGAP domain is catalytic, accelerating the intrinsic GTPase activity of Rho family GTPases, converting them from active GTP-bound to inactive GDP-bound states.
ARHGAP26 is a Rho GTPase-activating protein (GAP) that regulates the activity of Rho family small GTPases, primarily RhoA, Rac1, and Cdc42. These GTPases control:
In neurons, ARHGAP26 is involved in:
Rho GTPase signaling pathways are being explored as therapeutic targets for neurodegenerative diseases. While ARHGAP26 itself is not a direct target, modulating Rho GTPase activity could potentially be beneficial for: