RACGAP1
Description
The RACGAP1 (Rac GTPase activating protein 1) is a protein-coding gene located on chromosome 12.
Rac GTPase-activating protein 1 is an enzyme that in humans is encoded by the RACGAP1 gene.
== Function == Rho GTPases control a variety of cellular processes. There are 3 subtypes of Rho GTPases in the Ras superfamily of small G proteins: RHO (see MIM 165370), RAC (see RAC1; MIM 602048), and CDC42 (MIM 116952). GTPase-activating proteins (GAPs) bind activated forms of Rho GTPases and stimulate GTP hydrolysis. Through this catalytic function, Rho GAPs negatively regulate Rho-mediated signals. GAPs may also serve as effector molecules and play a role in signaling downstream of Rho and other Ras-like GTPases.[supplied by OMIM]. Over-expression of RACGAP1 is observed in multiple human cancers including breast cancer, gastric cancer and colorectal cancer. Evidence show that RACGAP1 can modulate mitochondrial quality control by stimulating mitopahy and mitochondrial biogenesis in breast cancer. Knocking out RACGAP1 in vitro using CRISPR/Cas9 leads to cytokinesis failure.
== Interactions == RACGAP1 has been shown to interact with ECT2, Rnd2 and SLC26A8.
RACGAP1 is a component of the centralspindlin complex, a microtubule-dependent and Rho-mediated signaling complex crucial for myosin contractile ring formation during cytokinesis. It ensures proper attachment of the midbody to the cell membrane during cytokinesis by sequentially binding to ECT2 and RAB11FIP3, which regulate cleavage furrow ingression and abscission during cytokinesis. RACGAP1 plays key roles in controlling cell growth and differentiation of hematopoietic cells, independent of its Rac GTPase regulation. It is essential for erythropoiesis, and also involved in regulating growth-related processes in adipocytes and myoblasts. It may be involved in regulating spermatogenesis and neuronal proliferation. RACGAP1 exhibits strong GAP activity towards CDC42 and RAC1, and less towards RHOA. It is essential for early embryogenesis, may play a role in regulating cortical activity through RHOA during cytokinesis, and may participate in the regulation of sulfate transport in male germ cells.
RACGAP1 is also known as CDAN3B, CYK4, HsCYK-4, ID-GAP, MgcRacGAP.
Associated Diseases
- Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive
- Congenital dyserythropoietic anemia type III
