GAPVD1
Description
The GAPVD1 (GTPase activating protein and VPS9 domains 1) is a protein-coding gene located on chromosome 9.
GTPase activating protein and VPS9 domains 1, also known as GAPVD1, Gapex-5 and RME-6 is a protein which in humans is encoded by the GAPVD1 gene. GAPVD1 is Rab GTPase guanine nucleotide exchange factor essential for activation of RAB5A during engulfment of apoptotic cells. GAPVD1 is also involved in the degradation of the epidermal growth factor receptor. Gapex-5 mediated activation of Rab5 has been implicated in the insulin stimulated formation of plasma membrane phosphatidylinositol-3-phosphate. Based on sequence homology, mammalian Gapex-5 has been shown to have an amino-terminal Ras GAP domain, a central polyproline (SH3 binding) region and a carboxy-terminal Rab GEF domain. The RabGEF domain has been suggested to activate Rab5 and Rab31.
GAPVD1 acts as both a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), playing a crucial role in various cellular processes. It acts as a GEF for RAB31, facilitating the exchange of GDP for GTP, which regulates the trafficking of LC2A4/GLUT4. In the absence of insulin, GAPVD1 keeps RAB31 active, leading to a continuous cycle between LC2A4/GLUT4 storage vesicles and early endosomes, effectively retaining LC2A4/GLUT4 within the cell. Upon insulin stimulation, GAPVD1 translocates to the plasma membrane, releasing LC2A4/GLUT4 from storage vesicles. Furthermore, GAPVD1 is involved in EGFR trafficking and degradation, potentially by promoting EGFR ubiquitination and subsequent proteasomal degradation. It exhibits GEF activity for Rab5 and GAP activity for Ras.
GAPVD1 is also known as GAPEX5, GAPex-5, RAP6.
