GTPase-activating protein & VPS9 domain-containing protein 1 (Rab5-activating protein 6, GAPex-5, GAPVD1, GAPEX5, KIAA1521 RAP6)

Function

• acts both as a GTPase-activating protein (GAP) & a guanine nucleotide exchange factor (GEF)
• participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking
• acts as a GEF for the Ras-related protein RAB31 by exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 trafficking
• in the absence of insulin, it maintains RAB31 in an active state & promotes a futile cycle between LC2A4/GLUT4 storage vesicles & early endosomes, retaining LC2A4/GLUT4 inside the cells
• upon insulin stimulation, it is translocated to the plasma membrane, releasing LC2A4/GLUT4 from intracellular storage vesicles
• also involved in EGFR trafficking & degradation, possibly by promoting EGFR ubiquitination & subsequent degradation by the proteasome
• has GEF activity for Rab5 & GAP activity for Ras
• interacts with TRIP10/CIP4 (putative)
• interacts with RAB5A
• phosphorylated upon DNA damage, probably by ATM or ATR

Structure

• belongs to the GAPVD1 family
• contains 1 Ras-GAP domain
• contains 1 VPS9 domain

Compartment

• peripheral membrane, endosome

recruited to the plasma membrane by TRIP10/CIP4 in response to insulin

Alternative splicing

named isoforms=6

More general terms

• GTPase-activating protein (GAP)
• guanine nucleotide exchange factor

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2613
• UniProt: http://www.uniprot.org/uniprot/Q14C86.html