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

General

GTPase-activating protein (GAP) guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS)

Properties

SIZE: entity length = 1478 aa MW = 165 kD MOTIF: ras-GAP domain NAME: ras-GAP domain SITE: 131-353 Thr phosphorylation site {T390} Ser phosphorylation site {S742} Ser phosphorylation site {S746} Thr phosphorylation site {T747} Ser phosphorylation site {S748} Ser phosphorylation site {S903} Ser phosphorylation site {S966} Ser phosphorylation site {S1096} Ser phosphorylation site {S1105} VPS9 {1338-1478}

Database Correlations

UniProt Q14C86 PFAM correlations Kegg hsa:2613

References

UniProt :accession Q14C86