GAPVD1

GTPase activating protein and VPS9 domains 1
Identifiers
Symbols	GAPVD1 ; GAPEX5; GAPex-5; RAP6
External IDs	OMIM: 611714 MGI: 1913941 HomoloGene: 32637 GeneCards: GAPVD1 Gene
Gene ontology Molecular function • guanyl-nucleotide exchange factor activity • GTPase activator activity • GTPase activating protein binding Cellular component • endosome • cytosol • membrane Biological process • endocytosis • signal transduction • positive regulation of GTPase activity • regulation of protein transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	26130	66691
Ensembl	ENSG00000165219	ENSMUSG00000026867
UniProt	Q14C86	Q6PAR5
RefSeq (mRNA)	NM_001282679	NM_025709
RefSeq (protein)	NP_001269608	NP_079985
Location (UCSC)	Chr 9: 125.26 – 125.37 Mb	Chr 2: 34.68 – 34.76 Mb
PubMed search

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.^[1][2]

Function

GAPVD1 is Rab GTPase guanine nucleotide exchange factor essential for activation of RAB5A during engulfment of apoptotic cells.^[3] GAPVD1 is also involved in the degradation of the epidermal growth factor receptor.^[4] Gapex-5 mediated activation of Rab5 has been implicated in the insulin stimulated formation of plasma membrane phosphatidylinositol-3-phosphate.^[5]

Structure

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^[6] and Rab31.^[7]

References

1. "Entrez Gene: GAPVD1 GTPase activating protein and VPS9 domains 1".
2. Hunker CM, Galvis A, Kruk I, Giambini H, Veisaga ML, Barbieri MA (February 2006). "Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis". Biochem. Biophys. Res. Commun. 340 (3): 967–75. doi:10.1016/j.bbrc.2005.12.099. PMID 16410077.
3. Kitano M, Nakaya M, Nakamura T, Nagata S, Matsuda M (May 2008). "Imaging of Rab5 activity identifies essential regulators for phagosome maturation". Nature 453 (7192): 241–5. doi:10.1038/nature06857. PMID 18385674.
4. Su X, Kong C, Stahl PD (July 2007). "GAPex-5 mediates ubiquitination, trafficking, and degradation of epidermal growth factor receptor". J. Biol. Chem. 282 (29): 21278–84. doi:10.1074/jbc.M703725200. PMID 17545148.
5. Lodhi IJ, Bridges D, Chiang SH, Zhang Y, Cheng A, Geletka LM, Weisman LS, Saltiel AR (July 2008). "Insulin Stimulates Phosphatidylinositol 3-Phosphate Production via the Activation of Rab5". Mol. Biol. Cell 19 (7): 2718–28. doi:10.1091/mbc.E08-01-0105. PMC 2441665. PMID 18434594.
6. Su X, Lodhi IJ, Saltiel AR, Stahl PD (September 2006). "Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5". J. Biol. Chem. 281 (38): 27982–90. doi:10.1074/jbc.M602873200. PMID 16880210.
7. Lodhi IJ, Chiang SH, Chang L, Vollenweider D, Watson RT, Inoue M, Pessin JE, Saltiel AR (January 2007). "Gapex-5, a Rab31 Guanine Nucleotide Exchange Factor that Regulates Glut4 Trafficking in Adipocytes". Cell Metab. 5 (1): 59–72. doi:10.1016/j.cmet.2006.12.006. PMC 1779820. PMID 17189207.

Further reading

• Su X, Kong C, Stahl PD (2007). "GAPex-5 mediates ubiquitination, trafficking, and degradation of epidermal growth factor receptor". J. Biol. Chem. 282 (29): 21278–84. doi:10.1074/jbc.M703725200. PMID 17545148.
• Hunker CM, Galvis A, Kruk I; et al. (2006). "Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis". Biochem. Biophys. Res. Commun. 340 (3): 967–75. doi:10.1016/j.bbrc.2005.12.099. PMID 16410077.
• Jin J, Smith FD, Stark C; et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
• Beausoleil SA, Jedrychowski M, Schwartz D; et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Ota T, Suzuki Y, Nishikawa T; et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Nagase T, Kikuno R, Ishikawa K; et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (2): 143–50. doi:10.1093/dnares/7.2.143. PMID 10819331.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Adams MD, Kerlavage AR, Fleischmann RD; et al. (1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature 377 (6547 Suppl): 3–174. PMID 7566098.