GAPVD1

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.[5][6]

GAPVD1
Identifiers
Aliases	GAPVD1, GAPEX5, GAPex-5, RAP6, GTPase activating protein and VPS9 domains 1
External IDs	OMIM: 611714 MGI: 1913941 HomoloGene: 32637 GeneCards: GAPVD1
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q33.3 Start 125,261,794 bp[1] End 125,367,207 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 B Start 34,674,594 bp[2] End 34,755,232 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GTPase activating protein binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity • guanyl-nucleotide exchange factor activity • Rab guanyl-nucleotide exchange factor activity • cadherin binding • GO:0001948 protein binding Cellular component • endosome • membrane • cytosol Biological process • GO:0043087, GO:0032313, GO:0032319, GO:0032314, GO:0043088 regulation of GTPase activity • endocytosis • regulation of protein transport • signal transduction • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • membrane organization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	26130	66691
Ensembl	ENSG00000165219	ENSMUSG00000026867
UniProt	Q14C86	Q6PAR5
RefSeq (mRNA)	NM_001282679 NM_001282680 NM_001282681 NM_015635 NM_001330777 NM_001330778 NM_001354293 NM_001354294 NM_001354295 NM_001354296 NM_001354297 NM_001354298 NM_001354299 NM_001354300 NM_001354301	NM_025709 NM_001356441
RefSeq (protein)	NP_001269608 NP_001269609 NP_001269610 NP_001317706 NP_001317707 NP_056450 NP_001341222 NP_001341223 NP_001341224 NP_001341225 NP_001341226 NP_001341227 NP_001341228 NP_001341229 NP_001341230	NP_079985 NP_001343370
Location (UCSC)	Chr 9: 125.26 – 125.37 Mb	Chr 2: 34.67 – 34.76 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

GAPVD1 is Rab GTPase guanine nucleotide exchange factor essential for activation of RAB5A during engulfment of apoptotic cells.[7] GAPVD1 is also involved in the degradation of the epidermal growth factor receptor.[8] Gapex-5 mediated activation of Rab5 has been implicated in the insulin stimulated formation of plasma membrane phosphatidylinositol-3-phosphate.[9]

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[10] and Rab31.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000165219 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026867 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: GAPVD1 GTPase activating protein and VPS9 domains 1".
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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. S2CID 2371325.
• 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.