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Gene Review

RAB6A  -  RAB6A, member RAS oncogene family

Homo sapiens

Synonyms: RAB6, Rab-6, Ras-related protein Rab-6A
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Disease relevance of RAB6A

  • A new Rab6 homolog cDNA, Rab6c, was discovered by a hypermethylated DNA fragment probe that was isolated from a human multidrug resistant (MDR) breast cancer cell line, MCF7/AdrR, by the methylation sensitive-representational difference analysis (MS-RDA) technique [1].
  • Characterization of the unprocessed and processed forms of rab6 expressed in baculovirus/insect cell systems [2].

High impact information on RAB6A


Biological context of RAB6A

  • Identification of small GTP-binding rab proteins in human platelets: thrombin-induced phosphorylation of rab3B, rab6, and rab8 proteins [8].
  • The importance of geranylgeranylation to the interaction of Rab proteins with RabGDI was investigated with a set of Rab6 mutants post-translationally modified by all known C-terminal lipid combinations [9].
  • The methylation status of the CXC motif did not significantly affect interaction of wild type Rab6 with RabGDI [9].
  • Moreover, we used small interfering RNA mediated down-regulation of rab6A and A' expression and found that reduced levels of rab6 perturbs organization of the Golgi apparatus and delays Golgi-to-ER recycling [10].
  • Analysis of the human Rab6A gene structure reveals the presence of a duplicated exon, and incorporation of either of the two exons by alternative splicing is shown to generate two Rab6 isoforms named Rab6A and Rab6A', which differ in only three amino acid residues located in regions flanking the PM3 GTP-binding domain of the proteins [11].

Anatomical context of RAB6A

  • Whereas rab3B protein was found to be mainly cytosolic, rab6 and rab8 proteins were preferentially targeted to the plasma membrane and to the alpha granules [8].
  • These findings provide evidence that members of the subfamily of rab proteins, rab6 and rab8, are localized in platelets to one type of specific secretory vesicle, the alpha granule, and would suggest their possible implication in the secretion process through phosphorylation mechanisms [8].
  • The two isoforms of the Rab6 GTPase, Rab6A and Rab6A', regulate a retrograde transport route connecting early endosomes and the endoplasmic reticulum via the Golgi complex in interphasic cells [12].
  • To test the role of these elements experimentally, we transplanted them onto rab6, which is associated with the Golgi complex [13].
  • First, we found that the C-terminus of rab5 could target rab6 to the plasma membrane and early endosomes but it did not confer rab5-like stimulation of endocytosis [13].

Associations of RAB6A with chemical compounds

  • The activation of platelets by thrombin, a potent inducer of secretion, resulted in the phosphorylation of rab3B, rab6, and rab8 proteins, whereas no phosphorylation was observed in the presence of prostaglandin E1, which stimulates cAMP-dependent protein kinase and inhibits the secretion process [8].
  • Recombinant antibodies specific to the guanosine triphosphate (GTP)-bound conformation of the small guanosine triphosphatase (GTPase) Rab6, a regulator of membrane traffic, were generated and used to locate Rab6.GTP in fixed cells, and, after green fluorescent protein (GFP) tagging and intracellular expression, to follow Rab6.GTP in vivo [14].
  • Analogous mutations in rab3a, rab5, rab6, and H-ras did not inhibit processing of VSV-G to the complex, sialic acid containing form diagnostic of transport to the trans Golgi compartment [15].
  • Remarkably, rab6 Q72L effects, which require the integrity of microtubules, were almost indistinguishable from those induced by brefeldin A, a fungic metabolite that causes a mixing of Golgi and ER membranes [16].
  • The distribution of rab6 across sucrose density gradient fractions parallels the distribution of sialyltransferase (a TGN marker) activity [17].

Physical interactions of RAB6A

  • Rab6 was in its GTP-bound conformation on the Golgi apparatus and transport intermediates, and the geometry of transport intermediates was modulated by Rab6 activity [14].

Regulatory relationships of RAB6A

  • The Rab6 GTPase regulates intracellular transport at the level of the Golgi apparatus, probably in a retrograde direction [18].

Other interactions of RAB6A

  • In the current studies, we produced REP-1 and REP-2 by recombinant DNA methods and showed that both proteins were approximately equal in facilitating the attachment of GG groups to several Rab proteins, including Rab1A, Rab5A, and Rab6 [19].
  • A similar binding was seen to rab1 but not to rab6, both Golgi rabs [20].
  • Interestingly, however, loop3/beta 3 of Rab6 when introduced into H-Ras is sufficient to allow some in vivo processing of a C-terminal CSC motif [9].
  • The Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis [21].
  • Nevertheless, we consider the WTH3 gene a new member of the Rab6 gene family [22].

Analytical, diagnostic and therapeutic context of RAB6A

  • By immunolabelling and electron microscopy, Rab6p appears to be concentrated predominantly on the medial and trans cisternae and distributed over their entire surface [3].
  • A confocal laser scanning microscopic (CLSM) approach coupled with image analysis was used to compare the localization of rab6p with selected reference Golgi markers by double immunofluorescence on culture cell lines [23].
  • By confocal and EM immunocytochemistry it can be seen that most of rab6 is associated with the photoreceptor trans-Golgi cisternae, trans-Golgi network (TGN) and post-Golgi vesicles [17].
  • Four GTP-binding proteins were identified by 2-D gel immunoblotting and these correspond to rap1 and 2 and two forms of rab6. ras-Proteins are most likely present in the [alpha 32P]GTP 2-D gel blots but their levels may be too low to be detected by immunoblotting [24].
  • Confocal microscopy reveals that calpain II colocalizes with the subcellular proteins calnexin and Rab6 in cells bound to laminin [25].


  1. Rab6c, a new member of the rab gene family, is involved in drug resistance in MCF7/AdrR cells. Shan, J., Mason, J.M., Yuan, L., Barcia, M., Porti, D., Calabro, A., Budman, D., Vinciguerra, V., Xu, H. Gene (2000) [Pubmed]
  2. Characterization of the unprocessed and processed forms of rab6 expressed in baculovirus/insect cell systems. Yang, C., Mayau, V., Godeau, F., Goud, B. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  3. Small GTP-binding protein associated with Golgi cisternae. Goud, B., Zahraoui, A., Tavitian, A., Saraste, J. Nature (1990) [Pubmed]
  4. Golgins in the structure and dynamics of the Golgi apparatus. Barr, F.A., Short, B. Curr. Opin. Cell Biol. (2003) [Pubmed]
  5. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Matanis, T., Akhmanova, A., Wulf, P., Del Nery, E., Weide, T., Stepanova, T., Galjart, N., Grosveld, F., Goud, B., De Zeeuw, C.I., Barnekow, A., Hoogenraad, C.C. Nat. Cell Biol. (2002) [Pubmed]
  6. Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum. Girod, A., Storrie, B., Simpson, J.C., Johannes, L., Goud, B., Roberts, L.M., Lord, J.M., Nilsson, T., Pepperkok, R. Nat. Cell Biol. (1999) [Pubmed]
  7. Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. Hyvola, N., Diao, A., McKenzie, E., Skippen, A., Cockcroft, S., Lowe, M. EMBO J. (2006) [Pubmed]
  8. Identification of small GTP-binding rab proteins in human platelets: thrombin-induced phosphorylation of rab3B, rab6, and rab8 proteins. Karniguian, A., Zahraoui, A., Tavitian, A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. Determination of structural requirements for the interaction of Rab6 with RabGDI and Rab geranylgeranyltransferase. Beranger, F., Cadwallader, K., Porfiri, E., Powers, S., Evans, T., de Gunzburg, J., Hancock, J.F. J. Biol. Chem. (1994) [Pubmed]
  10. Regulation of microtubule-dependent recycling at the trans-Golgi network by Rab6A and Rab6A'. Young, J., Stauber, T., del Nery, E., Vernos, I., Pepperkok, R., Nilsson, T. Mol. Biol. Cell (2005) [Pubmed]
  11. Alternative splicing of the human Rab6A gene generates two close but functionally different isoforms. Echard, A., Opdam, F.J., de Leeuw, H.J., Jollivet, F., Savelkoul, P., Hendriks, W., Voorberg, J., Goud, B., Fransen, J.A. Mol. Biol. Cell (2000) [Pubmed]
  12. A role for the Rab6A' GTPase in the inactivation of the Mad2-spindle checkpoint. Miserey-Lenkei, S., Couëdel-Courteille, A., Del Nery, E., Bardin, S., Piel, M., Racine, V., Sibarita, J.B., Perez, F., Bornens, M., Goud, B. EMBO J. (2006) [Pubmed]
  13. Distinct structural elements of rab5 define its functional specificity. Stenmark, H., Valencia, A., Martinez, O., Ullrich, O., Goud, B., Zerial, M. EMBO J. (1994) [Pubmed]
  14. Recombinant antibodies to the small GTPase Rab6 as conformation sensors. Nizak, C., Monier, S., del Nery, E., Moutel, S., Goud, B., Perez, F. Science (2003) [Pubmed]
  15. GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex. Tisdale, E.J., Bourne, J.R., Khosravi-Far, R., Der, C.J., Balch, W.E. J. Cell Biol. (1992) [Pubmed]
  16. GTP-bound forms of rab6 induce the redistribution of Golgi proteins into the endoplasmic reticulum. Martinez, O., Antony, C., Pehau-Arnaudet, G., Berger, E.G., Salamero, J., Goud, B. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  17. Rab6 is associated with a compartment that transports rhodopsin from the trans-Golgi to the site of rod outer segment disk formation in frog retinal photoreceptors. Deretic, D., Papermaster, D.S. J. Cell. Sci. (1993) [Pubmed]
  18. Characterization of GAPCenA, a GTPase activating protein for Rab6, part of which associates with the centrosome. Cuif, M.H., Possmayer, F., Zander, H., Bordes, N., Jollivet, F., Couedel-Courteille, A., Janoueix-Lerosey, I., Langsley, G., Bornens, M., Goud, B. EMBO J. (1999) [Pubmed]
  19. REP-2, a Rab escort protein encoded by the choroideremia-like gene. Cremers, F.P., Armstrong, S.A., Seabra, M.C., Brown, M.S., Goldstein, J.L. J. Biol. Chem. (1994) [Pubmed]
  20. Identification of rabaptin-5, rabex-5, and GM130 as putative effectors of rab33b, a regulator of retrograde traffic between the Golgi apparatus and ER. Valsdottir, R., Hashimoto, H., Ashman, K., Koda, T., Storrie, B., Nilsson, T. FEBS Lett. (2001) [Pubmed]
  21. The Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis. Hill, E., Clarke, M., Barr, F.A. EMBO J. (2000) [Pubmed]
  22. WTH3, a new member of the Rab6 gene family, and multidrug resistance. Shan, J., Yuan, L., Budman, D.R., Xu, H.P. Biochim. Biophys. Acta (2002) [Pubmed]
  23. The small GTP-binding protein rab6p is distributed from medial Golgi to the trans-Golgi network as determined by a confocal microscopic approach. Antony, C., Cibert, C., Géraud, G., Santa Maria, A., Maro, B., Mayau, V., Goud, B. J. Cell. Sci. (1992) [Pubmed]
  24. Several small GTP-binding proteins are strongly down-regulated in simian virus 40 (SV40) transformed human keratinocytes and may be required for the maintenance of the normal phenotype. Gromov, P.S., Celis, J.E. Electrophoresis (1994) [Pubmed]
  25. Association of the calpain/calpastatin network with subcellular organelles. Hood, J.L., Logan, B.B., Sinai, A.P., Brooks, W.H., Roszman, T.L. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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