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Gene Review

RAB27A  -  RAB27A, member RAS oncogene family

Homo sapiens

Synonyms: GS2, GTP-binding protein Ram, HsT18676, RAB27, RAM, ...
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Disease relevance of RAB27A


High impact information on RAB27A

  • In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not [3].
  • RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis [3].
  • We also describe the molecular organization of RAB27A and a multiplex polymerase chain reaction assay for the founder deletion in this kindred [1].
  • These data suggested that GTP hydrolysis of Rab27 was not necessary for inducing the secretion [4].
  • Moreover, the GROalpha/MCP-1-containing granules were Rab27-negative, contrasting the Rab27-positive, WPB [5].

Biological context of RAB27A

  • The RAB27A gene comprises five coding exons and two non-coding exons, of which one is alternatively used, and spans approximately 65 kb of DNA [6].
  • As with RAB27A in Griscelli Disease, RAB27B may be also associated with human disease mapping to chromosome 18 [7].
  • Our findings demonstrate extensive genetic and allelic heterogeneity in FHL and delineate an approach for functionally characterizing missense mutations in RAB27A and UNC13D [8].
  • Two different genetic forms, GS1 and GS2, respectively, account for the mutually exclusive neurological and immunological phenotypes [9].
  • Genome information suggests that other putative Rab27 effector proteins, tentatively termed as exophilins or Slp/Slac2, are predicted to exist because these proteins share the conserved N-terminal Rab27-binding domain and show Rab27-binding activity in vitro or when overexpressed in cell lines [10].

Anatomical context of RAB27A

  • Rab27a plays a pivotal role in the transport of melanosomes to dendrite tips of melanocytes and mutations in RAB27A, which impair melanosome transport cause the pigmentary dilution and the immune deficiency found in several patients with Griscelli syndrome (GS) [11].
  • Most importantly, we show that cytotoxic activity of the patient's CD8+ T lymphocytes can be rescued in vitro by RAB27A gene transfer mediated by a recombinant retroviral vector, a first step towards a potential treatment of the acute phase of GS2 by RAB27A transduced lymphocytes [12].
  • In addition, GS1 patients show primary neurological impairment, whereas GS2 patients present immunodeficiency and periods of lymphocyte proliferation and activation, leading to their infiltration in many organs, such as the nervous system, causing secondary neurological damage [12].
  • In most Griscelli patients, the RAB27A gene, which encodes a small GTPase that is associated with the melanosome membrane in melanocytes, is mutated [13].
  • Griscelli syndrome: report of the first peripheral blood stem cell transplant and the role of mutations in the RAB27A gene as an indication for BMT [14].

Associations of RAB27A with chemical compounds

  • In leaves, GS2 functions to assimilate ammonia produced by nitrate reduction and photorespiration, and GS1 is the major isoform assimilating NH3 produced by all other metabolic processes, including symbiotic N2 fixation in the nodules [15].
  • Mg2+ was the most effective activator, the highest activity of GS1 being reached at 5 mM, and that of GS2 at 20 mM MgCl2 [16].
  • As GS2 lipase has a robust activity that can affect the intracellular retinol levels, we postulated that its activity must be regulated [17].
  • Rab27 was detected in the apical plasma membrane (APM) and secretory granule membrane (SGM) fractions, and was translocated to the APM after IPR stimulation for 5min, but was detected at lower levels in the APM after 30min [18].

Other interactions of RAB27A

  • Based on these findings, I propose that SHD1 of the Slp and Slac2 families be referred to as RBD27 (Rab-binding domain specific for Rab27 isoforms) [19].
  • As recently reported, only patients with mutations of the RAB27A gene suffer from immunodeficiency and hemophagocytic lymphohistiocytosis [14].
  • Our results indicate that Slp2-a, Slp4-a/granuphilin-a and rabphilin are capable of interacting with the plasma membrane directly or indirectly, and thus that these Rab27 effectors form a bridge between Rab27-bound organelles and the plasma membrane [20].
  • CONCLUSIONS: Our results indicate that the Rab27 subfamily of Ras-like GTPases is highly conserved in mammals [7].
  • In the beta-cell line INS-1E wild-type Noc2, Noc265E, and Noc258A, a mutant capable of interacting with Rab27 but not Rab3, colocalized with insulin-containing vesicles [21].

Analytical, diagnostic and therapeutic context of RAB27A

  • Immunohistochemistry of rat retina showed that Ram/Rab27 is expressed in the pigment epithelium and choriocapillaris, the two retinal cell layers that degenerate earliest in choroideremia [2].
  • Compared with a control group, the alteration of the half-life both of NA and R-SV was less marked in GS1 than in GS2 [22].
  • The transcription of GS1-GS2 genes in the transformants was also confirmed by Northern blot analysis [23].
  • A plant constitutive expression vector p2GS harboring GS1 and GS2 under the control of rice actin 1 (Act1) and maize ubiquitin (Ubi) promoters was constructed for the first time in a single plasmid, and 3 rounds of ligation and transformation were performed [23].


  1. Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A, not MYO5A. Anikster, Y., Huizing, M., Anderson, P.D., Fitzpatrick, D.L., Klar, A., Gross-Kieselstein, E., Berkun, Y., Shazberg, G., Gahl, W.A., Hurvitz, H. Am. J. Hum. Genet. (2002) [Pubmed]
  2. Deficient geranylgeranylation of Ram/Rab27 in choroideremia. Seabra, M.C., Ho, Y.K., Anant, J.S. J. Biol. Chem. (1995) [Pubmed]
  3. Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Ménasché, G., Pastural, E., Feldmann, J., Certain, S., Ersoy, F., Dupuis, S., Wulffraat, N., Bianchi, D., Fischer, A., Le Deist, F., de Saint Basile, G. Nat. Genet. (2000) [Pubmed]
  4. Constitutive GDP/GTP Exchange and Secretion-dependent GTP Hydrolysis Activity for Rab27 in Platelets. Kondo, H., Shirakawa, R., Higashi, T., Kawato, M., Fukuda, M., Kita, T., Horiuchi, H. J. Biol. Chem. (2006) [Pubmed]
  5. Characterization of a novel chemokine-containing storage granule in endothelial cells: evidence for preferential exocytosis mediated by protein kinase A and diacylglycerol. Øynebråten, I., Barois, N., Hagelsteen, K., Johansen, F.E., Bakke, O., Haraldsen, G. J. Immunol. (2005) [Pubmed]
  6. Cloning, mapping and characterization of the human RAB27A gene. Tolmachova, T., Ramalho, J.S., Anant, J.S., Schultz, R.A., Huxley, C.M., Seabra, M.C. Gene (1999) [Pubmed]
  7. Chromosomal mapping, gene structure and characterization of the human and murine RAB27B gene. Ramalho, J.S., Tolmachova, T., Hume, A.N., McGuigan, A., Gregory-Evans, C.Y., Huxley, C., Seabra, M.C. BMC Genet. (2001) [Pubmed]
  8. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Zur Stadt, U., Beutel, K., Kolberg, S., Schneppenheim, R., Kabisch, H., Janka, G., Hennies, H.C. Hum. Mutat. (2006) [Pubmed]
  9. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). Ménasché, G., Ho, C.H., Sanal, O., Feldmann, J., Tezcan, I., Ersoy, F., Houdusse, A., Fischer, A., de Saint Basile, G. J. Clin. Invest. (2003) [Pubmed]
  10. The roles of Rab27 and its effectors in the regulated secretory pathways. Izumi, T., Gomi, H., Kasai, K., Mizutani, S., Torii, S. Cell Struct. Funct. (2003) [Pubmed]
  11. Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome. Bahadoran, P., Busca, R., Chiaverini, C., Westbroek, W., Lambert, J., Bille, K., Valony, G., Fukuda, M., Naeyaert, J.M., Ortonne, J.P., Ballotti, R. J. Biol. Chem. (2003) [Pubmed]
  12. Griscelli syndrome: characterization of a new mutation and rescue of T-cytotoxic activity by retroviral transfer of RAB27A gene. Bizario, J.C., Feldmann, J., Castro, F.A., Ménasché, G., Jacob, C.M., Cristofani, L., Casella, E.B., Voltarelli, J.C., de Saint-Basile, G., Espreafico, E.M. J. Clin. Immunol. (2004) [Pubmed]
  13. Rab27b is up-regulated in human Griscelli syndrome type II melanocytes and linked to the actin cytoskeleton via exon F-Myosin Va transcripts. Westbroek, W., Lambert, J., De Schepper, S., Kleta, R., Van Den Bossche, K., Seabra, M.C., Huizing, M., Mommaas, M., Naeyaert, J.M. Pigment Cell Res. (2004) [Pubmed]
  14. Griscelli syndrome: report of the first peripheral blood stem cell transplant and the role of mutations in the RAB27A gene as an indication for BMT. Schuster, F., Stachel, D.K., Schmid, I., Baumeister, F.A., Graubner, U.B., Weiss, M., Haas, R.J., Belohradsky, B.H. Bone Marrow Transplant. (2001) [Pubmed]
  15. Cytosolic glutamine synthetase in soybean is encoded by a multigene family, and the members are regulated in an organ-specific and developmental manner. Morey, K.J., Ortega, J.L., Sengupta-Gopalan, C. Plant Physiol. (2002) [Pubmed]
  16. Purification and partial characterization of glutamine synthetase isoforms from Triticale seedlings. Bielawski, W. Acta Biochim. Pol. (1994) [Pubmed]
  17. Molecular screening for GS2 lipase regulators: inhibition of keratinocyte retinylester hydrolysis by TIP47. Gao, J.G., Simon, M. J. Invest. Dermatol. (2006) [Pubmed]
  18. Functional involvement of Noc2, a Rab27 effector, in rat parotid acinar cells. Imai, A., Yoshie, S., Nashida, T., Shimomura, H., Fukuda, M. Arch. Biochem. Biophys. (2006) [Pubmed]
  19. Synaptotagmin-like protein (Slp) homology domain 1 of Slac2-a/melanophilin is a critical determinant of GTP-dependent specific binding to Rab27A. Fukuda, M. J. Biol. Chem. (2002) [Pubmed]
  20. Rab27 and its effectors in secretory granule exocytosis: a novel docking machinery composed of a Rab27.effector complex. Fukuda, M. Biochem. Soc. Trans. (2006) [Pubmed]
  21. The Rab-binding protein Noc2 is associated with insulin-containing secretory granules and is essential for pancreatic beta-cell exocytosis. Cheviet, S., Coppola, T., Haynes, L.P., Burgoyne, R.D., Regazzi, R. Mol. Endocrinol. (2004) [Pubmed]
  22. Impaired plasma clearance of nicotinic acid and rifamycin-SV in Gilbert's syndrome: evidence of a functional heterogeneity. Gentile, S., Marmo, R., Persico, M., Bronzino, P., Coltorti, M. Hepatogastroenterology (1985) [Pubmed]
  23. Highly effective expression of glutamine synthetase genes GS1 and GS2 in transgenic rice plants increases nitrogen-deficiency tolerance. Sun, H., Huang, Q.M., Su, J. Zhi Wu Sheng Li Yu Fen Zi Sheng Wu Xue Xue Bao (2005) [Pubmed]
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