Alternative titles; symbols
HGNC Approved Gene Symbol: RALB
Cytogenetic location: 2q14.2 Genomic coordinates (GRCh38): 2:120,240,070-120,294,710 (from NCBI)
The human RAL proteins share more than 50% homology and some properties with the RAS proteins. Hsieh et al. (1990) isolated a member of the RAL family, RALB, a GTP-binding protein.
Using a simian Rala (179550) cDNA probe and moderate hybridization stringency, Chardin and Tavitian (1989) cloned RALA and RALB from a human pheochromocytoma library. The deduced 206-amino acid RALB protein shares about 85% identity with RALA.
The exocyst is an evolutionarily conserved octameric complex involved in post-Golgi targeting of secretory vesicles. Moskalenko et al. (2003) noted that RAL GTPases regulate exocyst-dependent trafficking and are required for exocyst assembly. Using yeast 2-hybrid analysis of HEK293T cells, they showed that human EXO84 (EXOC8; 615283) interacted with RALA (179550) and RALB, but not with any other small GTPase examined. RALA and RALB interacted with EXO84 and SEC5 (EXOC2; 615329), but not with any other exocyst component examined. In vitro binding assays revealed that EXO84 interacted with GTP-bound RALA, and truncation analysis revealed that the pleckstrin (PLEK; 173570) homology (PH) domain of EXO84 was required for the interaction. Membrane depolarization resulted in recruitment of the isolated RAL-binding domain of EXO84 to membranes, and this recruitment required lipid-binding prenylated RALB. RAL-GTP competed with phosphatidylinositol 3,4,5-trisphosphate for EXO84 binding. In rat PC12 cells, Exo84 appeared to fractionate with a subcomplex of vesicles that included Sec10 (EXOC5; 604469), but not Sec5. Moskalenko et al. (2003) proposed that RAL GTPases regulate assembly of the full exocyst complex through interaction with EXO84 and SEC5.
Using normal and tumorigenic human epithelial cell lines, Chien et al. (2006) found that a RALB/SEC5 effector complex specifically supported tumor cell survival by directly recruiting and activating TBK1 (604834). In cancer cell lines, constitutive engagement of this pathway, via chronic RALB activation, restricted initiation of apoptotic programs typically engaged in the context of oncogenic stress. Although dispensable for survival of nontumorigenic human epithelial cells in culture, this pathway helped mount an innate immune response to double-stranded RNA or Sendai virus exposure. Chien et al. (2006) concluded that the RALB/SEC5 effector complex is a component of TBK1-dependent innate immune signaling and that this pathway is required to support pathologic survival in the context of a tumorigenic regulatory environment.
By study of human/Chinese hamster hybrids, Hsieh et al. (1990) concluded that the RALB gene maps to chromosome 2cen-q13.
Chardin, P., Tavitian, R. Coding sequences of human ralA and ralB cDNAs. Nucleic Acids Res. 17: 4380 only, 1989. [PubMed: 2662142] [Full Text: https://doi.org/10.1093/nar/17.11.4380]
Chien, Y., Kim, S., Bumeister, R., Loo, Y.-M., Kwon, S. W., Johnson, C. L., Balakireva, M. G., Romeo, Y., Kopelovich, L., Gale, M., Jr., Yeaman, C., Camonis, J. H., Zhao, Y., White, M. A. RalB GTPase-mediated activation of the I-kappa-B family kinase TBK1 couples innate immune signaling to tumor cell survival. Cell 127: 157-170, 2006. [PubMed: 17018283] [Full Text: https://doi.org/10.1016/j.cell.2006.08.034]
Hsieh, C.-L., Swaroop, A., Francke, U. Chromosomal localization and cDNA sequence of human RALB, a GTP binding protein. Somat. Cell Molec. Genet. 16: 407-410, 1990. [PubMed: 2120779] [Full Text: https://doi.org/10.1007/BF01232469]
Moskalenko, S., Tong, C., Rosse, C., Mirey, G., Formstecher, E., Daviet, L., Camonis, J., White, M. A. Ral GTPases regulate exocyst assembly through dual subunit interactions. J. Biol. Chem. 278: 51743-51748, 2003. [PubMed: 14525976] [Full Text: https://doi.org/10.1074/jbc.M308702200]