Ras-related protein Ral-B (RALB)
The protein contains 206 amino acids for an estimated molecular weight of 23409 Da.
Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking (PubMed:10393179, PubMed:17875936, PubMed:18756269). Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles (By similarity). Required both to stabilize the assembly of the exocyst complex and to localize functional exocyst complexes to the leading edge of migrating cells (By similarity). Required for suppression of apoptosis (PubMed:17875936). In late stages of cytokinesis, upon completion of the bridge formation between dividing cells, mediates exocyst recruitment to the midbody to drive abscission (PubMed:18756269). Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors (PubMed:10393179). (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Apoptotic process
Cell cycle
Cell division
Cellular response to exogenous dsRNA
Cellular response to starvation
Cytokinesis
Metabolic process
Negative regulation of protein binding
Neurotrophin TRK receptor signaling pathway
Positive regulation of autophagosome assembly
Positive regulation of protein binding
Positive regulation of protein phosphorylation
Positive regulation of protein serine/threonine kinase activity
Ras protein signal transduction
Regulation of exocyst assembly
Regulation of exocyst localization
Signal transduction
The reference OMIM entry for this protein is 179551
V-ral simian leukemia viral oncogene homolog b; ralb
Ras-like protein b
CLONING
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.GENE FUNCTION
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.MAPPING
By study of human/Chinese hamster hybrids, Hsieh et al. (1990) concluded that the RALB gene maps to chromosome 2cen-q13. ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 179551 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed