Alternative titles; symbols
HGNC Approved Gene Symbol: RHOBTB3
Cytogenetic location: 5q15 Genomic coordinates (GRCh38): 5:95,717,624-95,796,361 (from NCBI)
Members of the RHOBTB subfamily of Rho GTPases are evolutionarily conserved. They are characterized by a modular organization, consisting of a GTPase domain, a proline-rich region, a tandem of 2 BTB (broad complex, tramtrack, and bric-a-brac) domains, and a conserved C-terminal region. The BTB domain, also known as a POZ (poxvirus and zinc finger) domain, is involved in protein-protein interactions (summary by Ramos et al., 2002).
By randomly sequencing clones from a size-fractionated brain cDNA library, Nagase et al. (1998) obtained a cDNA encoding RHOBTB3, which they called KIAA0878. The deduced protein contains 611 amino acids. RT-PCR followed by ELISA revealed high expression in ovary, moderate expression in heart, brain, liver, pancreas, and testis, and weak expression in all other tissues tested.
By searching an EST database, Ramos et al. (2002) obtained full-length cDNAs encoding RHOBTB1 (607351), RHOBTB2 (607352), and RHOBTB3. RHOBTB3 contains all of the domains characteristic of RHOBTB proteins. The C-terminal domain consists of about 80 amino acids in 4 consecutive alpha helices, with the last third having a high content of charged residues. RHOBTB3 ends in a prenylation motif not found in RHOBTB1 and RHOBTB2. RHOBTB3 shares 88% nucleotide identity with mouse Rhobtb3. Northern dot blot analysis revealed ubiquitous expression of RHOBTB3, with highest levels in placenta, testis, pancreas, adrenal and salivary gland, and neural and cardiac tissue. RHOBTB3 was also expressed in fetal tissues, particularly brain, heart, and lung. Northern blot analysis of mouse tissues revealed ubiquitous expression, with highest levels in brain, heart, and uterus.
Espinosa et al. (2009) found that RHOBTB3 bound directly to the small GTPase RAB9 (300284) and functioned with RAB9 in recycling M6PR proteins (154540) from endosomes to the trans-Golgi network. RHOBTB3 bound and hydrolyzed ATP rather than GTP, and binding to RAB9 opened the autoinhibited RHOBTB3 protein to permit maximal ATP hydrolysis. Because RHOBTB3 interacted with the cargo selection protein TIP47 (M6PRBP1; 602702) on membranes, Espinosa et al. (2009) proposed that RHOBTB3 may remove TIP47 from vesicles to permit their efficient docking and fusion at the Golgi.
Ramos et al. (2002) determined that the RHOBTB3 gene contains 12 exons and spans about 66 kb.
By genomic sequence analysis, Ramos et al. (2002) mapped the RHOBTB3 gene to chromosome 5q14.3, upstream of the PCSK1 gene (162150).
Espinosa, E. J., Calero, M., Sridevi, K., Pfeffer, S. R. RhoBTB3: a Rho GTPase-family ATPase required for endosome to Golgi transport. Cell 137: 938-948, 2009. [PubMed: 19490898] [Full Text: https://doi.org/10.1016/j.cell.2009.03.043]
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 5: 355-364, 1998. [PubMed: 10048485] [Full Text: https://doi.org/10.1093/dnares/5.6.355]
Ramos, S., Khademi, F., Somesh, B. P., Rivero, F. Genomic organization and expression profile of the small GTPases of the RhoBTB family in human and mouse. Gene 298: 147-157, 2002. [PubMed: 12426103] [Full Text: https://doi.org/10.1016/s0378-1119(02)00980-0]