Alternative titles; symbols
HGNC Approved Gene Symbol: RANBP9
Cytogenetic location: 6p23 Genomic coordinates (GRCh38) : 6:13,621,498-13,711,835 (from NCBI)
With the 2-hybrid method using human RAN (601179) as bait, Nakamura et al. (1998) isolated a novel human protein with a molecular mass of 55 kD, which they called RANBPM. The cDNA is 2.8 kb in length and encodes a protein of 500 amino acid residues. Mouse, hamster, and human RANBPM are identical. The C-terminal half of the S. cerevisiae gene YGL227w is 30% identical to RANBPM. Immunoblotting analysis using antibodies against RANBPM revealed that RANBPM was localized within the centrosome throughout the cell cycle. Overexpression of RANBPM produced multiple spots which were colocalized with gamma-tubulin (191135) and acted as ectopic microtubule nucleation sites, resulting in a reorganization of the microtubule network. RANBPM cosedimented with centrosomal fractions by sucrose-density gradient centrifugation. Microtubule aster formation was inhibited by both anti-RANBPM antibodies and nonhydrolyzable RAN-GTP (see 602362). RANBPM specifically interacted with RAN-GTP in a 2-hybrid assay. RANBPM is localized within the central part of microtubule asters. Nakamura et al. (1998) demonstrated that RANBPM is involved in microtubule nucleation, and suggested that RAN regulates the centrosome through RANBPM.
Nishitani et al. (2001) determined that the 55-kD RANBP9 is a truncated protein. They cloned the full-length RANBP9 cDNA by PCR from a HeLa cell library and found that it encodes a deduced 729-amino acid protein with a calculated molecular mass of 79 kD. RANBP9 contains long stretches of proline within the N terminus, and a glutamine stretch following the first proline stretch. Human and mouse RANBP9 share greater than 96% sequence identity. Western blot analysis of transfected cells revealed a protein with an apparent molecular mass of 90 kD. Unlike the truncated protein, the full-length protein does not show localization within centrosomes, but localizes within the perinuclear region or the nucleus. In mitotic COS-7 cells transfected with RANBP9, fluorescence was observed throughout the cell.
By immunoprecipitation and gel filtration of HeLa cell extracts, Nishitani et al. (2001) detected RANBP9 at 90 kD within a protein complex of more than 670 kD. Contrary to earlier suggestions, very little RAN was detected in these complexes. Anti-RANBP9 did not inhibit microtubule assembly.
Using yeast 2-hybrid analysis, Umeda et al. (2003) showed that N-terminally truncated RANBPM interacted with TWA1 (611625), MPHOSPH8 (611626), and muskelin (MKLN1; 605623). Coimmunoprecipitation and gel filtration analyses demonstrated that endogenous Ranbpm and Twa1 interacted in COS-7 cells, and both proteins interacted with GST-fused human muskelin in a 670-kD protein complex in transfected COS-7 cells.
Using protein pull-down and coimmunoprecipitation analyses, Wang et al. (2004) showed that, like RANBP9, RANBP10 (614031) interacted directly with RAN and MET (164860), a receptor protein tyrosine kinase for hepatocyte growth factor (HGF; 142409). Pull-down experiments revealed that RANBP9 and RANBP10 competed for MET binding. RANBP9, but not RANBP10, induced ERK (MAPK3; 601795) phosphorylation and expression from a serum response element (SRE) reporter gene. RANBP10 inhibited RANBP9-mediated reporter gene activation.
Harada et al. (2008) showed that both RANBP9 and RANBP10 enhanced dihydrotestosterone (DHT)-induced transactivation activity of androgen receptor (AR; 313700). Simultaneous overexpression of RANBP10 and RANBP9 had an additive effect on AR transactivation. Both RANBP10 and RANBP9 enhanced glucocorticoid receptor (GCCR; 138040) transactivation in the presence of dexamethasone, but neither affected 17-beta-estradiol-induced transactivation of estrogen receptor (ESR1; 133430). Immunoprecipitation analysis revealed that RANBP10 complexed with androgen receptor in the presence of DHT. Furthermore, RANBP10 dimerized with itself and with RANBP9.
Nishitani et al. (2001) mapped RANBP9 to chromosome 6p23 based on sequence similarity between RANBP9 and a genomic clone (GenBank 503G16) mapped to that region.
Harada, N., Yokoyama, T., Yamaji, R., Nakano, Y., Inui, H. RanBP10 acts as a novel coactivator for the androgen receptor. Biochem. Biophys. Res. Commun. 368: 121-125, 2008. [PubMed: 18222118] [Full Text: https://doi.org/10.1016/j.bbrc.2008.01.072]
Nakamura, M., Masuda, H., Horii, J., Kuma, K., Yokoyama, N., Ohba, T., Nishitani, H., Miyata, T., Tanaka, M., Nishimoto, T. When overexpressed, a novel centrosomal protein, RanBPM, causes ectopic microtubule nucleation similar to gamma-tubulin. J. Cell Biol. 143: 1041-1052, 1998. [PubMed: 9817760] [Full Text: https://doi.org/10.1083/jcb.143.4.1041]
Nishitani, H., Hirose, E., Uchimura, Y., Nakamura, M., Umeda, M., Nishii, K., Mori, N., Nishimoto, T. Full-sized RanBPM cDNA encodes a protein possessing a long stretch of proline and glutamine within the N-terminal region, comprising a large protein complex. Gene 272: 25-33, 2001. [PubMed: 11470507] [Full Text: https://doi.org/10.1016/s0378-1119(01)00553-4]
Umeda, M., Nishitani, H., Nishimoto, T. A novel nuclear protein, Twa1, and Muskelin comprise a complex with RanBPM. Gene 303: 47-54, 2003. [PubMed: 12559565] [Full Text: https://doi.org/10.1016/s0378-1119(02)01153-8]
Wang, D., Li, Z., Schoen, S. R., Messing, E. M., Wu, G. A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling. Biochem. Biophys. Res. Commun. 313: 320-326, 2004. [PubMed: 14684163] [Full Text: https://doi.org/10.1016/j.bbrc.2003.11.124]