Alternative titles; symbols
HGNC Approved Gene Symbol: NUB1
Cytogenetic location: 7q36.1 Genomic coordinates (GRCh38): 7:151,341,812-151,378,449 (from NCBI)
NUB1 interacts with and negatively regulates NEDD8 (603171), a ubiquitin-like protein that covalently conjugates to cullin (see 603134) family members.
Using NEDD8 as bait in a yeast 2-hybrid screen, Kito et al. (2001) cloned NUB1. The deduced 601-amino acid protein has a calculated molecular mass of about 69 kD. The N-terminal half of NUB1 contains 2 coiled-coil domains, and the C-terminal half contains 2 ubiquitin-associated domains, which are separated by a bipartite nuclear localization signal, followed by a PEST sequence. Northern blot analysis detected strong expression of a 2.3-kb transcript in testis and weak expression of a 3.5-kb transcript in testis, ovary, heart, and skeletal muscle. Little to no expression was detected in other tissues. Western blot analysis detected NUB1 at an apparent molecular mass of 69 kD expressed in all cell lines tested, with variable expression between cell lines. In situ hybridization of whole mouse embryos found strongest expression in day 7 embryos and weaker expression at days 11, 15, and 17. In mouse embryos, a 3.0-kb transcript was predominant, followed by 2.5- and 2.0-kb transcripts.
Kito et al. (2001) found that interferon-beta (see 147640) induced NUB1 protein expression in HeLa and embryonic kidney cells, but not in an osteosarcoma cell line. Induction in HeLa cells was dose and time dependent. Northern blot analysis detected induction of NUB1 mRNA in HeLa cells. By yeast 2-hybrid assay, Kito et al. (2001) confirmed direct interaction between NUB1 and NEDD8, and coexpression in COS cells resulted in reduced expression of NEDD8 monomer and its conjugates. Overexpression of NUB1 did not affect the level of NEDD8 message, suggesting that NUB1 inhibits NEDD8 expression posttranscriptionally. Overexpression of NUB1 also had a profound growth-inhibitory effect on an osteosarcoma cell line.
Mutations in the aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1; 604392) gene have been found in patients with Leber congenital amaurosis (LCA1; 204000), a severe, early-onset form of retinal degeneration. Akey et al. (2002) performed a yeast 2-hybrid screen to identify AIPL1-interacting proteins in the retina. One of the identified interacting proteins corresponded to NUB1. The AIPL1-NUB1 interaction was verified by coimmunoprecipitation studies in retinoblastoma cells, demonstrating that this interaction occurred within cells that share a number of features with retinal progenitor cells. In situ hybridization studies showed that both AIPL1 and NUB1 are expressed in the developing and adult retina. The authors hypothesized that the early-onset form of retinal degeneration seen in LCA patients with AIPL1 mutations may be due to a defect in NUB1 regulation of cell cycle progression during photoreceptor maturation.
The International Radiation Hybrid Mapping Consortium mapped the NUB1 gene to chromosome 7 (sts-F17912).
Akey, D. T., Zhu, X., Dyer, M., Li, A., Sorensen, A., Blackshaw,S., Fukuda-Kamitani, T., Daiger, S. P., Craft, C. M., Kamitani, T., Sohocki, M. M. The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1. Hum. Molec. Genet. 11: 2723-2733, 2002. Note: Erratum: Hum. Molec. Genet. 12: 451 only, 2003. [PubMed: 12374762] [Full Text: https://doi.org/10.1093/hmg/11.22.2723]
Kito, K., Yeh, E. T. H., Kamitani, T. NUB1, a NEDD8-interacting protein, is induced by interferon and down-regulates the NEDD8 expression. J. Biol. Chem. 276: 20603-20609, 2001. [PubMed: 11259415] [Full Text: https://doi.org/10.1074/jbc.M100920200]