Alternative titles; symbols
HGNC Approved Gene Symbol: GNL2
Cytogenetic location: 1p34.3 Genomic coordinates (GRCh38) : 1:37,566,816-37,595,937 (from NCBI)
By screening a primary ductal breast carcinoma cDNA expression library with autologous patient serum, followed by 5-prime and 3-prime RACE, Racevskis et al. (1996) cloned GNL2, which they called NGP1. The deduced 731-amino acid protein has a calculated molecular mass of 83.7 kD. GNL2 contains 3 GTP-binding protein motifs, 2 potential N-glycosylation sites, and a nuclear localization signal. Northern blot analysis detected a transcript of 2.3 kb highly expressed in testis, followed by skeletal muscle. All other normal tissues and breast tumors examined showed lower expression. Immunohistochemical analysis localized NGP1 to the nucleolus and nucleolar organizer region of all cell types analyzed. Southern blot analysis indicated that NGP1 is conserved in chicken and all mammalian species tested.
The International Radiation Hybrid Mapping Consortium mapped the GNL2 gene to chromosome 1 (RH71352).
Matsuo et al. (2014) showed that a conserved S. cerevisiae GTPase Nug2 (orthologous to human GNL2) has a key role in the timing of nuclear export competence. Nug2 binds the intersubunit face of maturing, nucleoplasmic pre-60S particles, and the location clashes with the position of Nmd3 (611021), a key pre-60S export adaptor. Nug2 and Nmd3 are not present on the same pre-60S particles, with Nug2 binding before Nmd3. Depletion of Nug2 causes premature Nmd3 binding to the pre-60S particles, whereas mutations in the G domain of Nug2 block Nmd3 recruitment, resulting in severe 60S export defects. Two pre-60S remodeling factors, the Rea1 ATPase and its cosubstrate Rsa4, are present on Nug2-associated particles, and both show synthetic lethal interactions with Nug2 mutants. Release of Nug2 from pre-60S particles requires both its potassium-dependent GTPase activity and the remodeling ATPase activity of Rea1. Matsuo et al. (2014) concluded that Nug2 is a regulatory GTPase that monitors pre-60S maturation, with release from its placeholder site linked to recruitment of the nuclear export machinery.
Matsuo, Y., Granneman, S., Thoms, M., Manikas, R.-G., Tollervey, D., Hurt, E. Coupled GTPase and remodelling ATPase activities form a checkpoint for ribosome export. Nature 505: 112-116, 2014. [PubMed: 24240281] [Full Text: https://doi.org/10.1038/nature12731]
Racevskis, J., Dill, A., Stockert, R., Fineberg, S. A. Cloning of a novel nucleolar guanosine 5-prime-triphosphate binding protein autoantigen from a breast tumor. Cell Growth Diff. 7: 271-280, 1996. [PubMed: 8822211]