Alternative titles; symbols
HGNC Approved Gene Symbol: UNC79
Cytogenetic location: 14q32.12 Genomic coordinates (GRCh38): 14:93,333,182-93,707,876 (from NCBI)
UNC79 functions as an accessory subunit of the NALCN (611549) channel that is responsible for Na(+) leak currents. UNC79 helps to confer sensitivity of the channel to extracellular Ca(2+) concentration (Lu et al., 2010).
By sequencing clones obtained from a size-fractionated human fetal brain cDNA library, Nagase et al. (2000) cloned UNC79, which they designated KIAA1409. The deduced protein contains 1,597 amino acids. RT-PCR ELISA detected KIAA1409 expression in adult and fetal brain, adult spinal cord, and in all specific adult brain regions examined. Very weak expression was detected in pancreas, with little to no expression detected in other adult and fetal tissues.
In mouse brain, Lu et al. (2010) found that immunoprecipitation of Unc79 also precipitated Unc80 (612636) and Nalcn. Use of Nalcn -/- and Unc79 -/- mouse hippocampal neurons (see ANIMAL MODEL) and transfection in human cell lines revealed that both Nalcn and Unc79 interact directly with Unc80, but not with each other. Leak currents generated by Nalcn alone were insensitive to extracellular Ca(2+), and Unc80 provided Ca(2+) sensitivity. Unc79 appeared to contribute to Ca(2+) sensitivity of Nalcn currents by interacting with Unc80 and stabilizing Unc80 protein level. Inhibition of a Ca(2+)-sensitive G protein, possibly Casr (601199), countered Ca(2+) sensitivity of Nalcn currents.
By radiation hybrid analysis, Nagase et al. (2000) mapped the UNC79 gene to chromosome 14. Hartz (2016) mapped the UNC79 gene to chromosome 14q32.12 based on an alignment of the UNC79 sequence (GenBank AB037830) with the genomic sequence (GRCh38).
Speca et al. (2010) reported that the mouse Unc79 gene maps to chromosome 12D2.
Lu et al. (2010) stated that Unc79 -/- mice have disrupted breathing rhythms, fail to nurse, and die within the first days of life. They found that Unc79 -/- hippocampal neurons showed normal Nalcn-dependent Na+ leak currents, but their leak currents were largely insensitive to changes in extracellular Ca(2+) concentration. Overexpression of Unc80 could bypass the requirement for Unc79 and rescue extracellular Ca(2+) sensitivity. Lu et al. (2010) concluded that extracellular Ca(2+) sensitivity of Nalcn leak currents is dependent upon Unc80, but that Unc79 may contribute to Ca(2+) sensitivity, possibly by stabilizing Unc80 protein levels.
Speca et al. (2010) identified a strain of mice generated by N-ethyl-N-nitrosourea mutagenesis that showed reduced body weight in the heterozygous state. Homozygous mutants died shortly after birth. Speca et al. (2010) determined that the mutation, called 'Lightweight' (Lwt), consists of a premature stop codon in the middle of the Unc79 protein. Lwt/+ mice were modestly hyperactive and accumulated less fat than wildtype littermates. Lwt/+ mice showed increased ethanol preference and consumption compared with wildtype, and they showed strain-dependent increased food and water intake and preference for saccharin. Lwt/+ mice were resistant to isofluran but no to other anesthetic agents tested.
Hartz, P. A. Personal Communication. Baltimore, Md. 3/29/2016.
Lu, B., Zhang, Q., Wang, H., Wang, Y., Nakayama, M., Ren, D. Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex. Neuron 68: 488-499, 2010. [PubMed: 21040849] [Full Text: https://doi.org/10.1016/j.neuron.2010.09.014]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 65-73, 2000. [PubMed: 10718198] [Full Text: https://doi.org/10.1093/dnares/7.1.65]
Speca, D. J., Chihara, D., Ashique, A. M., Bowers, M. S., Pierce-Shimomura, J. T., Lee, J., Rabbee, N., Speed, T. P., Gularte, R. J., Chitwood, J., Medrano, J. F., Liao, M., Sonner, J. M., Eger, E. I., II, Peterson, A. S., McIntire, S. L. Conserved role of unc-79 in ethanol responses in lightweight mutant mice. PLOS Genet. 6: e1001057, 2010. Note: Electronic Article. [PubMed: 20714347] [Full Text: https://doi.org/10.1371/journal.pgen.1001057]