Alternative titles; symbols
HGNC Approved Gene Symbol: RUFY3
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:70,703,767-70,808,619 (from NCBI)
By randomly sequencing clones from a size-fractionated brain cDNA library, Nagase et al. (1998) obtained a cDNA encoding RUFY3, which they called KIAA0871, encoding a deduced 469-amino acid protein.
Using 2-dimensional electrophoresis analysis of proteins in stage 2 and stage 3 hippocampal neurons, Mori et al. (2007) identified RUFY3, which they called single axon-related-1 (singar1), in human, mouse, and rat. The deduced proteins in all 3 species have 469 amino acids and contain a RUN domain. The mouse and rat proteins contain a splice variant, designated singar2, of 487 amino acids. Expression of singar1 in rat brain was relatively low on embryonic day 15, peaked around postnatal day 4, and decreased in the adult brain. Immunocytochemical analysis showed that rat singar1 and singar2 accumulate in growth cones of minor processes and axons.
Mori et al. (2007) found that rat singar1 became upregulated during polarization of cultured hippocampal neurons and remained at high levels thereafter. Reduction of singar1 expression by RNAi led to an increase in the population of neurons bearing surplus axons. Overexpression of singar1 suppressed the formation of surplus axons induced by excess amounts of shootin1 (611171), without affecting normal polarization processes.
Using mass spectrometry analysis, Hertz et al. (2019) showed that neuronally enriched mouse Rufy3 was required for caspase-mediated axon degeneration and was proteolytically cleaved after trophic deprivation. Knockout analysis demonstrated that Rufy3 functioned downstream of or in parallel to caspase-3 (600636) in axon degeneration. Structure-function analysis revealed that dephosphorylation of S34 in Rufy3 upon trophic deprivation was required for the timely degradation of Rufy3 triggered by active caspase-3. Rufy3 knockout in mouse embryos further demonstrated that Rufy3 regulated caspase-3 activation, and was essential for caspase-3-dependent developmental neuronal degeneration.
Scott (2007) mapped the RUFY3 gene to chromosome 4q13.3 based on an alignment of the RUFY3 sequence (GenBank AB020678) with the genomic sequence (build 36.2).
Hertz, N. T., Adams, E. L., Weber, R. A., Shen, R. J., O'Rourke, M. K., Simon, D. J., Zebroski, H., Olsen, O., Morgan, C. W., Mileur, T. R., Hitchcock, A. M., Sinnott Armstrong, N. A., Wainberg, M., Bassik, M. C., Molina, H., Wells, J. A., Tessier-Lavigne, M. Neuronally enriched RUFY3 is required for caspase-mediated axon degeneration. Neuron 103: 412-422, 2019. [PubMed: 31221560] [Full Text: https://doi.org/10.1016/j.neuron.2019.05.030]
Mori, T., Wada, T., Suzuki, T., Kubota, Y., Inagaki, N. Singar1, a novel RUN domain-containing protein, suppresses formation of surplus axons for neuronal polarity. J. Biol. Chem. 282: 19884-19893, 2007. [PubMed: 17439943] [Full Text: https://doi.org/10.1074/jbc.M700770200]
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]
Scott, A. F. Personal Communication. Baltimore, Md. 6/29/2007.