Alternative titles; symbols
HGNC Approved Gene Symbol: SEPTIN2
Cytogenetic location: 2q37.3 Genomic coordinates (GRCh38): 2:241,315,355-241,354,027 (from NCBI)
Mori et al. (1996) isolated a human cDNA that encodes a protein homologous to murine H5 and Diff6 and to yeast CDC10 (603151). The NEDD5 cDNA encodes a predicted protein of 406 amino acids. The deduced peptide sequence contains conserved domains rich in basic residues, a motif of the GTPase superfamily. Different poly(A) sites account for generation of 2 transcripts. The major 3.5-kb transcript was expressed ubiquitously in all human tissues examined, and a 2.0-kb alternative transcript lacking any long AU-rich element in the 3-prime noncoding region was expressed abundantly only in testis, heart, and skeletal muscle.
Low and Macara (2006) noted that specific combinations of septins can hetero-oligomerize and form filaments in vitro and in vivo. Using fluorescence resonance energy transfer, size exclusion chromatography, and multi-angle light scattering analyses, they characterized the complex formed by SEPT2, SEPT6 (300683), and SEPT7 (603151). SEPT6 and SEPT7 interacted through a parallel coiled-coil domain, and SEPT2 interacted with SEPT6 through its C-terminal coiled-coil domain.
Kremer et al. (2007) showed that knockdown of SEPT2, SEPT6, and SEPT7 in HeLa cells caused actin stress fibers to disintegrate and cells to lose polarity. They found that these septins acted through SOCS7 (608788) to restrict nuclear accumulation of NCK (NCK1; 600508). In the absence of septin filaments, SOCS7 recruited NCK into the nucleus. Moreover, depletion of NCK from the cytoplasm triggered dissolution of actin stress fibers and loss of cell polarity. Kremer et al. (2007) also showed that the association between septins, SOCS7, and NCK played a role in the DNA damage checkpoint response. NCK entered the nucleus following DNA damage and was required for ultraviolet (UV)-induced cell cycle arrest. Furthermore, nuclear NCK was essential for activation of p53 (TP53; 191170) in response to UV-induced DNA damage. Kremer et al. (2007) concluded that septins, SOCS7, and NCK are part of a signaling pathway that couples regulation of the DNA damage response to the cytoskeleton.
Hu et al. (2010) demonstrated that ciliary membrane proteins are highly mobile, but their diffusion is impeded at the base of the cilium by a diffusion barrier. Sept2, a member of the septin family of guanosine triphosphatases that form a diffusion barrier in budding yeast, localized at the base of the ciliary membrane. Sept2 depletion resulted in loss of ciliary membrane protein localization and Sonic hedgehog (SHH; 600725) signal transduction, and inhibited ciliogenesis. Thus, Hu et al. (2010) concluded that SEPT2 is a part of a diffusion barrier at the base of the ciliary membrane and is essential for retaining receptor-signaling pathways in the primary cilium. These experiments used IMCD3 (mouse kidney inner medullary collecting duct) cells and murine embryonic fibroblasts.
Crystal Structure
Sirajuddin et al. (2007) presented the crystal structures of the human SEPT2 G domain and the heterotrimeric human SEPT2-SEPT6-SEPT7 complex. This structure revealed a universal bipolar polymer building block, composed of an extended G domain, which forms oligomers and filaments by conserved interactions between adjacent nucleotide-binding sites and/or the amino- and carboxy-terminal extensions. Unexpectedly, x-ray crystallography and electron microscopy showed that the predicted coiled coils are not involved in or required for complex and/or filament formation. The asymmetrical heterotrimers associate head-to-head to form a hexameric unit that is nonpolarized along the filament axis but is rotationally asymmetrical. Sirajuddin et al. (2007) concluded that the architecture of septin filaments differs fundamentally from that of other cytoskeletal structures.
By fluorescence in situ hybridization, Mori et al. (1996) mapped the NEDD5 gene to 2q37.
Hu, Q., Milenkovic, L., Jin, H., Scott, M. P., Nachury, M. V., Spiliotis, E. T., Nelson, W. J. A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science 329: 436-439, 2010. [PubMed: 20558667] [Full Text: https://doi.org/10.1126/science.1191054]
Kremer, B. E., Adang, L. A., Macara, I. G. Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell 130: 837-850, 2007. [PubMed: 17803907] [Full Text: https://doi.org/10.1016/j.cell.2007.06.053]
Low, C., Macara, I. G. Structural analysis of septin 2, 6, and 7 complexes. J. Biol. Chem. 281: 30697-30706, 2006. [PubMed: 16914550] [Full Text: https://doi.org/10.1074/jbc.M605179200]
Mori, T., Miura, K., Fujiwara, T., Shin, S., Inazawa, J., Nakamura, Y. Isolation and mapping of a human gene (DIFF6) homologous to yeast CDC3, CDC10, CDC11, and CDC12, and mouse Diff6. Cytogenet. Cell Genet. 73: 224-227, 1996. [PubMed: 8697812] [Full Text: https://doi.org/10.1159/000134343]
Sirajuddin, M., Farkasovsky, M., Hauer, F., Kuhlmann, D., Macara, I. G., Weyand, M., Stark, H., Wittinghofer, A. Structural insight into filament formation by mammalian septins. Nature 449: 311-315, 2007. [PubMed: 17637674] [Full Text: https://doi.org/10.1038/nature06052]