Alternative titles; symbols
HGNC Approved Gene Symbol: SEMA3C
Cytogenetic location: 7q21.11 Genomic coordinates (GRCh38): 7:80,742,538-80,922,389 (from NCBI)
Semaphorins, or collapsins, constitute a family characterized by the presence of a conserved semaphorin domain at the N terminus (see 601124). To identify proteins responsible for non-multidrug resistance (MDR; see 171050) to the chemotherapeutic agent cisplatin (CDDP), Yamada et al. (1997) introduced a CDDP-resistant human ovarian cancer cell cDNA expression library into CDDP-sensitive cells and selected for CDDP-resistance. They isolated a cDNA encoding a predicted protein that has 93% amino acid homology to mouse semaphorin E. The 616-amino acid human semaphorin E contains an N-terminal signal sequence of 15 amino acids that is followed by a semaphorin domain. In vitro translation of the semaphorin E cDNA yielded a 70-kD protein. The authors showed that semaphorin E is secreted by mammalian cells. By Northern blot analysis, semaphorin E was expressed as a 5.2-kb transcript in all human tissues tested.
Independently, Mangasser-Stephan et al. (1997) cloned a human semaphorin E cDNA using mRNA differential display to identify mRNAs that are upregulated in synovial fibroblasts of rheumatoid arthritis patients.
Yamada et al. (1997) found that CDDP-sensitive cells transfected with semaphorin E cDNA acquired CDDP-resistance. Semaphorin E was overexpressed in CDDP-resistant cell lines and was induced by diverse chemotherapeutic drugs and by x-ray and UV irradiation. Aberrant semaphorin E protein expression was detected immunohistochemically in 33% of recurrent squamous cell carcinomas removed from patients who had received extensive radiochemotherapy.
Lepore et al. (2006) identified multiple putative GATA-binding sites in the SEMA3C promoter region, 4 of which are conserved between mouse, rat, and human. GATA6 (601656), and not inactive GATA6 mutants, could drive expression of a reporter gene from the SEMA3C promoter.
Wiegreffe et al. (2015) showed that mouse Bcl11a (606557) directly repressed Sema3c expression by binding to regulatory elements in intron 2 of the Sema3c gene. This repression was required for development of proper neuronal cell polarity and migration of upper-layer projection neurons during mouse embryonic development.
By sequence analysis, Hillier et al. (2003) mapped the SEMA3A gene to chromosome 7q21.11.
Hillier, L. W., Fulton, R. S., Fulton, L. A., Graves, T. A., Pepin, K. H., Wagner-McPherson, C., Layman, D., Maas, J., Jaeger, S., Walker, R., Wylie, K., Sekhon, M., and 95 others. The DNA sequence of human chromosome 7. Nature 424: 157-164, 2003. [PubMed: 12853948] [Full Text: https://doi.org/10.1038/nature01782]
Lepore, J. J., Mericko, P. A., Cheng, L., Lu, M. M., Morrisey, E. E., Parmacek, M. S. GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis. J. Clin. Invest. 116: 929-939, 2006. [PubMed: 16557299] [Full Text: https://doi.org/10.1172/JCI27363]
Mangasser-Stephan, K., Dooley, S., Welter, C., Mutschler, W., Hanselmann, R. G. Identification of human semaphorin E gene expression in rheumatoid synovial cells by mRNA differential display. Biochem. Biophys. Res. Commun. 234: 153-156, 1997. [PubMed: 9168980] [Full Text: https://doi.org/10.1006/bbrc.1997.6607]
Wiegreffe, C., Simon, R., Peschkes, K., Kling, C., Strehle, M., Cheng, J., Srivatsa, S., Liu, P., Jenkins, N. A., Copeland, N. G., Tarabykin, V., Britsch, S. Bcl11a (Ctip1) controls migration of cortical projection neurons through regulation of Sema3c. Neuron 87: 311-325, 2015. [PubMed: 26182416] [Full Text: https://doi.org/10.1016/j.neuron.2015.06.023]
Yamada, T., Endo, R., Gotoh, M., Hirohashi, S. Identification of semaphorin E as a non-MDR drug resistance gene of human cancers. Proc. Nat. Acad. Sci. 94: 14713-14718, 1997. [PubMed: 9405678] [Full Text: https://doi.org/10.1073/pnas.94.26.14713]