Alternative titles; symbols
HGNC Approved Gene Symbol: SEMA3B
Cytogenetic location: 3p21.31 Genomic coordinates (GRCh38): 3:50,267,652-50,277,546 (from NCBI)
The semaphorin/collapsin family of molecules plays a critical role in the guidance of growth cones during neuronal development. See semaphorin-3F (601124).
In the process of constructing a complete cosmid/P1 contig covering this region for the positional cloning of oncogenes, Sekido et al. (1996) identified 2 additional members of the human semaphorin family, semaphorin-3B, which they called semaphorin A(V), and semaphorin-3F, which they called semaphorin IV, in chromosome region 3p21.3. The 2 genes have widespread but distinct patterns of expression in nonneural tissues, and have different patterns of expression in lung cancer. Human semaphorin A(V) has 86% amino acid homology with murine semaphorin A, whereas semaphorin IV is more closely related to murine semaphorin E, with 50% homology. Sekido et al. (1996) showed that human semaphorin A(V) is translated in vitro into a 90-kD protein that accumulates in the endoplasmic reticulum. Human semaphorin A(V) was expressed in only 1 out of 23 small cell lung cancers (SCLCs) and 7 out of 16 non-SCLCs, whereas semaphorin IV was expressed in 19 out of 23 SCLCs and 13 out of 16 non-SCLCs. Mutational analysis of semaphorin A(V) revealed mutations (germline in 1 case) in 3 of 40 lung cancers.
Using Northern blot analysis, Lerman and Minna (2000) detected wide expression of a 3.4-kb SEMA3B transcript that was strongest in placenta, weaker in other tissues, including lung and testis, and not detectable in small cell lung cancer cell lines. Missense mutations were found in nonsmall cell lung cancer cell lines. The authors stated that SEMA3B is likely to be an extracellular secreted protein. Lerman and Minna (2000) concluded that SEMA3B is an attractive candidate for methylation and functional tumor suppressor gene analyses.
The short arm of chromosome 3 exhibits high loss of heterozygosity (LOH) in several types of cancer, including ovarian, kidney, lung, and testicular. In particular, overlapping homozygous deletions in lung cancers have been identified in region 3p21.3; more than 90% of small cell lung cancers (182280) exhibit LOH at this site. To examine the question of whether the SEMA3B gene, which resides on 3p21.3, may be a tumor suppressor gene, Tse et al. (2002) analyzed the effects of SEMA3B on HEY cells, an ovarian cancer cell line. They found that HEY cells expressing SEMA3B diminished tumorigenicity in nude mice. SEMA3B also markedly reduced the anchorage independence of HEY cells.
Gong et al. (2003) described a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes, and pathways. They demonstrated that Sema3b is involved in axon-target interactions. Sema3b can act to repulse axons expressing neuropilin-2 (NPN2; 602070) and can antagonize the repulsive action of Sema3a (603961) on axonal growth cones expressing neuropilin-1 (602069). Visualization of the expression of the enhanced green fluorescent protein (EGFP) reporter in Sema3b BAC transgenic mice predicted an important role for Sema3b in the formation of the circuitry of the olfactory system. In embryonic day 15.5 embryos, Sema3b expression in the developing olfactory system was widespread. Intense expression was also present in the developing vomeronasal organ.
By genomic sequence analysis, Lerman and Minna (2000) determined that the SEMA3B gene contains 17 exons and spans 8 to 10 kb.
Sekido et al. (1996) mapped the SEMA3B and SEMA3F genes to chromosome 3p21.3. The 2 genes lie within approximately 70 kb of each other. SEMA3B and SEMA3F are flanked by 2 GTP-binding protein genes, GNAI2 (139360) and GNAT1 (139330). Sekido et al. (1996) stated that other human semaphorin gene sequences, for example, human semaphorin III (SEMA3A; 603961) and homologs of murine semaphorins B (SEMA4A) and C (SEMA4B; 617029), are not located on chromosome 3.
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., Heintz, N. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425: 917-925, 2003. [PubMed: 14586460] [Full Text: https://doi.org/10.1038/nature02033]
Lerman, M. I., Minna, J. D. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. Cancer Res. 60: 6116-6133, 2000. [PubMed: 11085536]
Sekido, Y., Bader, S., Latif, F., Chen, J.-Y., Duh, F.-M., Wei, M.-H., Albanesi, J. P., Lee, C.-C., Lerman, M. I., Minna, J. D. Human semaphorins A(V) and IV reside in the 3p21.3 small cell lung cancer deletion region and demonstrate distinct expression patterns. Proc. Nat. Acad. Sci. 93: 4120-4125, 1996. [PubMed: 8633026] [Full Text: https://doi.org/10.1073/pnas.93.9.4120]
Tse, C., Xiang, R. H., Bracht, T., Naylor, S. L. Human semaphorin 3B (SEMA3B) located at chromosome 3p21.3 suppresses tumor formation in an adenocarcinoma cell line. Cancer Res. 62: 542-546, 2002. [PubMed: 11809707]