Alternative titles; symbols
HGNC Approved Gene Symbol: SIPA1
Cytogenetic location: 11q13.1 Genomic coordinates (GRCh38): 11:65,638,101-65,650,912 (from NCBI)
Hattori et al. (1995) cloned the mouse Spa1 gene based on its inducible expression in lymphoid cells stimulated with interleukin-2 (147680).
Kurachi et al. (1997) cloned the human SPA1 gene. The gene encodes a 1,042-amino acid polypeptide with a predicted mass of 130 kD. The protein contains a C-terminal leucine zipper motif and an N-terminal GTPase activating protein (GAP) domain homologous to the human RAP1GAP (600278) protein. Human and mouse Spa1 amino acid sequences are 90% identical, with their GAP domains 98% identical. Human SPA1 was expressed at high levels in lymphohematopoietic tissues and at lower levels in several other tissues. The authors noted that SPA1 and RAP1GAP appeared to have nearly segregate expression patterns. The human SPA1 protein was localized to the perinuclear region.
Hattori et al. (1995) showed that mouse Spa1 hampers mitogen-induced cell cycle progression when abnormally or prematurely expressed.
Kurachi et al. (1997) stated that SPA1 colocalized with the RAP1 (179520) and RAP2 (179540) proteins and activated these GTPases.
Wada et al. (1997) cloned the mouse genomic Sipa1 gene and found that it consists of 16 exons.
Ebrahimi et al. (1998) studied the organization of the human SIPA1 gene.
Wada et al. (1997) used fluorescence in situ hybridization (FISH) to map the human SIPA1 gene to chromosome 11q13.3. Using 2-color FISH, they determined that the human SIPA1 locus is centromeric to the CCND1 (168461) locus.
Hunter et al. (2001) identified a probable metastasis efficiency locus, called Mtes1, on proximal mouse chromosome 19 (Hunter et al., 2001) in a 10-Mb region orthologous to human 11q12-q13. To identify potential candidates for underlying Mtes1, Park et al. (2002) used multiple cross and inbred strain haplotype mapping of the Mtes1 locus in 2 mouse strains with high metastatic efficiency and 2 with low metastatic efficiency, which reduced the number of high-priority candidate genes from about 500 to 23, a more tractable number for further characterization. Park et al. (2005), using a combination of bioinformatics, sequence analysis, and in vitro and in vivo experiments, identified the signal-induced proliferation-associated gene-1 (Sipa1) as a strong candidate for underlying the Mtes1 locus. The gene was found to contain a nonsynonymous amino acid polymorphism that affected its Sipa1 Rap-GAP function. Spontaneous metastasis assays using cells ectopically expressing Sipa1 or cells with knocked-down Sipa1 expression showed that metastatic capacity was correlated with cellular Sipa1 levels. They also found that human expression data were consistent with the idea that Sipa1 concentration has a role in metastasis. Park et al. (2005) stated that, to their knowledge, this was the first demonstration of a constitutional genetic polymorphism affecting tumor metastasis.
Ishida et al. (2006) found that Spa1 -/- mice had an age-dependent increase in B220 (PTPRC; 151460)-expressing B1a lymphocytes producing anti-double-stranded DNA antibody, an altered variable kappa isotype repertoire, and lupus-like nephritis. Ishida et al. (2006) proposed that regulated RAP1 signaling in immature B cells plays a role in modifying the B-cell repertoire and in maintaining self-tolerance.
Ebrahimi, S., Wang, E., Udar, N., Arnold, E., Burbee, D., Small, K., Sawicki, M. P. Genomic organization and cloning of the human homologue of murine Sipa-1. Gene 214: 215-221, 1998. [PubMed: 9651531] [Full Text: https://doi.org/10.1016/s0378-1119(98)00212-1]
Hattori, M., Tsukamoto, N., Nur-E-Kamal, M. S. A., Rubinfeld, B., Iwai, K., Kubota, H., Maruta, H., Minato, N. Molecular cloning of a novel mitogen-inducible nuclear protein with a Ran GTPase-activating domain that affects cell cycle progression. Molec. Cell. Biol. 15: 552-560, 1995. [PubMed: 7799964] [Full Text: https://doi.org/10.1128/MCB.15.1.552]
Hunter, K. W., Broman, K. W., Le Voyer, T., Lukes, L., Cozma, D., Debies, M. T., Rouse, J., Welch, D. R. Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. Cancer Res. 61: 8866-8872, 2001. [PubMed: 11751410]
Ishida, D., Su, L., Tamura, A., Katayama, Y., Kawai, Y., Wang, S.-F., Taniwaki, M., Hamazaki, Y., Hattori, M., Minato, N. Rap1 signal controls B cell receptor repertoire and generation of self-reactive B1a cells. Immunity 24: 417-427, 2006. [PubMed: 16618600] [Full Text: https://doi.org/10.1016/j.immuni.2006.02.007]
Kurachi, H., Wada, Y., Tsukamoto, N., Maeda, M., Kubota, H., Hattori, M., Iwai, K., Minato, N. Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2: segregate expression profiles from a rap1GAP gene product. J. Biol. Chem. 272: 28081-28088, 1997. [PubMed: 9346962] [Full Text: https://doi.org/10.1074/jbc.272.44.28081]
Lifsted, T., Le Voyer, T., Williams, M., Muller, W., Klein-Szanto, A., Buetow, K. H., Hunter, K. W. Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression. Int. J. Cancer 77: 640-644, 1998. [PubMed: 9679770] [Full Text: https://doi.org/10.1002/(sici)1097-0215(19980812)77:4<640::aid-ijc26>3.0.co;2-8]
Park, Y.-G., Zhao, X., Lesueur, F., Lowy, D. R., Lancaster, M., Pharoah, P., Qian, X., Hunter, K. W. Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nature Genet. 37: 1055-1062, 2005. [PubMed: 16142231] [Full Text: https://doi.org/10.1038/ng1635]
Park, Y. G., Lukes, L., Yang, H., Debies, M. T., Samant, R. S., Welch, D. R., Lee, M., Hunter, K. W. Comparative sequence analysis in eight inbred strains of the metastasis modifier QTL candidate gene Brms1. Mammalian Genome 13: 289-292, 2002. [PubMed: 12115030] [Full Text: https://doi.org/10.1007/s00335-001-2151-6]
Wada, Y., Kubota, H., Maeda, M., Taniwaki, M., Hattori, M., Imamura, S., Iwai, K., Minato, N. Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human. Genomics 39: 66-73, 1997. [PubMed: 9027487] [Full Text: https://doi.org/10.1006/geno.1996.4464]