Alternative titles; symbols
HGNC Approved Gene Symbol: SLA
Cytogenetic location: 8q24.22 Genomic coordinates (GRCh38): 8:133,036,728-133,102,602 (from NCBI)
Pandey et al. (1995) isolated a mouse cDNA using the 2-hybrid system to screen for molecules that interact with the cytoplasmic domain of Eck, a mouse receptor protein kinase (176946). The predicted 281-amino acid protein has both SH3 and SH2 adaptor motifs similar to those in the Src family of nonreceptor tyrosine kinases but had no catalytic domain. The protein was named Slap (Src-like adaptor protein) by the authors. Recombinant Slap was shown to bind to activated Eck receptor tyrosine kinase. Angrist et al. (1995) cloned a cDNA for the putative human homolog of the gene, symbolized SLA. The predicted protein has 87% overall identity to the mouse sequence.
Meijerink et al. (1998) described the molecular cloning and characterization of the SLA protein, demonstrating that it is embedded within the genomic organization of the human thyroglobulin (TG; 188450) gene. The SLA gene was identified by exon trapping on overlapping cosmids encompassing the largest TG intron. A 2.6-kb transcript, with the highest levels of expression in fetal brain and lung, was detected on Northern blots. Two full-length cDNAs (1 alternatively spliced) were isolated from a fetal brain library, both containing an open reading frame of 276 amino acids but lacking a catalytic tyrosine kinase domain. The gene showed a high degree of cross-species similarity and appeared to be transcribed in the direction opposite to TG. They symbolized the gene SLAP (which has been used for sarcolemmal-associated protein; 602701).
Sosinowski et al. (2000) showed that SLA is a negative regulator of T-cell receptor signaling. Holland et al. (2001) demonstrated that SLA and SLA2 (606577) are both involved in downregulating T and B cell-mediated responses.
Dragone et al. (2006) found that B-cell development was altered in mice deficient in both Slap and Cbl (165360). Overexpression of Slap and Cbl in a mature mouse B-cell line caused Slap to associate via its SH2 domain with proximal components of the B-cell receptor (BCR) complex. Slap and Cbl coexpression downregulated surface and total BCR levels, suggesting that SLAP and CBL function in intersecting pathways. Dragone et al. (2006) proposed that SLAP may be necessary to develop an optimal lymphocyte repertoire.
By genomic sequence analysis, Kratchmarova et al. (2001) determined that the mouse and human SLA adaptor proteins lack kinase domains and that each gene contains 7 exons.
Using interspecific backcross analysis, Angrist et al. (1995) mapped the Slap gene to mouse chromosome 15. With a panel of somatic cell hybrid DNAs, they mapped the human SLA gene to chromosome 8q22.3-qter. Meijerink et al. (1998) pointed out that the SLA gene is located in the candidate region for the recessively inherited demyelinating neuropathy of Lom (601455). However, sequence analysis failed to identify mutations in the SLA gene in affected persons.
Angrist, M., Wells, D. E., Chakravarti, A., Pandey, A. Chromosomal localization of the mouse Src-like adapter protein (Slap) gene and its putative human homolog SLA. Genomics 30: 623-625, 1995. [PubMed: 8825655] [Full Text: https://doi.org/10.1006/geno.1995.1289]
Dragone, L. L., Myers, M. D., White, C., Gadwal, S., Sosinowski, T., Gu, H., Weiss, A. Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Proc. Nat. Acad. Sci. 103: 18202-18207, 2006. [PubMed: 17110436] [Full Text: https://doi.org/10.1073/pnas.0608965103]
Holland, S. J., Liao, X. C., Mendenhall, M. K., Zhou, X., Pardo, J., Chu, P., Spencer, C., Fu, A., Sheng, N., Yu, P., Pali, E., Nagin, A., and 14 others. Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel inhibitor of antigen receptor signaling. J. Exp. Med. 194: 1263-1276, 2001. [PubMed: 11696592] [Full Text: https://doi.org/10.1084/jem.194.9.1263]
Kratchmarova, I., Sosinowski, T., Weiss, A., Witter, K., Vincenz, C., Pandey, A. Characterization of promoter region and genomic structure of the murine and human genes encoding Src like adapter protein. Gene 262: 267-273, 2001. [PubMed: 11179692] [Full Text: https://doi.org/10.1016/s0378-1119(00)00516-3]
Meijerink, P. H. S., Yanakiev, P., Zorn, I., Grierson, A. J., Bikker, H., Dye, D., Kalaydjieva, L., Baas, F. The gene for the human Src-like adaptor protein (hSLAP) is located within the 64-kb intron of the thyroglobulin gene. Europ. J. Biochem. 254: 297-303, 1998. [PubMed: 9660183] [Full Text: https://doi.org/10.1046/j.1432-1327.1998.2540297.x]
Pandey, A., Lindberg, R. A., Dixit, V. M. Receptor orphans find a family. Curr. Biol. 5: 986-989, 1995. [PubMed: 8542290] [Full Text: https://doi.org/10.1016/s0960-9822(95)00195-3]
Sosinowski, T., Pandey, A., Dixit, V. M., Weiss, A. Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling. J. Exp. Med. 191: 463-474, 2000. [PubMed: 10662792] [Full Text: https://doi.org/10.1084/jem.191.3.463]