Alternative titles; symbols
HGNC Approved Gene Symbol: TAGLN
Cytogenetic location: 11q23.3 Genomic coordinates (GRCh38): 11:117,199,294-117,207,465 (from NCBI)
In contrast to fast and slow skeletal muscle cells that fuse and terminally differentiate, smooth muscle cells are able to simultaneously proliferate and express lineage-restricted proteins. One of these proteins, expressed exclusively in smooth muscles, has been referred to as SM22-alpha, a 22-kD protein with structural similarity to the vertebrate thin filament myofibrillar regulatory protein calponin (600806) and the Drosophila muscle protein mp20, neither of which play a direct role in the contractile apparatus. The protein was originally isolated by Lees-Miller et al. (1987). Nishida et al. (1991) cloned a cDNA for Sm22-alpha from a chicken gizzard smooth muscle cDNA expression library using an antibody raised against the purified protein.
Shapland et al. (1988) identified a transformation-sensitive polypeptide doublet and showed that the higher relative molecular mass polypeptide was downregulated when mesenchymal cells were (a) transformed by DNA or RNA viruses or (b) switched to non-adherent culture conditions. Shapland et al. (1993) purified the higher molecular mass isoform from sheep aorta and found that this transformation- and cell shape-sensitive isoform showed high homology to Sm22-alpha. Because the polypeptide was transformation sensitive and rapidly gelled actin, they named the molecule transgelin.
Solway et al. (1995) cloned the mouse Sm22-alpha cDNA and gene. The 1.1-kb cDNA predicted a 201-amino acid protein. Sm22-alpha mRNA was detected at high levels by Northern blot analysis in aorta, uterus, lung, intestine, and in primary cultures of rat aortic smooth muscle cells.
Thweatt et al. (1992) cloned the human SM22-alpha cDNA as part of a study to identify genes involved in replicative senescence. Northern blot analysis showed markedly higher expression in old versus young fibroblasts.
Lawson et al. (1997) further clarified the relationship between fibroblast transgelin and smooth muscle SM22-alpha. They found that the sequences are identical and that transgelin expression is not restricted to smooth muscle, since this protein is also present in normal mesenchymal cells. They also showed that transgelin, although present in secondary cultures of mouse and rat embryo fibroblasts, is absent in many apparently normal fibroblast cell lines. Transgelin downregulation may therefore be an early and sensitive marker for the onset of transformation.
Using an expression cloning strategy with HT1080 human fibrosarcoma cells, Nair et al. (2006) identified SM22 as a regulator of MMP9 (120361) expression. Stable expression of SM22 in HT1080 cells repressed MMP9 expression, whereas suppression of SM22 via small interfering RNA in human lung fibroblasts enhanced MMP9 expression and enzymatic activity. Mmp9 expression was weak in wildtype mouse uterine tissue, which constitutively expresses Sm22, but it was strong in uterine tissue from Sm22 -/- mice. Mutation analysis indicated that the N-terminal calponin homology domain of SM22, but not the actin-binding domain, mediated MMP9 repression, probably through interference with ERK1 (MAPK3; 601795) and ERK2 (MAPK1; 176948) signaling. Nair et al. (2006) concluded that SM22, which often exhibits diminished expression in cancer, regulates MMP9 expression.
Solway et al. (1995) determined that the mouse Sm22-alpha gene contains 5 coding exons. Analysis of the promoter region identified a number of cis-acting elements that are important regulators of striated muscle transcription.
By fluorescence in situ hybridization, Camoretti-Mercado et al. (1998) mapped the TAGLN gene to chromosome 11q23.2. By linkage analysis, Stanier et al. (1998) mapped the mouse Tagln gene to chromosome 9, between markers D9Mit154 and D9Mit330.
Camoretti-Mercado, B., Forsythe, S. M., LeBeau, M. M., Espinosa, R., III, Vieira, J. E., Halayko, A. J., Willadsen, S., Kurtz, B., Ober, C., Evans, G. A., Thweatt, R., Shapiro, S., Niu, Q., Qin, Y., Padrid, P. A., Solway, J. Expression and cytogenetic localization of the human SM22 gene (TAGLN). Genomics 49: 452-457, 1998. [PubMed: 9615232] [Full Text: https://doi.org/10.1006/geno.1998.5267]
Lawson, D., Harrison, M., Shapland, C. Fibroblast transgelin and smooth muscle SM22-alpha are the same protein, the expression of which is down-regulated in many cell lines. Cell Motil. Cytoskeleton 38: 250-257, 1997. [PubMed: 9384215] [Full Text: https://doi.org/10.1002/(SICI)1097-0169(1997)38:3<250::AID-CM3>3.0.CO;2-9]
Lees-Miller, J. P., Heeley, D. H., Smillie, L. B., Kay, C. M. Isolation and characterization of an abundant and novel 22-kDa protein (SM22) from chicken gizzard smooth muscle. J. Biol. Chem. 262: 2988-2993, 1987. [PubMed: 3818630]
Nair, R. R., Solway, J., Boyd, D. D. Expression cloning identifies transgelin (SM22) as a novel repressor of 92-kDa type IV collagenase (MMP-9) expression. J. Biol. Chem. 281: 26424-26436, 2006. [PubMed: 16835221] [Full Text: https://doi.org/10.1074/jbc.M602703200]
Nishida, W., Kitami, Y., Abe, M., Hiwada, K. Gene cloning and nucleotide sequence of SM22-alpha from the chicken gizzard smooth muscle. Biochem. Int. 23: 663-668, 1991. [PubMed: 1872880]
Shapland, C., Hsuan, J. J., Totty, N. F., Lawson, D. Purification and properties of transgelin: a transformation and shape change sensitive actin-gelling protein. J. Cell Biol. 121: 1065-1073, 1993. [PubMed: 8501116] [Full Text: https://doi.org/10.1083/jcb.121.5.1065]
Shapland, C., Lowings, P., Lawson, D. Identification of new actin-associated polypeptides that are modified by viral transformation and changes in cell shape. J. Cell Biol. 107: 153-161, 1988. [PubMed: 2839517] [Full Text: https://doi.org/10.1083/jcb.107.1.153]
Solway, J., Seltzer, J., Samaha, F. F., Kim, S., Alger, L. E., Niu, Q., Morrisey, E. E., Ip, H. S., Parmacek, M. S. Structure and expression of a smooth muscle cell-specific gene, SM22-alpha. J. Biol. Chem. 270: 13460-13469, 1995. [PubMed: 7768949] [Full Text: https://doi.org/10.1074/jbc.270.22.13460]
Stanier, P., Abu-Hayyeh, S., Murdoch, J. N., Eddleston, J., Copp, A. J. Paralogous Sm22-alpha (Tagln) genes map to mouse chromosomes 1 and 9: further evidence for a paralogous relationship. Genomics 51: 144-147, 1998. [PubMed: 9693045] [Full Text: https://doi.org/10.1006/geno.1998.5381]
Thweatt, R., Lumpkin, C. K., Jr., Goldstein, S. A novel gene encoding a smooth muscle protein is overexpressed in senescent human fibroblasts. Biochem. Biophys. Res. Commun. 187: 1-7, 1992. [PubMed: 1520290] [Full Text: https://doi.org/10.1016/s0006-291x(05)81449-4]