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Metastasis associated 1 family, member 2 (Gene MTA2) Homo sapiensThe MTA2 (map locus Entrez/HGNC: 11q12-q13.1; Ensembl: 11q12.3) gene product, metastasis-associated protein MTA2/MTA1L1, is a 668 AA long (75.0 kDa) nuclear protein that contains a bromo-adjacent homology (BAH) domain, 144 AA (1 to 144); an EGL-27 and MTA1 homology (ELM2) domain, 112 AA (145 to 256); a SANT domain, 53 AA (263 to 315) and a GATA-type atypical zinc finger domain, 28 AA (367 to 394). MTA2 has two potential phosphoserines, Ser57 and Ser435 and one potential phosphothreonine, Thr540. MTA2 is encoded by 18 exons spanning 10 kb, Matsusue K, et al. (2001). MTA2 along with MTA1 and MTA3 and their isoforms is a member of the metastasis-associated (MTA) family of novel NR coregulators. Members of the MTA family are found in nucleosome remodeling histone deacetylase multiprotein (NuRD) complexes. These complexes function in ATP-dependent chromatin remodeling, gene silencing by DNA methylation and gene repression by histone deacetylation. Mta2 is involved in the regulation NuRD complexes wherein it modulates the activity of the core histone deacetylase (HDAC) complex, Zhang Y et al. (1999). While Mta2 is found in a growing number of cancers including epithelial ovarian cancer, Ji Y, et al. (2006) and breast cancer, Cui Y, et al. (2006), it is not correlated nearly as tightly to metastasis as is Mta1. It is thought that this may be related to the fact that Mta2 and Mta1 occur in distinctly different NuRD complexes that repress different sets of genes. MTA1 and MTA2 both exert histone deacetylase and gene repressor activity, but they are found in biochemically distinct protein complexes presumably with different functions. MTA2 appears in Mi-2/NuRD complexes composed of HDAC1/2, RbAp46/48, MBD3, Sin2 and Mi-2, a complex associated with maintaining homeostasis of the cell. MTA2 (but not MTA1) forms complexes with the transcription factors YY1 and FKBP25, Yao YL and Yang WM. (2003). YY1 is required for development. MBD3 mCpB-binding domain (MBD) is necessary and sufficient for binding to HDAC1 and MTA2, two components of the NuRD/Mi2 complex, Saito M, et al. (2002). The normal physiological roles of Mta2 are just beginning to emerge. Using Mta2 null mice, Lu X, et al. (2008) have shown that Mta2 is important for embryonic survival and that it is involved in modulating IL-4 and IFN-gamma expression in T cell immune responses. Mta2 null mice develop lupus-like autoimmune symptoms. It has also been shown that Mta2/PID expression strongly repressed p53-dependent transcriptional activity such as p53-mediated cell growth arrest and apoptosis via interaction with and deacetylation of p53, Luo J, et al. (2000). The expression of Mta2 is regulated in part by SP1 and ETS elements in its promoter, Xia L and Zhang Y. (2001) and Kaiso, a component of the human N-CoR complex, Yoon HG, et al. (2003). Sigma offers antibodies, shRNAs and other products useful for the study of the MTA2 gene products.. References: Cui Y, et al. (2006) Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose overexpression leads to estrogen-independent growth of human breast cancer cells. Mol Endocrinol. 20: 2020-2035. |
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