Alternative titles; symbols
HGNC Approved Gene Symbol: MTA3
Cytogenetic location: 2p21 Genomic coordinates (GRCh38) : 2:42,494,110-42,756,946 (from NCBI)
By sequencing clones obtained from an adult brain cDNA library, Nagase et al. (1999) cloned MTA3, which they designated KIAA1266. The deduced 601-amino acid protein contains a BAH domain, an ELM2 domain, a MYB (189990)-like DNA-binding domain, and a GATA zinc finger, suggesting it is involved in nucleic acid management. MTA3 shares 69% amino acid identity with MTA1 (603526). RT-PCR ELISA detected intermediate MTA3 expression in adult and fetal brain and in all specific brain regions examined. Intermediate expression was also detected in ovary, and lower levels were detected in kidney and lung. Little to no expression was found in all other tissues examined.
By searching genomic and EST databases for sequences similar to MTA1, followed by RT-PCR of HeLa and MCF7 breast cancer cells, Fujita et al. (2003) cloned 2 MTA3 splice variants. The transcripts differ in their 3-prime terminal exons and encode 515- and 594-amino acid proteins with unique C termini. The authors referred to the proteins as MTA3 and MTA3L, respectively.
By coimmunoprecipitation of endogenous or epitope-tagged proteins from several human cell lines, Fujita et al. (2003) determined that MTA3 is a component of the NURD (nucleosome remodeling and histone deacetylation) complex. Expression of MTA3 was tightly linked with estrogen action, and transcriptional repression by MTA3 was histone deacetylase-dependent. SNAI1 (604238), a master regulator of epithelial-to-mesenchymal transition (EMT), was also a direct MTA3 target. Experimental manipulation of MTA3 effected SNAI1 and E-cadherin (192090) levels, events associated with changes in epithelial architecture and invasive cell growth.
Mishra et al. (2004) found that both estrogen receptor (ER; 133430) and MTA1 were recruited to the estrogen response element (ERE) half site of the MTA3 promoter region. Estrogen stimulated MTA3 promoter activity in a corepressor-sensitive manner. Modulation of ER functions by corepressors or coactivators resulted in the suppression or stimulation of ER recruitment to the MTA3 promoter, consequently affecting the expression of EMT components. Mishra et al. (2004) concluded that dynamic changes in the levels of ER coregulators influence ER regulation of MTA3 and MTA3-mediated EMT.
Mishra et al. (2004) determined that the promoter region of the MTA3 gene contains 3 ERE half sites (TGACC) located in the vicinity of AP1 (165160)-binding sites.
By radiation hybrid analysis, Nagase et al. (1999) mapped the MTA3 gene to chromosome 2.
Fujita, N., Jaye, D. L., Kajita, M., Geigerman, C., Moreno, C. S., Wade, P. A. MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113: 207-219, 2003. [PubMed: 12705869] [Full Text: https://doi.org/10.1016/s0092-8674(03)00234-4]
Mishra, S. K., Talukder, A. H., Gururaj, A. E., Yang, Z., Singh, R. R., Mahoney, M. G., Franci, C., Vadlamudi, R. K., Kumar, R. Upstream determinants of estrogen receptor-alpha regulation of metastatic tumor antigen 3 pathway. J. Biol. Chem. 279: 32709-32715, 2004. [PubMed: 15169784] [Full Text: https://doi.org/10.1074/jbc.M402942200]
Nagase, T., Ishikawa, K., Kikuno, R., Hirosawa, M., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6: 337-345, 1999. [PubMed: 10574462] [Full Text: https://doi.org/10.1093/dnares/6.5.337]