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MAML2 (mastermind-like protein 2), also known as MAM2, MAM3 or MLLMAML2, is a nuclear speckle protein that acts as a transcriptional co-activator for Notch receptors. The Notch signaling pathway influences cell fate by regulating the ability of precursor cells to properly respond to developmental signals. MAML2 is a member of the mastermind-like family of proteins that are human homologs of the Drosophila melanogaster mastermind protein. Through its N-terminal region, MAML2 interacts with the ankyrin repeats of the Notch proteins Notch 1, Notch 2, Notch 3 and Notch 4. This interaction leads to formation of a DNA-binding complex with the Notch proteins and RBP-J a complex that can then induce HES1 gene expression. While the N-terminal domain of MAML2 is essential for proper Notch binding, the C-terminal domain of MAML2 is essential for transcriptional activation. A chromosomal aberration involving the gene encoding MAML2 is implicated in mucoepidermoid carcinomas, clear cell hidradenomas and benign Warthin tumors.
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