MAML2 Gene: Function, Mutations, and Role in Cancer | NCBI, UniProt, ClinVar

MAML2 encodes a member of the Mastermind-like family of transcriptional coactivators. This protein is a key component of the Notch signaling pathway, where it binds to the Notch intracellular domain (NICD) and the DNA-binding protein CSL (RBP-Jκ) to form a transcriptional activation complex. MAML2 is essential for Notch-mediated transcription and plays roles in cell differentiation, proliferation, and development. Chromosomal rearrangements involving MAML2, particularly the CRTC1-MAML2 fusion, are recurrent in mucoepidermoid carcinoma and other neoplasms.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Notch signaling pathway (KEGG hsa04330)

• Signaling by NOTCH (Reactome R-HSA-157118)

• CREB transcription factor activation (via CRTC1-MAML2 fusion)

MAML2 is a 1,156-amino acid nuclear protein that functions as a transcriptional coactivator in the Notch signaling pathway. It contains a basic domain for DNA binding and a transactivation domain. The protein interacts with the Notch intracellular domain and CSL to activate transcription of Notch target genes. In cancer, the CRTC1-MAML2 fusion protein retains the CREB-binding domain of CRTC1 and the transactivation domain of MAML2, leading to aberrant activation of CREB target genes. MAML2 is not an enzyme; it acts as a scaffold and coactivator.