Furafylline, PDE inhibitor

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

KMT2A also known as MLL acts as a histone methyltransferase. It plays an important role in chromatin modification and transcription regulation by methylating histone H3 on lysine 4. The KMT2A gene is located on chromosome 11q23 encoding a protein with a mass around 430 kDa. Expression occurs in various tissues but is particularly high in hematopoietic cells. The mechanistic activity of KMT2A requires binding to cofactors such as menin which serves as an adapter for transcriptional regulation.

Biological function summary

Lysine methylation catalyzed by KMT2A influences gene expression and cellular differentiation. The KMT2A functions within a multi-protein complex involving menin and other cofactors including trithorax group proteins. It interacts with proteins to regulate genes important for maintaining stem cell pluripotency and hematopoiesis. The balance of KMT2A activity supports normal cell cycle progression and prevents aberrant cellular transformation.

Pathways

KMT2A occupies an essential position in the regulation of the Wnt and Notch signaling pathways. Interaction with proteins involved in these pathways such as beta-catenin in the Wnt pathway highlights its role in controlling cell fate determination and proliferation. Crosstalk with signaling molecules supports the maintenance of cellular identity particularly in embryonic development and hematopoietic lineage specification.

KMT2A abnormalities contribute to acute leukemia including acute myeloid leukemia and acute lymphoblastic leukemia. Chromosomal translocations involving KMT2A result in fusion proteins that disrupt normal gene regulation. Fusion partners like AF4 can drive oncogenic transformation. Another implication involves disorders of differentiation where dysregulation of KMT2A activity contributes to disrupted hematopoietic stem cell function and aberrant lineage specification.