LEM domain-containing protein 3 (LEMD3)

LEM domain-containing protein 3 (LEMD3, also known as MAN1) is an integral protein of the inner nuclear membrane, fundamental for the nuclear envelope's architecture and the regulation of key signal transduction pathways, including those mediated by transforming growth factor beta (TGF-β) and bone morphogenic proteins (BMPs). It contains a 40-amino-acid LEM domain, and a carboxy-terminal RNA recognition motif (RRM). The LEM domain enables its interaction with barrier-to-autointegration factor (BAF), contributing to chromatin tethering, while the RRM binds Smad proteins, antagonizing TGF-β and BMP signaling, thus controlling gene expression levels and cellular processes such as proliferation, differentiation, and apoptosis. LEMD3 mutations are causative in genetic diseases including osteopoikilosis, melorheostosis, and Buschke-Ollendorff syndrome. Although LEMD3 is not a therapeutic target, its loss of function or dysregulation leads to tissue remodeling defects and abnormal apoptosis

Other names

MAN1LEMD3Inner nuclear membrane protein Man1LEM domain-containing protein 3MAN antigen 1

N/A—no drugs directly target LEMD3, but it antagonizes TGF-β and BMP signaling by binding Smad2/3 (regulatory function)