Megsin is named as such due to its primary expression in the mesangium, a structure associated with the capillaries in the glomerulus of the kidney. Megsin is thought to play a role in the regulation of a wide variety of processes in mesangial cells, such as matrix metabolism, cell proliferation, and apoptosis. Identification of the exact biological functions and target proteases of megsin will lead to the development of novel therapeutic approaches to glomerular diseases. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Megsin belongs to the ovalbumin family of serpins (ov-serpins), a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.
Comment:depending on the conformational state, RCL is surface accessible in the active form or buried and inserted as the central beta strand in the inactive form
Jiyao W et al.(2023). "The conserved domain database in 2023.",