Intramembrane protease

Intramembrane proteases are enzymes that have the property of cleaving transmembrane domains of integral membrane proteins. All known intramembrane proteases are themselves integral membrane proteins with multiple transmembrane domains, and they have their active sites buried within the lipid bilayer of cellular membranes. Three major classes of intramembrane proteases have been discovered. The Site-2 protease (S2P) family are intramembrane metalloproteases. Presenilin, the active subunit of gamma secretase, and the signal peptide peptidase (SPP) and SPP-like group (which are distantly related to presenilin but have opposite membrane orientation) are intramembrane aspartyl proteases. The rhomboid protease family are serine proteases.

Intramembrane proteases are not evolutionarily related to classical soluble proteases, having evolved their catalytic sites by convergent evolution.

Although only recently discovered, intramembrane proteases are the focus of intense interest because of their major biological functions and their implication in many human diseases.