Intramembrane protease

Intramembrane proteases (IMPs), also known as intramembrane-cleaving proteases (I-CLiPs), are enzymes that have the property of cleaving transmembrane domains of integral membrane proteins.[1][2][3] 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.[4] Intramembrane proteases are responsible for proteolytic cleavage in the cell signaling process known as regulated intramembrane proteolysis (RIP).[1][5]

Intramembrane proteases are not evolutionarily related to classical soluble proteases, having evolved their catalytic sites by convergent evolution.[6][7][8]

Although only recently discovered, intramembrane proteases are of significant research interest because of their major biological functions and their relevance to human disease.[5]

  1. ^ a b Brown, MS; Ye, J; Rawson, RB; Goldstein, JL (18 February 2000). "Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans". Cell. 100 (4): 391–8. doi:10.1016/S0092-8674(00)80675-3. PMID 10693756.
  2. ^ Urban, S; Freeman, M (October 2002). "Intramembrane proteolysis controls diverse signalling pathways throughout evolution". Current Opinion in Genetics & Development. 12 (5): 512–8. doi:10.1016/s0959-437x(02)00334-9. PMID 12200155.
  3. ^ Wolfe, MS; Kopan, R (20 August 2004). "Intramembrane proteolysis: theme and variations". Science. 305 (5687): 1119–23. doi:10.1126/science.1096187. PMID 15326347.
  4. ^ Erez, E; Fass, D; Bibi, E (21 May 2009). "How intramembrane proteases bury hydrolytic reactions in the membrane". Nature. 459 (7245): 371–8. doi:10.1038/nature08146. PMID 19458713.
  5. ^ a b Cite error: The named reference kuhnle_2019 was invoked but never defined (see the help page).
  6. ^ Koonin, EV; Makarova, KS; Rogozin, IB; Davidovic, L; Letellier, MC; Pellegrini, L (2003). "The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers". Genome Biology. 4 (3): R19. doi:10.1186/gb-2003-4-3-r19. PMC 153459. PMID 12620104.
  7. ^ Lemberg, M. K.; Freeman, M. (1 November 2007). "Functional and evolutionary implications of enhanced genomic analysis of rhomboid intramembrane proteases". Genome Research. 17 (11): 1634–1646. doi:10.1101/gr.6425307. PMC 2045146. PMID 17938163.
  8. ^ Wolfe, M. S. (3 February 2009). "Intramembrane-cleaving Proteases". Journal of Biological Chemistry. 284 (21): 13969–13973. doi:10.1074/jbc.R800039200. PMC 2682844. PMID 19189971.