Knock-out mouse models of proprotein convertases: unique functions or redundancy?
The members of the proprotein convertase family play a central role in the processing and/or activation of various protein precursors involved in many physiological processes and various pathologies. The proteolysis of these precursors that occur at basic residues within the general motif (K/R)-(X)-(K/R) is mediated by the proprotein convertases PC1/3, PC2, Furin, PACE4, PC4, PC5 and PC7, whereas the proteolysis of precursors within hydrophobic residues performed by the convertase S1P/SKI-1 and the convertase NARC-1/PCSK9 seems to prefer cleavages at the motif LVFAQSIP. Here we provide a comprehensive overview of their remarkable complex roles as revealed by disruption of their genes individually using generalized or conditional approaches.
Laboratory of Biochemical Neuroendocrinology, Center for Human Genetics K.U. Leuven, Belgium.
John W M
JW
Creemers
Abdel-Majid
AM
Khatib
D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D045683:Furin / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D045706:Proprotein Convertase 2 / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D045702:Proprotein Convertase 5 / Q000172:deficiency / Q000378:metabolism; D043484:Proprotein Convertases / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism; D013381:Subtilisins / Q000172:deficiency / Q000378:metabolism
C513086:Pcsk6 protein, mouse; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D013381:Subtilisins; C107583:proprotein convertase PC7; D045683:Furin; D045706:Proprotein Convertase 2