Furin: the prototype mammalian subtilisin-like proprotein-processing enzyme. Endoproteolytic cleavage at paired basic residues of proproteins of the eukaryotic secretory pathway.
Furin, the translational product of the recently discovered fur gene, appears to be the first known mammalian member of the subtilisin family of serine proteases and the first known mammalian proprotein-processing enzyme with cleavage selectivity for paired basic amino acid residues. Structurally and functionally, it resembles the prohormone-processing enzyme, kexin (EC 3.4.21.61), which is encoded by the KEX2 gene of yeast Saccharomyces cerevisiae. Most likely, furin is primarily involved in the processing of precursors of proteins that are secreted via the constitutive secretory pathway. Here, we review the discovery of the fur gene and describe the isolation of cDNA clones corresponding to human and mouse fur and to two fur-like genes of Drosophila melanogaster, Dfur1 and Dfur2. We also compare the structural organization of the various deduced furin proteins to that of yeast kexin, and of other members of the subtilisin family of serine proteases. Furthermore, the biosynthesis of biologically active human and mouse furin is evaluated. Finally, the cleavage specificity for paired basic amino acid residues of human and mouse furin is demonstrated by the correct processing of the precursor for von Willebrand factor.
Van de Ven
W J
WJ
Laboratory for Molecular Oncology, University of Leuven, Belgium.
Creemers
J W
JW
Roebroek
A J
AJ
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D003001:Cloning, Molecular; D004331:Drosophila melanogaster; D045683:Furin; D006801:Humans; D007447:Invertebrate Hormones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D005810:Multigene Family; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*
D007447:Invertebrate Hormones; D011498:Protein Precursors; C076273:dfurin2; D013381:Subtilisins; D045683:Furin