Proprotein convertase 1, also known asprohormone convertase,prohormone convertase 3, orneuroendocrine convertase 1 and often abbreviated asPC1/3 is anenzyme that in humans is encoded by thePCSK1gene.[5] PCSK1 andPCSK2 differentially cleaveproopiomelanocortin and they act together to processproinsulin andproglucagon inpancreatic islets.[6]
PC1/3 is an enzyme that performs theproteolytic cleavage of prohormones to their intermediate (or sometimes completely cleaved) forms.[6] It is present only inneuroendocrine cells such asbrain,pituitary andadrenal, and most often cleaves after a pair of basicresidues within prohormones but can occasionally cleave after a single arginine. It binds to a protein known as proSAAS, which also represents its endogenous inhibitor. PC1 is synthesized as a 99kDa proform quickly converted to an 87 kDa major active form, which itself is nearly completely cleaved to a 66 kDa active form within neuroendocrine cells.
Proprotein convertase 1 is the enzyme largely responsible for the first step in the biosynthesis ofinsulin. Following the action of proprotein convertase 1, a carboxypeptidase is required to remove the basic residues from the processing intermediate and generate the bioactive form of insulin. Another prohormone convertase,proprotein convertase 2 plays a more minor role in the first step of insulin biosynthesis, but a greater role in the first step ofglucagon biosynthesis. Theknockout of proprotein convertase 1 is not lethal inmice or humans, most likely due to the presence of the second convertase, although mice lacking proprotein convertase 1 activity show a number of defects including slow growth.[citation needed]
Proprotein convertase 1 is a calcium (Ca2+) activatedserine endoprotease (meaning that a serine residue is part of the active site that hydrolyzes the peptide bond within the substrate). It is related to the bacterial enzyme known assubtilisin. There are nine subtilisin homologs in mammals; in addition to proprotein convertase 1 and 2, other members of this enzyme family includefurin,PACE4,PC4,PC5/6,PC7/8,PCSK9, andSKI1/S1P.
Proprotein convertase 1 convertsprorenin into renin.[7]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Seidah NG, Mattei MG, Gaspar L, Benjannet S, Mbikay M, Chrétien M (September 1991). "Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region)".Genomics.11 (1):103–7.doi:10.1016/0888-7543(91)90106-O.PMID1765368.
