Proprotein convertase 2 (PC2) also known as prohormone convertase 2 or neuroendocrine convertase 2 (NEC2) is a serine protease and proprotein convertase PC2, like proprotein convertase 1 (PC1), is an enzyme responsible for the first step in the maturation of many neuroendocrine peptides from their precursors, such as the conversion of proinsulin to insulin intermediates. To generate the bioactive form of insulin (and many other peptides), a second step involving the removal of C-terminal basic residues is required; this step is mediated by carboxypeptidases E and/or D. PC2 plays only a minor role in the first step of insulin biosynthesis, but a greater role in the first step of glucagon biosynthesis compared to PC1. PC2 binds to the neuroendocrine protein named 7B2, and if this protein is not present, proPC2 cannot become enzymatically active. 7B2 accomplishes this by preventing the aggregation of proPC2 to inactivatable forms. The C-terminal domain of 7B2 also inhibits PC2 activity until it is cleaved into smaller inactive forms that lack carboxy-terminal basic residues. Thus, 7B2 is both an activator and an inhibitor of PC2. PC2 has been identified in a number of animals, including C. elegans.[5]
In humans, proprotein convertase 2 is encoded by the PCSK2gene.[6] It is related to the bacterial enzyme subtilisin, and altogether there are 9 different subtilisin-like genes in mammals: furin, PACE4, PC4, PC5/6, PC7/8, PCSK9, and SKI1/S1P.
^"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.
^Gomez-Saladin E, Wilson DL, Dickerson IM (1994). "Isolation and in situ localization of a cDNA encoding a Kex2-like prohormone convertase in the nematode Caenorhabditis elegans". Cellular and Molecular Neurobiology. 14 (1): 9–25. doi:10.1007/bf02088586. PMID7954663. S2CID43015859.
^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.
Shen X, Li QL, Brent GA, Friedman TC (2005). "Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter". Am. J. Physiol. Endocrinol. Metab. 288 (1): E236–45. doi:10.1152/ajpendo.00144.2004. PMID15585599.
Winsky-Sommerer R, Grouselle D, Rougeot C, et al. (2003). "The proprotein convertase PC2 is involved in the maturation of prosomatostatin to somatostatin-14 but not in the somatostatin deficit in Alzheimer's disease". Neuroscience. 122 (2): 437–47. CiteSeerX10.1.1.621.1259. doi:10.1016/S0306-4522(03)00560-8. PMID14614908. S2CID16055552.
Deftos LJ, Burton D, Hastings RH, et al. (2001). "Comparative tissue distribution of the processing enzymes "prohormone thiol protease," and prohormone convertases 1 and 2, in human PTHrP-producing cell lines and mammalian neuroendocrine tissues". Endocrine. 15 (2): 217–24. doi:10.1385/ENDO:15:2:217. PMID11720250. S2CID21101668.
Ohagi S, Yoshida H, Nanjo K (1994). "[Analysis of the gene encoding human PC2, a prohormone processing enzyme]". Nippon Rinsho. 52 (10): 2544–9. PMID7983775.
Takahashi T, Ida T, Sato T, et al. (2009). "Production of n-octanoyl-modified ghrelin in cultured cells requires prohormone processing protease and ghrelin O-acyltransferase, as well as n-octanoic acid". J. Biochem. 146 (5): 675–82. doi:10.1093/jb/mvp112. PMID19628676.
