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. Thus, 7B2 is both an activator and an inhibitor of PC2.
In humans, proprotein convertase 2 is encoded by the PCSK2gene. 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.
^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)". Genomics11 (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.
Fuller JA, Brun-Zinkernagel AM, Clark AF, Wordinger RJ (2009). "Subtilisin-like proprotein convertase expression, localization, and activity in the human retina and optic nerve head.". Invest. Ophthalmol. Vis. Sci.50 (12): 5759–68. doi:10.1167/iovs.08-2616. PMID19339735.
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.". Neuroscience122 (2): 437–47. doi:10.1016/S0306-4522(03)00560-8. PMID14614908.
Wang J, Xu J, Finnerty J, et al. (2001). "The prohormone convertase enzyme 2 (PC2) is essential for processing pro-islet amyloid polypeptide at the NH2-terminal cleavage site.". Diabetes50 (3): 534–9. doi:10.2337/diabetes.50.3.534. PMID11246872.
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.". Endocrine15 (2): 217–24. doi:10.1385/ENDO:15:2:217. PMID11720250.
Ohagi S, Yoshida H, Nanjo K (1994). "[Analysis of the gene encoding human PC2, a prohormone processing enzyme]". Nippon Rinsho52 (10): 2544–9. PMID7983775.
Li QL, Jansen E, Brent GA, et al. (2000). "Interactions between the prohormone convertase 2 promoter and the thyroid hormone receptor.". Endocrinology141 (9): 3256–66. doi:10.1210/en.141.9.3256. PMID10965896.
Yoshida T, Kato K, Yokoi K, et al. (2009). "Association of gene polymorphisms with chronic kidney disease in Japanese individuals.". Int. J. Mol. Med.24 (4): 539–47. doi:10.3892/ijmm_00000263. PMID19724895.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet.36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
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.