Reaction: PCSK2 cleaves Insulin(57-110) to yield Insulin(90-110) and C-peptide (Insulin(57-89))
- in pathway: Insulin processing
PCSK2 (Prohormone Convertase 2) cleaves C-terminal to arginine-89 between the C-peptide and the A-chain (INS 90-110) (Smeekens et al. 1992, Bailyes et al. 1995, Itoh et al. 1996, Kaufmann et al. 1997 and inferred from rat Pcsk2). The reaction occurs in immature secretory granules (Orci et al. 1985).
Overall, proinsulin in proinsulin-zinc-calcium complexes is cleaved by endopeptidases PCSK1 (Prohormone Convertase 1/3) and PCSK2 (Prohormone Convertase 2). The exopeptidase CPE (Carboxypeptidase E, also called Carboxypeptidase H) removes 2 amino acids from the carboxyl termini of the resulting B chain (INS 25-56) and C-peptide (INS 57-87). In the major pathway of processing PCSK1 cleaves between the B chain and the C-peptide, CPE removes two arginine residues from the C-terminus of the B chain, PCSK2 cleaves between the C-peptide and the A chain (INS 90-110), and CPE removes an arginine residue and a lysine residue from the C-terminus of the C-peptide. Unlike the proinsulin-zinc calcium complex, the insulin-zinc-calcium complex is not soluble and forms crystals inside the secretory granules.
Overall, proinsulin in proinsulin-zinc-calcium complexes is cleaved by endopeptidases PCSK1 (Prohormone Convertase 1/3) and PCSK2 (Prohormone Convertase 2). The exopeptidase CPE (Carboxypeptidase E, also called Carboxypeptidase H) removes 2 amino acids from the carboxyl termini of the resulting B chain (INS 25-56) and C-peptide (INS 57-87). In the major pathway of processing PCSK1 cleaves between the B chain and the C-peptide, CPE removes two arginine residues from the C-terminus of the B chain, PCSK2 cleaves between the C-peptide and the A chain (INS 90-110), and CPE removes an arginine residue and a lysine residue from the C-terminus of the C-peptide. Unlike the proinsulin-zinc calcium complex, the insulin-zinc-calcium complex is not soluble and forms crystals inside the secretory granules.
Reaction - small molecule participants:
H2O [secretory granule lumen]
Reactome.org reaction link: R-HSA-9023178
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Reaction input - small molecules:
water
Reaction output - small molecules:
Reactome.org link: R-HSA-9023178