PCSK2 cleaves Insulin(57-110) to yield Insulin(90-110) and C-peptide (Insulin(57-89))

Stable Identifier
R-HSA-9023178
Type
Reaction [transition]
Species
Homo sapiens
Compartment
secretory granule lumen
ReviewStatus
5/5
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PCSK2 cleaves Insulin(57-110) to yield Insulin(90-110) and C-peptide (Insulin(57-89))
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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.
Literature References
PubMed ID Title Journal Year
7626024 Differences between the catalytic properties of recombinant human PC2 and endogenous rat PC2

Usac, EF, Arden, SD, Shennan, KI, Bailyes, EM, Docherty, K, Hutton, JC, Guest, PC

Biochem J 1995
9166668 Proinsulin conversion in GH3 cells after coexpression of human proinsulin with the endoproteases PC2 and/or PC3

Irminger, JC, Kaufmann, JE, Halban, PA, Mungall, J

Diabetes 1997
8916141 Prohormone convertases (PC1/3 and PC2) in rat and human pancreas and islet cell tumors: subcellular immunohistochemical analysis

Osamura, RY, Takekoshi, S, Itoh, J, Itoh, Y, Tanaka, S

Pathol Int 1996
1528899 Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3

Phillips, LA, Martin, S, Smeekens, SP, Carroll, R, Benig, M, Albiges-Rizo, C, Thomas, G, Montag, AG, Gardner, P, Ohagi, S

Proc Natl Acad Sci U S A 1992
3896518 Direct identification of prohormone conversion site in insulin-secreting cells

Vassalli, JD, Madsen, O, Amherdt, M, Perrelet, A, Orci, L, Ravazzola, M

Cell 1985
Participants
Input
Output
Participates
as an event of
Catalyst Activity

serine-type endopeptidase activity of PCSK2 [secretory granule lumen]

Physical Entity
PCSK2 [secretory granule lumen] (Homo sapiens)
Activity
serine-type endopeptidase activity (GO:0004252)
Inferred From
Processing of Proinsulin to Insulin (Mus musculus)
Pcsk2 (rat) cleaves human Insulin(57-110) to yield Insulin(90-110) and C-peptide (Insulin(57-89)) (Homo sapiens)
Authored
May, B  (2017-09-25)
Reviewed
Gillespie, ME  (2008-12-02)
D'Eustachio, P  (2008-12-02)
Matthews, L  (2008-12-02)
Created
May, B  (2017-09-27)
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