Reactome | Carboxypeptidase E cleaves Insulin(25-56) to yield Insulin(25-54)

Carboxypeptidase E cleaves Insulin(25-56) to yield Insulin(25-54)

Stable Identifier

R-HSA-9023163

Type

Reaction [transition]

Species

Homo sapiens

Compartment

secretory granule membrane

ReviewStatus

5/5

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Carboxypeptidase E cleaves Insulin(25-56) to yield Insulin(25-54)

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Carboxypeptidase E (CPE, also called Carboxypeptidase H) removes two arginine residues from the C-terminus of the B chain (Chen et al. 2001 and inferred from rat Cpe). 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
11462236	Missense polymorphism in the human carboxypeptidase E gene alters enzymatic activity Glaser, B, Moore, KJ, Gross, DJ, Parker, A, Qian, Y, Chan, G, Permutt, MA, Duong, Q, Chen, H, Jawahar, S, Fricker, LD, Meyer, JM, Chayen, S	Hum Mutat	2001
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