Carboxypeptidase E cleaves C-peptide (Insulin(57-89)) to yield C-peptide (Insulin(57-87))

Stable Identifier
R-HSA-9023159
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

Carboxypeptidase E (CPE, also called Carboxypeptidase H) cleaves the C-terminal arginine-89 and lysine-88 from the C-peptide (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
3896518 Direct identification of prohormone conversion site in insulin-secreting cells

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

Cell 1985
11462236 Missense polymorphism in the human carboxypeptidase E gene alters enzymatic activity

Chen, H, Jawahar, S, Qian, Y, Duong, Q, Chan, G, Parker, A, Meyer, JM, Moore, KJ, Chayen, S, Gross, DJ, Glaser, B, Permutt, MA, Fricker, LD

Hum Mutat 2001
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
metallocarboxypeptidase activity of CPE:Zn2+ [secretory granule membrane]
Physical Entity
Activity
Inferred From
Authored
Reviewed