Processing of Proinsulin to Insulin

Stable Identifier
R-MMU-216806
Type
Reaction [omitted]
Species
Mus musculus
Compartment
General
SVG |   | PPTX  | SBGN
Processing of Proinsulin to Insulin

Proinsulin in proinsulin-zinc-calcium complexes is cleaved by endopeptidases Convertase 1/3 and Convertase 2. The exopeptidase Carboxypeptidase E then removes 2 amino acids from the carboxyl termini. Unlike the proinsulin-zinc calcium complex, the insulin-zinc-calcium complex is not soluble and forms crystals inside the secretory granules. The association of carboxypeptidase E with the secretory granule membrane is inferred from studies of bovine and mouse proteins (Cool et al. 1997).

Literature References
PubMed ID Title Journal Year
9667917 The proprotein convertases

Steiner, DF

Curr Opin Chem Biol 1998
9019408 Carboxypeptidase E is a regulated secretory pathway sorting receptor: genetic obliteration leads to endocrine disorders in Cpe(fat) mice

Cool, DR, Normant, E, Shen, F, Chen, HC, Pannell, L, Zhang, Y, Loh, YP

Cell 1997
9631292 The role of assembly in insulin's biosynthesis

Dodson, G, Steiner, D

Curr Opin Struct Biol 1998
25157818 SORCS1 is necessary for normal insulin secretory granule biogenesis in metabolically stressed β cells

Kebede, MA, Oler, AT, Gregg, T, Balloon, AJ, Johnson, A, Mitok, K, Rabaglia, M, Schueler, K, Stapleton, D, Thorstenson, C, Wrighton, L, Floyd, BJ, Richards, O, Raines, S, Eliceiri, K, Seidah, NG, Rhodes, C, Keller, MP, Coon, JL, Audhya, A, Attie, AD

J. Clin. Invest. 2014
12136131 Severe block in processing of proinsulin to insulin accompanied by elevation of des-64,65 proinsulin intermediates in islets of mice lacking prohormone convertase 1/3

Zhu, X, Orci, L, Carroll, R, Norrbom, C, Ravazzola, M, Steiner, DF

Proc Natl Acad Sci U S A 2002
16158220 Zinc-ligand interactions modulate assembly and stability of the insulin hexamer -- a review

Dunn, MF

Biometals 2005
16984975 In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion

Chimienti, F, Devergnas, S, Pattou, F, Schuit, F, Garcia-Cuenca, R, Vandewalle, B, Kerr-Conte, J, Van Lommel, L, Grunwald, D, Favier, A, Seve, M

J Cell Sci 2006
Participants
Catalyst Activity
Catalyst Activity
Title
serine-type endopeptidase activity of Convertase PC2 (in immature granule) [secretory granule lumen]
Physical Entity
Activity
Title
transporter activity of Zinc Transporter8 (ZnT8) [Golgi membrane]
Physical Entity
Activity
Title
peptidase activity of Carboxypeptidase E (in immature granule) [secretory granule membrane]
Physical Entity
Activity
Title
serine-type endopeptidase activity of Pcsk1 [secretory granule lumen]
Physical Entity
Activity
This event is regulated
Orthologous Events
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