Reactome | Processing of Proinsulin to Insulin

Processing of Proinsulin to Insulin

Stable Identifier

R-MMU-216806

Type

Reaction [omitted]

Species

Mus musculus

Compartment

secretory granule lumen, secretory granule membrane, Golgi membrane

General

SBML | | PDF

SVG | | PPTX | SBGN

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