P4HB mediates disulfide bond formation in Proinsulin

Stable Identifier
R-HSA-264997
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
Oxidation of cysteine to cystine in Proinsulin
ReviewStatus
5/5
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In vitro, P4HB (PDIA1) in its oxidized form (HC53,56-P4HB) mediates the correct folding of proinsulin with disulfide bond formation and is itself reduced to P4HB (Hudson et al. 2015; Winter et al. 2011). Studies of insulin processing in knockout mutant mice are consistent with this role for P4HB, while also suggesting that other disulfide isomerases, not annotated here, could play a role in this process in vivo (Jang et al. 2019).
Literature References
PubMed ID Title Journal Year
25091901 Oxidative protein folding: from thiol-disulfide exchange reactions to the redox poise of the endoplasmic reticulum

Gannon, SA, Thorpe, C, Hudson, DA

Free Radic Biol Med 2015
21308844 Protein disulfide isomerase isomerizes non-native disulfide bonds in human proinsulin independent of its peptide-binding activity

Gleiter, S, Lilie, H, Klappa, P, Winter, J

Protein Sci 2011
31184304 PDIA1/P4HB is required for efficient proinsulin maturation and ß cell health in response to diet induced obesity

Kaufman, RJ, Itkin-Ansari, P, Arvan, P, Poothong, J, Lagunas-Acosta, J, Jang, I, Pottekat, A, Yong, J, Liu, M, Scheuner, DL, Chen, Z, Charbono, A

Elife 2019
Participants
Participates
Catalyst Activity

protein-disulfide reductase activity of HC53,56-P4HB [endoplasmic reticulum lumen]

Orthologous Events
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