Reactome | P4HB mediates disulfide bond formation in Proinsulin

P4HB mediates disulfide bond formation in Proinsulin

Stable Identifier

R-HSA-264997

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum lumen

Synonyms

Oxidation of cysteine to cystine in Proinsulin

ReviewStatus

5/5

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P4HB mediates disulfide bond formation in Proinsulin

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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