Oxidative protein folding in the ER

Proteins entering the endoplasmic reticulum fold in its lumen with the help of the Hsp70 chaperone BiP and form disulfide bonds through a relay in which protein disulfide isomerase oxidizes the substrate and is itself reoxidized by the flavoprotein Ero1, which passes the electrons to oxygen; animals also use peroxiredoxin-4, VKOR-family enzymes and GPX7/8. Glycoproteins are also monitored by the calnexin/calreticulin cycle. This module is the eukaryote-wide core of ER folding, written so that it can be evaluated in any genome.

Eukaryote-wide scope: PAINT places the BiP ER-lumen node and the Ero1 node at Eukaryota (taxon:2759); the PDI node carries no taxon in the source rows. Each node is shown to be an ancestor of the human protein by its IBA rows or its IBD seeds. Read as a satisfiability rule, BiP and PDI are expected in any eukaryote. Ero1 is optional because PDI has other reoxidation routes that are not modelled here (see the Ero1 part). The glycoprotein quality-control cycle (UGGT with calnexin/calreticulin) is optional: its parts are lineage-variable, and whether it is complete in every eukaryote has not been checked here. Two selectors over-match by design and say so on their families: the Hsp70 family for BiP and the PDI family for PDI. The rule therefore tests that the folding machinery's families are present, not that the ER paralog is. Molecular functions come from the human gene reviews' core functions. Not modelled: other PDI-family oxidoreductases, the alternative PDI oxidants (peroxiredoxin-4, VKOR-family enzymes, GPX7/8), the BiP co-chaperones (Sec63, ERdj proteins, Lhs1/GRP170), and the glucosidases I and II that trim N-glycans.