ERO1B (ERO1LB, ERO1-Lbeta) research notes

UniProt Q86YB8. ER oxidoreductin-1 beta; FAD-dependent sulfhydryl oxidase (EC 1.8.3.2), paralog of ERO1A.

Core molecular function

• Reoxidizes P4HB/PDI to drive disulfide-bond formation; passes electrons to O2 via FAD producing H2O2.
• [file:human/ERO1B/ERO1B-uniprot.txt "Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI..."]
• More active than ERO1A, looser regulation: PMID:21091435
• FAD cofactor (PMID:21091435); 7 FAD binding residues mapped by similarity to ERO1A.
• Redox-active center Cys90/Cys95 and Cys393/Cys396. Long-range regulatory disulfides; Cys130 critical for feedback.

Tissue / biology

• Enriched in professional secretory tissues, esp pancreas (islets of Langerhans), digestive tract, stomach chief cells.
• [file "In the pancreas, expressed in islets of Langerhans"]
• May function in oxidative proinsulin folding -> glucose homeostasis: [file "May be involved in oxidative proinsulin folding in pancreatic cells, hence may play a role in glucose homeostasis."]
• Induced by UPR: PMID:10818100
• Primarily ER-localized: PMID:10818100
• Homodimer (disulfide-linked); heterodimer with ERO1A.

Action plan

• Core MF: flavin-dependent sulfhydryl oxidase activity (GO:0016971) EXP - ACCEPT.
• thiol oxidase activity (GO:0016972) EXP/IDA - ACCEPT (parent).
• protein-disulfide reductase activity (GO:0015035) EXP (Reactome) x3 + IEA: ERO1 is an oxidase not reductase. The "reductase" label mislabels directionality. The physical engagement of PDI disulfides is real but the term direction is wrong -> MARK_AS_OVER_ANNOTATED.
• disulfide oxidoreductase activity (GO:0015036) IEA - ACCEPT (correct directionless parent).
• oxidoreductase activity (GO:0016491) NAS - ACCEPT general.
• FAD binding (GO:0071949) - ACCEPT.
• protein binding (PMID:20802462, PDIA3 P30101) - KEEP_AS_NON_CORE.
• ER / ER membrane / ER lumen / membrane localizations - ACCEPT (ER), KEEP_AS_NON_CORE (generic membrane).
• protein folding / protein folding in ER - KEEP_AS_NON_CORE (downstream BP).
• insulin processing (GO:0030070) TAS Reactome - KEEP_AS_NON_CORE (genuine specialized role in pancreas, proinsulin folding).