ERP29 (ERp29, ERp28, ERp31, C12orf8) research notes

UniProt P30040. ER-lumenal, non-catalytic PDI-family escort/chaperone. Homodimer. KEEL ER-retention.

Core function

• NOT a disulfide isomerase; lacks CXXC (CGHC) thioredoxin-box motif.
• PMID:9738895
• [file:human/ERP29/ERP29-uniprot.txt "Does not seem to be a disulfide isomerase. Plays an important role in the processing of secretory proteins within the endoplasmic reticulum (ER), possibly by participating in the folding of proteins in the ER."]
• Acts as a non-catalytic escort/chaperone promoting folding/processing/secretion of secretory cargo.
• Part of a large ER chaperone multiprotein complex with BiP/HSPA5, GRP94/HSP90B1, PDI, ERdj3/DNAJB11, cyclophilin B/PPIB, ERp72/PDIA4, UGGT1, SDF2L1, etc., binding nascent/unfolded Ig heavy chains.
• PMID:12475965
• Homodimer (GO:0042803 homodimerization activity).
• ER lumen localization [file "SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. Melanosome."]; also melanosome, cell surface (platelet), secreted.

Other roles (ParkinsonsUK-UCL curated, PMID:22064321 breast cancer model)

• Cancer cell growth arrest via p38 MAPK activation, p58IPK upregulation; modulates gene expression and protein secretion.
• PMID:22064321
• These (pos reg MAPK, pos/neg reg gene expr, neg reg protein secretion) are context-specific (cancer cell overexpression) downstream effects -> KEEP_AS_NON_CORE.
• protein unfolding (GO:0043335) NAS - ERp29 proposed to unfold cholera toxin/polyomavirus for membrane penetration; keep non-core.

Action plan

• NOT|protein disulfide isomerase activity (GO:0003756) IKR negated - ACCEPT (correct, lacks CXXC).
• ER / ER lumen localizations - ACCEPT.
• smooth ER (ISS/IEA), melanosome, cell surface, extracellular, membrane - KEEP_AS_NON_CORE (secondary/peripheral).
• protein folding (GO:0006457) NAS - KEEP_AS_NON_CORE (chaperone-assisted, not foldase).
• protein secretion / intracellular protein transport / ER-Golgi transport - KEEP_AS_NON_CORE (processing of secretory proteins).
• protein homodimerization activity (GO:0042803) - ACCEPT (real, homodimer).
• protein-folding chaperone binding (GO:0051087) IEA/ISS - ACCEPT (binds chaperone complex; CORE MF candidate).
• protein binding IPI (GLP1R, HT) - KEEP_AS_NON_CORE.
• cancer/MAPK/gene-expr/secretion regulation - KEEP_AS_NON_CORE.
• protein unfolding - KEEP_AS_NON_CORE.
• ER stress apoptosis regulation IEA - KEEP_AS_NON_CORE.
• Core MF: protein-folding chaperone binding (GO:0051087) + escort/chaperone in secretory protein processing.