ERP27 (C12orf46, ERp27) research notes

UniProt Q96DN0. ER-lumenal, non-catalytic PDI-family member. 273 aa, ER-retention motif (KVEL/270-273).

Core function

• NON-CATALYTIC: lacks CXXC active-site motif -> redox-inactive PDI-family member.
• [file:human/ERP27/ERP27-uniprot.txt "Does not contain a CXXC active site motif indicating that it is a catalytically redox-inactive member of the protein disulfide isomerase family."]
• Binds unfolded proteins via a hydrophobic pocket in its C-terminal (b'-like) domain, distinguishing folded vs unfolded.
• [file "Specifically binds unfolded proteins and may recruit protein disulfide isomerase PDIA3 to unfolded substrates"]
• PMID:23192347
• Recruits/presents substrates to PDIA3/ERp57 (catalytic partner). PDIA3-binding site = residues 230-233 (E231/W232/D233 critical).
• PMID:16940051
• Homologous to non-catalytic b and b' domains of PDI; binds Delta-somatostatin (PDI test peptide).
• ER stress-induced. Pancreas-enriched (HPA tissue enriched pancreas).

Localization

• ER lumen [file "SUBCELLULAR LOCATION: Endoplasmic reticulum lumen"].

Action plan

• protein folding (GO:0006457) IBA - KEEP_AS_NON_CORE (assists folding as chaperone/substrate-presenter, not a foldase; downstream).
• NOT|protein disulfide isomerase activity (GO:0003756) IBA negated - ACCEPT (correct, lacks CXXC).
• ER lumen (GO:0005788) IEA + EXP - ACCEPT.
• protein binding (many IPI) - the FUNCTIONAL one (substrate/unfolded-protein binding, PDIA3 recruitment) is core but these GOA protein binding entries are mostly HT interactome (SGTA/EEF1D/UBQLN/HTT etc), not PDIA3. KEEP_AS_NON_CORE. Note PDIA3 interaction itself is NOT in GOA protein-binding rows (those are HT partners). Core MF captured as unfolded protein binding (GO:0051082) and protein-folding chaperone binding.
• Core MF proposals: unfolded protein binding (GO:0051082); chaperone role presenting substrates to ERp57.

GO:0051082 migration (2026-09-27)

The substrate-recognition core function now uses GO:0051787 misfolded protein binding (definition: "Binding to a misfolded protein"), replacing obsolete GO:0051082. Support: ITC shows ERp27 binds unfolded but not folded substrates and it is up-regulated in ER stress to bind accumulating misfolded proteins PMID:23192347. Carrier-specific GO:0140309 is not used because hand-off to PDIA3 is proposed rather than demonstrated, and no anti-aggregation (holdase) activity has been shown.