Endoplasmic reticulum resident protein 44 (ERp44)

Endoplasmic reticulum resident protein 44 (ERp44) is a multi-domain chaperone and oxidoreductase belonging to the protein disulfide isomerase (PDI) family, localized mainly in the endoplasmic reticulum, ER-Golgi intermediate compartment, and the cis-Golgi. ERp44 plays a key role in oxidative protein folding by forming mixed disulfide bonds with client proteins and regulating their retention or retrieval, thus ensuring quality control during protein maturation and secretion. It contains a thioredoxin-like domain with a unique CRFS active site motif and a C-terminal RDEL motif for ER localization. ERp44 is functionally important in controlling the assembly and maturation of certain secretory proteins (such as immunoglobulin M and adiponectin), and its activity is regulated by pH-dependent conformational changes involving histidine residues. Emerging evidence suggests that PDI family members, including ERp44, are implicated in cancer and neurodegenerative diseases due to their roles in proteostasis and ER stress responses, making them putative therapeutic targets.

Other names

PDIA10TXNDC4KIAA0573protein disulfide isomerase family A member 10thioredoxin domain-containing protein 4ER protein 44ERp44UNQ532/PRO1075

Redox modulation (mixed disulfide formation with client proteins, retention of immature or misfolded proteins in the ER/Golgi, regulation of ER oxidative folding); pH-dependent client binding/release (ERp44’s structure and binding to clients and receptors is regulated by pH and histidine protonation)