This entry represents the first redox inactive TRX-like domain b found in endoplasmic reticulum resident protein 44 (ERp44). ERp44 is an endoplasmic reticulum (ER)-resident protein, induced during stress, and involved in thiol-mediated ER retention. It contains an N-terminal TRX domain with a CXFS motif followed by two redox inactive TRX-like domains, homologous to the b and b' domains of PDI. Through the formation of reversible mixed disulfides, ERp44 mediates the ER localization of Ero1alpha, a protein that oxidizes protein disulfide isomerases into their active form [, ]. ERp44 also prevents the secretion of unassembled cargo protein with unpaired cysteines. ERp44 also modulates the activity of inositol 1,4,5-triphosphate type I receptor (IP3R1), an intracellular channel protein that mediates calcium release from the ER to the cytosol []. Similar to PDI, the b domain of ERp44 is likely involved in binding to substrates.
ERp44 is an endoplasmic reticulum (ER)-resident protein that retrieves some ER-resident enzymes and immature oligomers of secretory proteins from the Golgi []. It is composed of three thioredoxin (Trx)-like domains (a, b,and b'), followed by a C-terminal extension (C tail). Domain a contains a rather unique CRFS motif. The cysteine in this motif (Cys29) is known to form mixed disulfide bonds with client proteins to promote their thiol-dependent retention. Domain a is followed by two redox inactive Trx-like domains, b and b' []. Interestingly, the interactions between ERp44 and client proteins are pH-dependent []. This entry represents domain b', the second redox inactive TRX-like domain of ERp44.
