DNAJC3

DNAJC3 (p58IPK, also ERdj6/PRKRI) is an ER-resident J-domain co-chaperone with an N-terminal TPR-repeat region (nine TPR motifs) and a C-terminal J domain. It has two interlinked roles. As a co-chaperone it binds the HSP70 chaperones BiP (HSPA5) and HSC70 (HSPA8) via its J domain, stimulates their ATPase activity, and binds misfolded proteins through its TPR groove, functioning in ER protein folding and the unfolded protein response. As a stress-inducible inhibitor of the eIF2-alpha protein kinases, it binds and inhibits PKR (EIF2AK2), PERK (EIF2AK3) and GCN2 (EIF2AK4), preventing eIF2-alpha (Ser-51/52) phosphorylation and thereby restoring/attenuating protein synthesis during ER, viral, hypothermic and amino-acid-starvation stress. It is broadly expressed (high in pancreas and testis), induced via ATF6 during ER stress, and its loss causes an autosomal-recessive syndrome of juvenile-onset diabetes mellitus with multisystem neurodegeneration (ACPHD).

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.