DnaJ heat shock protein family member B12 (DNAJB12)

DnaJ heat shock protein family member B12 (DNAJB12) is a type II Hsp40 molecular chaperone embedded in the ER membrane, exposing its J-domain to the cytosol where it recruits Hsc70/Hsp70. It is essential for the selective retention and degradation of misfolded transmembrane proteins such as CFTR, orchestrating their triage between folding and proteasome degradation (ERAD). DNAJB12 collaborates with components of the ubiquitin-proteasome system (e.g., RMA1, Derlin-1) and is involved in membrane remodeling events, including the formation of DJANGOS in the nucleus under overexpression conditions. Though not directly targeted therapeutically itself, DNAJB12 is central to the cellular management of membrane protein biogenesis and misfolding, impacting diseases like cystic fibrosis and modulating responses to certain viral infections.

Other names

DnaJ homolog subfamily B member 12DJ10FLJ20027DnaJ (Hsp40) homolog, subfamily B, member 12DNAJB12

Chaperone/co-chaperone: recruits Hsc70/Hsp70 via its J-domain, stimulates ATPase activity, and directs misfolded membrane proteins toward proteasome-mediated ER-associated degradation (ERAD). Modulates fate of CFTR and mutant variants (keeps misfolded proteins in the ER for degradation or permits escape when depleted).