DnaJ heat shock protein family member B3 (DNAJB3)

DnaJ heat shock protein family member B3 (DNAJB3) is a molecular co-chaperone belonging to the Hsp40 (also known as DNAJ) protein family, subfamily B. It contains a conserved J-domain at the N-terminus required for its chaperone activity in conjunction with Hsp70 proteins, playing a crucial role in protein folding and maintenance of cellular proteostasis. DNAJB3 is predominantly localized in the cytoplasm and endoplasmic reticulum, where it helps prevent protein aggregation and misfolding under conditions of cellular stress. Recent evidence highlights its role in modulating metabolic stress responses, glucose uptake (via promotion of GLUT4 transporter translocation), and insulin signaling through direct interaction with the kinase AKT1 and inhibition of stress kinases JNK1 and IKKβ. Downregulation of DNAJB3 is associated with obesity, insulin resistance, and type 2 diabetes mellitus, and restoration of DNAJB3 expression can improve insulin sensitivity, suggesting a protective function. However, DNAJB3 does not currently serve as a primary direct therapeutic target, and no drugs are known to specifically target this protein in clinical settings.

Other names

HCG3DnaJ (Hsp40) homolog subfamily B member 3dnaJ homolog subfamily B member 3MSJ-1

Chaperone interaction: assists in refolding or degradation of misfolded proteins. Direct protein-protein interaction: binds to AKT1, modulating insulin signaling and glucose uptake. Inhibits JNK1 and IKKβ kinases, mitigating metabolic/ER stress-induced insulin resistance.