DNAJB6 Human

DnaJ (Hsp40) Homolog, Subfamily B, Member 6, also known as DNAJB6, is a member of the DnaJ/Hsp40 family of proteins. These proteins are crucial for regulating molecular chaperone activity by stimulating the ATPase activity of Hsp70 chaperones . DNAJB6 is evolutionarily conserved and plays a significant role in protein translation, folding, unfolding, translocation, and degradation .

DNAJB6 contains a conserved 70-amino acid J domain at the N-terminus, followed by a glycine/phenylalanine-rich region . Unlike some other DnaJ proteins, DNAJB6 does not have a cysteine-rich domain . The protein exists in two isoforms: DNAJB6a and DNAJB6b. DNAJB6a, consisting of 326 residues, localizes to the nucleus, while DNAJB6b, with 242 residues, is found in both the nucleus and the cytoplasm .

The expression of DNAJB6 is ubiquitous, with the highest levels observed in the brain, particularly in the hippocampus and thalamus . In human skeletal muscle, DNAJB6 is expressed at Z discs . The protein is also expressed in various other tissues, albeit at lower levels .

DNAJB6 functions by stimulating the ATP hydrolysis activity of Hsp70 chaperones, which is essential for their activity . This stimulation is achieved through the interaction of the J domain of DNAJB6 with Hsp70 . The protein plays a critical role in preventing the aggregation of misfolded proteins, thereby protecting cells from stress-induced damage .

Mutations in the DNAJB6 gene are associated with muscular dystrophy, limb-girdle, autosomal dominant 1 . The protein’s ability to delay aggregate formation and reduce caspase-3 activation induced by mutant huntingtin highlights its potential therapeutic significance in neurodegenerative diseases .