InterPro domain: IPR044713

The DnaJ proteins, also known as heat shock protein 40 (Hsp40 or Hsc40), are proteins originally identified in Escherichia coli that act as cochaperones to the molecular chaperone DnaK (Hsp70), which is responsible for several cellular processes such as rescuing misfolded proteins, folding polypeptide chains, transport of polypeptides through membranes, assembly and disassembly of protein complexes, and control of regulatory proteins [ 1 ].

Structurally, the DnaJ protein consists of an N-terminal conserved domain (called 'J' domain) of about 70 amino acids, a glycine-rich region ('G' domain') of about 30 residues, a central domain containing four repeats of a CXXCXGXG motif ('CRR' domain) and a C-terminal region of 120 to 170 residues.

This entry represents a group of DnaJ domain containing proteins, including DNJA1/2/4 from humans, Scj1/Mas5/Xdj1/Apj1 from budding yeasts, and DNAJ2/3/19 from Arabidopsis. [ 2 ].

In humans, DNAJA1, DNAJA2 and HSC70 have been shown to play key roles in both the folding and degradation of wild-type and mutant CFTR (cystic fibrosis transmembrane conductance regulator) [ 3 , 4 ]. They also function as co-chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis [ 5 ].

1. Structure and function of human DnaJ homologue subfamily a member 1 (DNAJA1) and its relationship to pancreatic cancer. Biochemistry 53, 1360-72
2. Human DnaJ homologs dj2 and dj3, and bag-1 are positive cochaperones of hsc70. J Biol Chem 275, 24728-34
3. Hsp70 and DNAJA2 limit CFTR levels through degradation. PLoS One 14, e0220984
4. Selective Binding of HSC70 and its Co-Chaperones to Structural Hotspots on CFTR. Sci Rep 10, 4176
5. hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria. Cell Death Differ 11, 390-402