DnaJ homolog subfamily A member 1 (DNAJA1) (DNAJA1)

DnaJ homolog subfamily A member 1 (DNAJA1), commonly referred to as HDJ2, is a molecular co-chaperone of the Hsp40 family that plays a vital role in protein homeostasis by stimulating the ATPase activity of Hsp70 [UniProt P31689]. A defining biochemical characteristic of DNAJA1 is its C-terminal CXXX motif, which undergoes post-translational farnesylation by the enzyme farnesyltransferase (FTase) [PubMed: 10491278]. This modification is essential for the protein's proper intracellular localization and its function in assisting the folding of client proteins. In clinical pharmacology, the farnesylation status of HDJ2 is utilized as a sensitive pharmacodynamic biomarker to monitor the activity of farnesyltransferase inhibitors (FTIs) such as tipifarnib and lonafarnib [PubMed: 11560130]. Inhibition of FTase leads to the accumulation of unfarnesylated HDJ2 (pro-HDJ2), which serves as a surrogate measure of target engagement in patients [PubMed: 11245454]. Beyond its utility as a biomarker, DNAJA1 is implicated in the progression of several cancers, where it stabilizes oncogenic proteins like mutant p53, thereby promoting tumor cell survival and resistance to therapy [PubMed: 30655304]. Consequently, DNAJA1 is considered a potential therapeutic target in its own right for the treatment of malignancies and certain neurodegenerative disorders [PubMed: 28848015].

Other names

HDJ2HSDJHSJ2DNAJ2DJA1Heat shock protein J2HDJ2 farnesylation

Farnesyltransferase inhibitors (FTIs) block the addition of a farnesyl group to the C-terminal CXXX motif of DNAJA1 (HDJ2), which is used as a surrogate marker for FTase inhibition [PubMed: 11560130].