DNAJC6
Description
The DNAJC6 (DnaJ heat shock protein family (Hsp40) member C6) is a protein-coding gene located on chromosome 1.
DNAJC6, also known as auxilin, is an enzyme encoded by the DNAJC6 gene in humans. It belongs to the DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJC6 proteins have three distinct domains: a J domain, a G/F-rich region, and a cysteine-rich domain. The protein tyrosine phosphatase domain and C2 domain pair of auxilin constitute a superdomain, a tandem arrangement of two nominally unrelated domains. The phosphatase domain belongs to the auxilin subfamily of lipid phosphatases and is predicted to be catalytically inactive.
DNAJC6, also known as auxilin, may act as a protein phosphatase and/or a lipid phosphatase. It functions as a co-chaperone that recruits HSPA8/HSC70 to clathrin-coated vesicles (CCVs) and promotes the ATP-dependent dissociation of clathrin from CCVs. This process is involved in clathrin-mediated endocytosis of synaptic vesicles and their recycling, as well as in intracellular trafficking. DNAJC6 binds tightly to clathrin cages, with one DNAJC6 molecule per clathrin triskelion. The HSPA8:ATP complex then binds to the clathrin-auxilin cage, initially at a ratio of one HSPA8 per triskelion. This interaction stimulates ATP hydrolysis and causes a conformational change in HSPA8. This cycle repeats three times, leading to a complex with the clathrin-auxilin cage associated with three HSPA8:ADP complexes. ATP hydrolysis of the third HSPA8:ATP complex results in the dismantling of the cage into component triskelia. DNAJC6 then dissociates from the released triskelia and is recycled to initiate another cycle of HSPA8 recruitment. DNAJC6 also participates in the early steps of CCV formation through its interaction with the GTP-bound form of DNM1.
DNAJC6 is also known as DJC6, PARK19.
