DnaJ heat shock protein family member C12 (DNAJC12)

DNAJC12 is a member of the Hsp40 (DnaJ) family, acting as a co-chaperone protein that interacts with Hsp70 proteins to regulate the folding, assembly, and stability of client proteins[1][2][4]. Its primary known biological role is the stabilization and maintenance of aromatic amino acid hydroxylases, enzymes critical for neurotransmitter biosynthesis (including phenylalanine hydroxylase and tyrosine hydroxylase)[1][2][4]. Mutations in DNAJC12 can cause hyperphenylalaninemia and neurological disorders, including movement disorders and intellectual disability[2][4]. DNAJC12 also modulates proteostasis in selected cancer types, supporting cell proliferation and migration—possibly by intersecting with β-catenin and estrogen receptor signaling pathways in specific tumors[2]. Structurally, DNAJC12 contains a canonical J domain necessary for client protein recognition and binding, and the C-terminal region is critical for interaction with substrates like tyrosine hydroxylase[1]. DNAJC12’s function as a chaperone is ATP-independent for substrate stabilization but can have synergistic effects with Hsc/Hsp70 ATPase activity when in complex with specific clients[1].

Other names

DnaJ homolog subfamily C member 12JDP1J domain-containing protein 1HPANBH4DnaJ (Hsp40) homolog, subfamily C, member 12J domain protein 1dnaJ homolog subfamily C member 12