Heat shock protein family B member 6 (HSPB6)

Heat shock protein family B member 6 (HSPB6) is a small, cytoplasmic molecular chaperone predominately expressed in smooth, cardiac, and skeletal muscle. It plays critical roles in maintaining proteostasis and regulating cytoskeletal dynamics, especially under conditions of cellular stress. HSPB6 acts as an ATP-independent holdase, binding and stabilizing misfolded proteins, preventing their aggregation, and facilitating refolding or degradation. Upon phosphorylation (notably at serine-16 by kinases such as PKA and PKG), HSPB6 interacts with 14-3-3 proteins, leading to smooth muscle relaxation and modulation of muscle contractility. Its protective effects extend to cardiomyocyte contractility, apoptosis inhibition, and protection against amyloid toxicity. Genetic mutations in HSPB6 have been linked to myopathies and cardiomyopathies[1][2][3]. No approved drugs directly target HSPB6, but it is considered a potential therapeutic target for cardiovascular and neurodegenerative diseases, and is being investigated for its role as a biomarker and its therapeutic modulation in muscle relaxation and cytoprotection[1][2][3].

Other names

Heat shock protein beta-6HspB6HSP20PPP1R91Heat shock 20 kDa-like protein p20epididymis luminal protein 55epididymis secretory sperm binding proteinheat shock protein family B (small) member B6protein phosphatase 1 regulatory subunit 91HEL55FLJ32389

Protein kinase-mediated phosphorylation (PKA/PKG/PKD1) at serine-16 activates interaction with 14-3-3 proteins, modulating smooth muscle relaxation and cytoskeletal effects; Acetylation at C-terminal lysines (affecting muscle tone); Chaperone function preventing misfolded protein aggregation