Serpin family H member 1 (HSP47) (HSP47)

Serpin family H member 1 (HSP47) is a 47 kDa heat shock protein that functions as a specialized molecular chaperone specifically for collagen synthesis within the endoplasmic reticulum (UniProt P50454). It recognizes the triple-helical structure of procollagen, specifically binding to the collagen-binding site which requires an arginine residue at the Y-position of Gly-X-Arg repeats (Widmer et al., 2012). This interaction is essential for the proper folding, stabilization, and secretion of various collagen types, including types I, II, III, IV, and V. In pathological conditions, HSP47 is significantly upregulated, driving the excessive accumulation of collagen that characterizes fibrotic diseases such as liver cirrhosis and idiopathic pulmonary fibrosis (Ito & Nagata, 2019). Therapeutic strategies targeting the HSP47 collagen-binding site include small-molecule inhibitors like Col003, which compete with procollagen for binding, and siRNA-based therapies like BMS-986263 that reduce overall protein levels (PubMed: 28334916). By inhibiting this specific chaperone, researchers aim to selectively reduce collagen deposition in fibrotic tissues without affecting other cellular protein folding processes. Clinical development has focused on localized delivery systems, such as lipid nanoparticles, to minimize systemic safety concerns related to general collagen deficiency.

Other names

SERPINH1Heat shock protein 47Collagen-binding protein 1CBP1gp46AsTP3Colligin

RNA interference (siRNA) to silence SERPINH1 gene expression; Small molecule inhibition of the HSP47-collagen binding interface