Thrombospondin-3 (THBS3)

Thrombospondin-3 (THBS3, TSP3) is a secreted glycoprotein belonging to the thrombospondin family, which consists of five members. THBS3 forms pentameric structures via a single disulfide bond and plays a role in mediating cell-to-cell and cell-to-matrix interactions. Structurally, it is highly similar to cartilage oligomeric matrix protein (COMP/Thbs5) and other pentameric thrombospondins but lacks the procollagen domain and type I repeats found in trimeric thrombospondins. THBS3 is involved in the regulation of skeletal maturation, particularly influencing postnatal bone growth and endochondral ossification in animal models. It binds calcium ions and participates in modulation of extracellular matrix structure and cell behavior, with implications for cardiac function—excess THBS3 expression is linked to sarcolemmal destabilization and exacerbation of cardiomyopathy, whereas its absence protects against heart stress injury. Disease associations involve skeletal disorders and some cancers (notably prostate cancer), but THBS3 itself is not currently a recognized therapeutic target, and no known drugs act directly on it. THBS3 is encoded by the THBS3 gene, which shares a promoter region with metaxin 1 and is primarily expressed in tissues such as heart and cartilage. The protein’s precise functional mechanisms remain incompletely characterized, with studies indicating roles in modulating integrin localization and possibly affecting the ER-stress response. Alternative mRNA splice variants exist, but the canonical protein is best described as a pentameric extracellular matrix glycoprotein.

Other names

Thrombospondin-3THBS3TSP3