Signal peptide, CUB domain and EGF-like domain-containing protein 3 (SCUBE3)

Signal peptide, CUB domain and EGF-like domain-containing protein 3 (SCUBE3) is a secreted cell-surface glycoprotein that belongs to the SCUBE family of proteins, which are characterized by an N-terminal signal peptide, multiple EGF-like repeats, and a C-terminal CUB domain (UniProt Q8IX30). It functions primarily as a co-receptor or signaling modulator, particularly within the Bone Morphogenetic Protein (BMP) and Transforming Growth Factor-beta (TGF-beta) pathways, influencing processes such as bone development and angiogenesis (NCBI Gene ID: 222663). Recent research has highlighted its role as a potent signaling molecule produced by dermal papilla cells that can trigger hair follicle stem cell activation and hair growth (Science, 2022). In oncology, SCUBE3 is often upregulated in cancers like non-small cell lung cancer and breast cancer, where it promotes epithelial-mesenchymal transition (EMT) and metastasis by enhancing TGF-beta signaling (Nature Communications, 2014). While no FDA-approved drugs currently target SCUBE3, it is being explored as a therapeutic candidate for treating androgenetic alopecia and as a potential target for anti-metastatic cancer therapies.

Other names

SCUBE3CEGP3Signal peptide, CUB domain and EGF-like protein 3

SCUBE3 acts as a co-receptor that enhances BMP and TGF-beta signaling by facilitating ligand-receptor interactions; in hair follicles, it acts as a paracrine factor produced by dermal papilla cells to stimulate hair growth (Science, 2022).