Signal peptide, CUB domain and EGF-like domain containing 1 (SCUBE1)

Signal peptide, CUB domain and EGF-like domain containing 1 (SCUBE1) is a cell surface glycoprotein expressed in platelets, endothelial cells, and certain leukemic cells, where it functions as a co-receptor to potentiate signaling by several receptor tyrosine kinases, including FLT3, VEGFR, and FGFR. Structurally, SCUBE1 contains an amino-terminal signal sequence, multiple EGF-like repeats, a spacer region, three cysteine-rich motifs, and a CUB domain. In healthy tissue, it regulates vascular and platelet biology, while in pathology—particularly mixed lineage leukemia gene-rearranged (MLL-r) acute myeloid leukemia—SCUBE1 is upregulated and drives proliferative signaling. High surface expression is a poor prognosis biomarker in AML, and its selective targeting (e.g., with antibody-drug conjugates) offers a therapeutic approach in hematological cancer settings.

Other names

SCUBE1Signal peptide, CUB domain, EGF-like 1 (mouse ortholog)Signal peptide-CUB-EGF-like repeat-containing protein 1

Enhancement of receptor tyrosine kinase signaling (promotes FLT3 ligand binding and activation of FLT3-LYN axis for leukemic proliferation). ADC-mediated cell killing (antibody-drug conjugates targeting SCUBE1 induce leukemic cell death). Potential inhibition of signaling pathways when SCUBE1 is knocked down or blocked.