Signal peptide, CUB domain and EGF-like domain-containing protein 2 (SCUBE2)

Signal peptide, CUB domain and EGF-like domain-containing protein 2 (SCUBE2) is a multidomain, secreted, and membrane-associated protein comprising an N-terminal signal peptide, nine EGF-like repeats, a spacer region, three cysteine-rich motifs, and a C-terminal CUB domain[1][2][3][4][5]. SCUBE2 is broadly expressed in various tissues (heart, lung, testis, bone, vascular endothelium) and plays a key role as a mediator in Hedgehog signaling, especially in early developmental processes[2][3][6]. In cancer, SCUBE2 functions as a tumor suppressor—overexpression inhibits cell proliferation in breast, gastric, and colorectal cancer models, and low SCUBE2 expression is associated with poor prognosis[1][2][4]. At the molecular level, SCUBE2 modulates signaling pathways by antagonizing bone morphogenetic protein activity (via its CUB domain) and mediating calcium-dependent cell-cell adhesion (via EGF repeats, interacting with E-cadherin), thus inhibiting β-catenin pathway signaling[1][2]. SCUBE2 is also involved in osteoblast and chondrocyte differentiation, regulates angiogenesis through VEGFR2 interaction, and has been genetically linked to arteriovenous malformations and autism spectrum disorder[3]. Although not currently targeted by licensed drugs, its biological functions and disease associations make it a notable research target and diagnostic biomarker for oncological and developmental studies[1][2][3][4][5][6].

Other names

SCUBE2CEGP1Cegf1Cegb1FLJ16792Protein CEGP1Scube/YouCEGB1CEGF1signal peptide, CUB and EGF-like domain-containing protein 2