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

Function

Is a positive regulator of the BMP signaling pathway, required for proper chondrogenesis, osteogenesis and skeletal development. It acts as a coreceptor for BMP ligands, particularly BMP2 and BMP4, facilitating their interactions with BMP type I receptors (PubMed:33308444). It is required for ligand-induced recruitment of BMP receptors to lipid rafts (By similarity). Binds to TGFBR2 and activates TGFB signaling. In lung cancer cells, could serve as an endogenous autocrine and paracrine ligand of TGFBR2, which could regulate TGFBR2 signaling and hence modulate epithelial-mesenchymal transition and cancer progression

Subcellular Location

Secreted; Cell surface

Disease Association

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 (SSFSC2) : An autosomal recessive disorder characterized by reduced growth, skeletal abnormalities, a distinctive craniofacial appearance, and dental anomalies. Cardiac anomalies have been reported in some patients. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Highly expressed in osteoblasts. In normal lung, mainly expressed in bronchial epithelial cells. Tends to be up-regulated in lung cancer cells

Subunit

Forms homooligomers (PubMed:33308444). Forms heterooligomers with SCUBE1 and SCUBE2 (PubMed:33308444). Interacts with TGFBR2 through the CUB domain; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with BMP2, BMP4 and BMP7; the interaction is mediated by the CUB domain (PubMed:33308444). Interacts with BMPR1A, BMPR1B and BMPR2; the interaction with BMPR1A and BMPR1B is BMP2- and BMP4-dependent (PubMed:33308444)

• Wu B.-T. et al. A novel secreted, cell-surface glycoprotein containing multiple epidermal growth factor-like repeats and one CUB domain is highly expressed in primary osteoblasts and bones. — J. Biol. Chem. (2004)
• Pfarr N. et al. Novel human gene family (CEGF) encoding mosaic proteins with EGF-like, STT2R and a CUB module: cloning and expression analysis. (NOV-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mungall A.J. et al. The DNA sequence and analysis of human chromosome 6. — Nature (2003)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Bechtel S. et al. The full-ORF clone resource of the German cDNA consortium. — BMC Genomics (2007)
• Wu Y.Y. et al. SCUBE3 is an endogenous TGF-beta receptor ligand and regulates the epithelial-mesenchymal transition in lung cancer. — Oncogene (2011)