This gene encodes a member of the signal peptide, complement subcomponents C1r/C1s, Uegf, bone morphogenetic protein-1 and epidermal growth factor-like domain containing protein family. Overexpression of this gene in human embryonic kidney cells results in secretion of a glycosylated form of the protein that forms oligomers and tethers to the cell surface. This gene is upregulated in lung cancer tumor tissue compared to healthy tissue and is associated with loss of the epithelial marker E-cadherin and with increased expression of vimentin, a mesenchymal marker. In addition, the protein encoded by this gene is a transforming growth factor beta receptor ligand, and when secreted by cancer cells, it can be cleaved in vitro to release the N-terminal epidermal growth factor-like repeat domain and the C-terminal complement subcomponents C1r/C1s domain. Both the full length protein and C-terminal fragment can bind to the transforming growth factor beta type II receptor to promote the epithelial-mesenchymal transition and tumor angiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Transcription factors with Perturb-seq knockdown data for SCUBE3. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = SCUBE3 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of SCUBE3, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.
| Accessibility | Element | Dist. to TSS | Link type | TFs |
|---|---|---|---|---|
| chr6:35,141,228–35,141,736 | 72.6 kb | Distal (>10kb) Multiome | 171 | |
| chr6:35,213,536–35,214,675 | 67 bp | At TSS Multiome | 310 | |
| chr6:35,258,904–35,260,476 | 45.8 kb | Distal (>10kb) Multiome | 1142 | |
| chr6:35,297,619–35,298,109 | 83.8 kb | Distal (>10kb) Multiome | 765 | |
| chr6:35,317,884–35,318,871 | 104.5 kb | Distal (>10kb) Multiome | 727 | |
| chr6:35,342,126–35,343,068 | 128.5 kb | Distal (>10kb) Multiome | 831 | |
| chr6:35,451,927–35,453,018 | 238.3 kb | Distal (>10kb) Multiome | 799 | |
| chr6:35,467,935–35,469,331 | 254.4 kb | Distal (>10kb) Multiome | 1091 | |
| chr6:35,485,138–35,486,890 | 272.5 kb | Distal (>10kb) Multiome | 400 | |
| chr6:35,490,011–35,490,813 | 276.4 kb | Distal (>10kb) Multiome | 310 | |
| chr6:35,495,972–35,498,486 | 283.2 kb | Distal (>10kb) Multiome | 939 |
Genomic view of the SCUBE3 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.