The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes the most abundant extracellular inhibitor of cysteine proteases, which is found in high concentrations in biological fluids and is expressed in virtually all organs of the body. A mutation in this gene has been associated with amyloid angiopathy. Expression of this protein in vascular wall smooth muscle cells is severely reduced in both atherosclerotic and aneurysmal aortic lesions, establishing its role in vascular disease. In addition, this protein has been shown to have an antimicrobial function, inhibiting the replication of herpes simplex virus. Alternative splicing results in multiple transcript variants encoding a single protein. [provided by RefSeq, Nov 2014]
Transcription factors with Perturb-seq knockdown data for CST3. 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 = CST3 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 CST3, 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 |
|---|---|---|---|---|
| chr20:23,349,714–23,351,638 | 287.4 kb | Distal (>10kb) Multiome | 1037 | |
| chr20:23,357,172–23,358,689 | 279.7 kb | Distal (>10kb) Multiome | 873 | |
| chr20:23,361,395–23,363,116 | 275.9 kb | Distal (>10kb) Multiome | 1092 | |
| chr20:23,420,902–23,421,923 | 216.4 kb | Distal (>10kb) Multiome | 823 | |
| chr20:23,628,831–23,629,352 | 8.6 kb | Proximal (<10kb) | 545 | |
| chr20:23,637,267–23,638,378 | 3 bp | At TSS Multiome | 884 | |
| chr20:23,756,639–23,757,182 | 119.0 kb | Distal (>10kb) Multiome | 118 | |
| chr20:23,870,275–23,871,018 | 232.7 kb | Distal (>10kb) Multiome | 145 |
Genomic view of the CST3 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.