Alternative titles; symbols
HGNC Approved Gene Symbol: CST1
Cytogenetic location: 20p11.21 Genomic coordinates (GRCh38): 20:23,747,562-23,750,935 (from NCBI)
The superfamily of cysteine-proteinase inhibitors comprises structurally homologous proteins which are divided into at least 3 families: family I (the stefins; see 184600), family II (the cystatins), and family III (the kininogens; see 612358). Salivary cystatins, known as cystatins S (123857), SA (123856), and SN, are mainly found in saliva, tears, and seminal plasma, whereas cystatin C (CST3; 604312) is abundant in cerebrospinal fluid, seminal plasma, milk, synovial fluid, and urine and blood plasma of patients with uremia. It is possible that these proteins play important roles in the protection of cells from inappropriate proteolysis and in the regulation of cysteine-proteinases of both host and bacterial origin (summary by Saitoh et al., 1989).
Saitoh et al. (1987) showed that the salivary-type cystatins are determined by a gene family that consists of at least 7 loci. They isolated 3 cystatin genes, CST1 for cystatin SN, CST2 for cystatin SA, and CSTP1 for a cystatin pseudogene. Saitoh et al. (1989) demonstrated that CST3, the gene that codes for cystatin C and is mutant in cerebral amyloid angiopathy of the Icelandic type (105150), has the same organization as the CST1 and CST2 genes. Southern analysis of somatic cell hybrid clones demonstrated that all members of the cystatin gene family segregate with human chromosome 20.
By immunohistochemical analysis, Dickinson et al. (2002) found that expression of type II cystatins was limited to epithelial cells. In submandibular gland from 25-week human fetus, the level of all type II cystatin mRNAs was a small fraction of adult levels, and expression increased during development. By RNase protection assay of 23 human tissues, Dickinson et al. (2002) found that the level of CST1 was highest in submandibular gland, lower in parotid gland, lacrimal gland, and gallbladder, and very low in trachea.
Rao et al. (1991) mapped the CST1 gene to a cluster of family II cystatins on the long arm of chromosome 20 at or close to 20p11.22. By fluorescence in situ hybridization, Dickinson et al. (1994) mapped the cystatin gene cluster (CST1 to 5, CST1 and 2 pseudogenes) to 20p11.2 and showed that it spans less than 905 kb.
Dickinson, D. P., Thiesse, M., Hicks, M. J. Expression of type 2 cystatin genes CST1-CST5 in adult human tissues and the developing submandibular gland. DNA Cell Biol. 21: 47-65, 2002. [PubMed: 11879580] [Full Text: https://doi.org/10.1089/10445490252810311]
Dickinson, D. P., Zhao, Y., Thiesse, M., Siciliano, M. J. Direct mapping of seven genes encoding human type 2 cystatins to a single site located at 20p11.2. Genomics 24: 172-175, 1994. [PubMed: 7896273] [Full Text: https://doi.org/10.1006/geno.1994.1595]
Rao, V. V. G., Schnittger, S., Abrahamson, M., Hansmann, I. Cystatin-C (CST3), the candidate gene for the hereditary cystatin-C amyloid angiopathy (HCCAA) maps to or close to human chromosome 20p11.22. (Abstract) Cytogenet. Cell Genet. 58: 2029 only, 1991.
Saitoh, E., Kim, H.-S., Smithies, O., Maeda, N. Human cysteine-proteinase inhibitors: nucleotide sequence analysis of three members of the cystatin gene family. Gene 61: 329-338, 1987. [PubMed: 3446578] [Full Text: https://doi.org/10.1016/0378-1119(87)90196-x]
Saitoh, E., Sabatini, L. M., Eddy, R. L., Shows, T. B., Azen, E. A., Isemura, S., Sanada, K. The human cystatin C gene (CST3) is a member of the cystatin gene family which is localized on chromosome 20. Biochem. Biophys. Res. Commun. 162: 1324-1331, 1989. [PubMed: 2764935] [Full Text: https://doi.org/10.1016/0006-291x(89)90818-8]