Structure and expression of the human cystatin C gene

Abstract

The structural organization of the gene for the human cysteine-proteinase inhibitor cystatin C was studied. Restriction-endonuclease digests of human genomic DNA hybridized with human cystatin C cDNA and genomic probes produced patterns consistent with a single cystatin C gene and, also, the presence of six closely related sequences in the human genome. A 30 kb restriction map covering the genomic region of the cystatin C gene was constructed. The positions of three polymorphic restriction sites, found at examination of digests of genomic DNA from 79 subjects, were localized in the flanking regions of the gene. The gene was cloned and the nucleotide sequence of a 7.3 kb genomic segment was determined, containing the three exons of the cystatin C structural gene as well as 1.0 kb of 5'-flanking and 2.0 kb of 3'-flanking sequences. Northern-blot experiments revealed that the cystatin C gene is expressed in every human tissue examined, including kidney, liver, pancreas, intestine, stomach, antrum, lung and placenta. The highest cystatin C expression was seen in seminal vesicles. The apparently non-tissue-specific expression of this cysteine-proteinase inhibitor gene is discussed with respect to the structure of its 5'-flanking region, which shares several features with those of housekeeping genes.

Serum cystatin C as a marker of the renal function in patients with spinal cord injury

“…5 It is produced by all nucleated cells at a constant rate, 6 freely ®ltered in the glomeruli and reabsorbed and catabolized in the proximal tubular cells. 7 The characteristics of cystatin C indicates that its serum concentration is mainly determined by GFR making cystatin C an endogenous parameter of GFR.…”

Structure, alternative splicing and chromosomal localization of the cystatin-related epididymal spermatogenic gene

“…broadly expressed [11]. Although it is well established by studies in itro that the cystatins are cysteine protease inhibitors with specificities against papain-like cysteine proteases such as cathepsins B, S, H and L, the functions of these proteins in i o are not well understood.…”

Cystatin C: current position and future prospects

“…Studies performed on sections of human tissue or cell lines have shown that when visualised by immunohistochemical labelling or messenger RNA detected by Northern blot, the protein is present in all types of cells studied (25)(26)(27). CysC is coded by a housekeeping gene, i.e., a gene expressed both constitutively and in an unregulated manner, the classical argument supporting constant production (25,28).…”