Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Structure and expression of the human cystatin C gene. 236 74

Tissue patterns of gene expression were analyzed by measuring mRNA levels and incorporation of radioactive amino acids for cystatin C and beta 2-microglobulin, the two extracellular proteins in the brain with the highest ratio of concentration in cerebrospinal fluid over that in blood plasma. The primary structure of rat cystatin C mRNA from choroid plexus was determined by nucleotide sequencing of cloned cDNA and the tissue patterns of gene expression were analysed by RNA blot analysis and in situ hybridization. Cystatin C was found to be composed of 120 amino acids and to contain a potential site for N-linked glycosylation. The tissue with the highest cystatin C mRNA level was the choroid plexus of the brain. Cystatin C mRNA was also detected in lower levels in other areas of the brain, testis, epididymis, seminal vesicles, prostate, ovary, submandibular gland, and, in trace amounts, in liver. Choroid plexus pieces in culture secreted radioactive cystatin C when incubated with radioactive leucine. Rat beta 2-microglobulin cDNA was cloned and identified by nucleotide sequencing and comparison of the obtained sequence with that of mouse and human beta 2-microglobulin cDNA. Tissue levels of beta 2-microglobulin mRNA in the rat were measured by hybridization to rat beta 2-microglobulin cDNA. The highest levels of beta 2-microglobulin mRNA were observed in liver and choroid plexus. Other parts of the brain and testis contained lower levels of beta 2-microglobulin mRNA.
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PMID:The cDNA structure and expression analysis of the genes for the cysteine proteinase inhibitor cystatin C and for beta 2-microglobulin in rat brain. 268 74

Two immunochemically related forms of cystatin C-like inhibitors which differ in their Mr app and isoelectric point have been found both in urine and seminal vesicles of rats. Amino-terminal sequences of these two cystatins are identical within the same fluid and exhibit a high degree of homology with that of human cystatin C. However, cystatins C purified from urine lack eight residues at their amino-terminal end when compared to those of seminal vesicles. The occurrence of two cystatin C-like components in rat fluids has been found to be due to the presence of a glycosylated form reported here as cystatin Cg which specifically binds concanavalin A and is susceptible to endo-beta-N-acetylglucosaminidase treatment.
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PMID:Two rat homologues of human cystatin C. 304 31

Two cysteine proteinase inhibitors of the cystatin C type have been purified from urine of sodium chromate-treated rats. Both strongly inhibit papain as well as rat liver cathepsin L (Ki less than 10(-11) M) whereas rat liver cathepsins B and H are inhibited to a lesser extent. They differ by their apparent molecular mass of 17 kDa and 22 kDa and by their isoelectric point greater than or equal to 9.5 and 7.7 respectively. These two molecules share complete immunochemical identity and are precipitated by antibodies directed against human cystatin C but not by anti rat thiostatin and anti rat H-kininogen antibodies. They are also found in large amounts in seminal vesicles where they represent most of the cysteine proteinase inhibitory capacity.
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PMID:Purification of the cystatin C-like inhibitors from urine of nephropathic rats. 314 92

Human cystatin C is a low molecular weight protein involved in the control of human cysteine proteinase activity as well as microbial cysteine proteinase activity threatening the integrity of tissues. The gene for cystatin C is located on the short arm of chromosome 20, spans 6.5 kb and has three exons. To understand the mechanisms for the expression of cystatin C at the transcriptional level we mapped the 5' boundary of mRNA transcripts and studied the 5'-region of the cystatin C gene in a transient expression system with chimeric constructs utilizing various fragments of 1.1 kb of the 5'-flanking region coupled to the gene for human growth hormone. Mapping of the 5'-end of human cystatin C mRNA from placenta and seminal vesicles (low to medium versus high cystatin C expression, respectively) identified three major transcription initiation sites (positions -75, -78 and -80, A of initiation ATG as +1) and three minor sites (positions -98, -101 and -103). The relative amounts of different mRNA species were approximately the same in these two tissues. Functional analysis of the 5'-region in cultured HeLa cells revealed one region (positions -279 to -156) with a strong positive effect on transcription and comprising three identical tandemly arranged GC-rich sequences.
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PMID:The human cystatin C gene promoter: functional analysis and identification of heterogeneous mRNA. 863 84

Cystatin C displays the strongest inhibitory activity of all cystatins toward lysosomal cysteine proteases in general and has a widespread distribution in human tissues and body fluids, including seminal plasma. The aim of this study was to investigate the distribution of cystatin C in the male reproductive system. Immunohistochemistry revealed a widespread distribution of cystatin C in normal tissues from the testis, epididymis, vas deferens, seminal vesicle, and prostate gland. Immunoreactive cystatin C was localized in basal and secretory epithelial cells, but also in neuroendocrine cells in the prostate, identified by immunostaining for chromogranin A. On adjacent tissue sections, we demonstrated local production of cystatin C utilizing nonradioactive in situ hybridization with a 201-base-long digoxigenin-labeled antisense RNA probe specific for the cystatin C transcript. Staining patterns obtained by immunohistochemistry and in situ hybridization correlated well. Enzyme-linked immunosorbent assay for quantitative analysis of cystatin C demonstrated that cystatin C was present at high concentrations in tissue homogenates from all locations investigated, compared to liver, muscle, spleen, and other general tissues. Western blotting of tissue homogenates revealed a predominant 15-kd cystatin C immunoreactive component in accordance with previous findings in other organs. Quantitative real-time polymerase chain reaction analysis to determine messenger RNA levels in whole tissue extracts showed that the cystatin C gene is highly expressed in the seminal vesicles and the prostate gland, indicating that the major amount of cystatin C in the male reproductive organs and seminal plasma is produced by cells in these 2 tissues. It is concluded that cystatin C is highly expressed and widely distributed throughout the male genital tract, suggesting that cystatin C is an important regulator for normal and pathological proteolysis in the male reproductive system.
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PMID:Cystatin C is highly expressed in the human male reproductive system. 1522 45