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

Inhibition of chicken calpain II by proteins of the cystatin superfamily and alpha 2-macroglobulin was investigated. Human liver cystatins A and B, human cystatin C, chicken cystatin and rat T-kininogen were found not to be inhibitory. Inhibition was, however, observed for bovine and rat kininogens, with Ki (inhibition constant) values of 0.8 nM and 30 nM respectively. alpha 2-Macroglobulin inhibits calpain with an initial rate constant of the order of 3 X 10(4) M-1.S-1. Calpain complexed with alpha 2-macroglobulin showed only limited reactivity towards azocasein, but reacted readily with the peptide substrate Suc-Leu-Tyr-4-methyl-7-coumarylamide and with L-3-carboxy-trans-2,3-epoxypropionyl-leucylamido-(4-guanidin o)butane (E-64). The calpain in the complexes was at least partially protected from loss of activity due to autolysis. The calpain-alpha 2-macroglobulin complexes contained both the calpain subunits.
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PMID:Inhibition of chicken calpain II by proteins of the cystatin superfamily and alpha 2-macroglobulin. 244 69

Cystatins are reversible, competitive inhibitors of cysteine proteinases. Their inhibitory profiles, as well as their affinities for target enzymes, vary with different cysteine proteinases. Human cystatin C and salivary cystatin SN are 120- and 121-amino-acid (a.a.) proteins, respectively, and both contain 2 disulfide bonds. In this study, we examined the structure/function relationship of cystatin SN with respect to the inhibition of papain, with particular emphasis on the role of cystatin SN's cysteine residues, and addressed the inhibitory profiles of these two human cystatins on several cysteine proteinases (papain, clostripain, and calpain II). The full-length recombinant cystatin C and cystatin SN, and cystatin SN variants (C-truncated [C-tr; a.a. 1-102], delta 56-60 deletion, cysteine 74-->serine [C74S], cys 84-->serine [C84S], cysteine 98-->serine [C98S], and cysteine 118-->serine [C118S]) were cloned, expressed, and produced in the pET30(b) and pGEX2T Escherichia coli expression systems. All recombinant proteins were tested for the inhibition of papain, and the full-length proteins were also tested for the inhibition of clostripain and calpain II. The secondary structures of the cystatins were also determined and compared. The results showed that the full-length cystatin C and cystatin SN, and the cystatin SN variants C98S and C118S inhibited the activity of papain. However, cystatin SN C-tr and delta 56-60 variants exhibited no inhibitory activity toward papain, while the cystatin SN variants C74S and C84S exhibited slight inhibition at higher concentrations. These results suggested that in the inhibition of papain by cystatin SN, the first disulfide loop is more important than the second. In addition, cystatin C, but not cystatin SN, inhibited calpain II, while neither cystatin inhibited clostripain, and these results, in conjunction with those from other studies, indicated that cystatin C is a broader-spectrum inhibitor of cysteine proteinases than cystatin SN.
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PMID:Structure/function analysis of human cystatin SN and comparison of the cysteine proteinase inhibitory profiles of human cystatins C and SN. 1043 27

Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder often associated with rheumatoid arthritis. The etiology of LGL leukemia is not known. In order to better understand the pathogenesis of LGL leukemia, we analyzed differential gene expression using microarray technology. We found that approximately 80 genes were up-regulated and 12 genes were down-regulated when compared to normal peripheral blood mononuclear cells (PBMC). In the present study, we were interested in a group of genes involved in cytotoxic function. The up-regulated genes involved in cytotoxic function were serine proteinases (granzymes A, B, H and K) cysteine proteinases [cathepsin C, cathepsin W (lymphopain)], calpain small subunit and caspase-8. In addition, a pore-forming protein perforin, was also up-regulated. Northern blot analysis and RNase protection assays (RPA) confirmed that these genes were over-expressed in the majority of samples from LGL leukemia patients. Of interest, proteolytic inhibitors such as cystatin C, A, alpha-1 antitrypsin and metalloproteinase inhibitors were down-regulated in leukemic LGL when compared to normal peripheral blood mononuclear cells. Importantly, the pattern of gene expression in leukemic LGL resembles that seen in activated cytotoxic T cells (CTL).
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PMID:Constitutive expression of cytotoxic proteases and down-regulation of protease inhibitors in LGL leukemia. 1246 82

This study was aimed at investigating the effect of the calpain 1 (CAPN1) gene on carcass and meat quality traits in eight meat-type chicken populations, including five pure lines (developed from Chinese local breeds) and three cross-breeds. Primer pairs for the Coding Sequence (CDS) region in CAPN1 were designed from the chicken genomic sequence database. Polymorphisms were detected by polymerase chain reaction (PCR)-Single Strand Conformation Polymorphism (SSCP) and DNA sequencing. Three single nucleotide polymorphisms (SNP; C2546T, G3535A and C7198A) were detected among individuals in each population. The associations of their haplotypes (H1 = CGA, H2 = CGC, H3 = CAA, H4 = CAC, H5 = TGA and H7 = TAA) with chicken breast muscle fibre and carcass traits were analysed. Results showed that the haplotypes were associated with live weight (LW), carcass weight (CW), breast muscle weight (BMW) and leg muscle weight (LMW) (p < 0.05), and were also related to eviscerated percentage (%EP) and breast muscle fibre density (p < 0.01). H1H3 haplotype was dominant for LW, CW and BMW; H1H5 haplotype was dominant for EP; H3H4 haplotype was dominant for LMW and H1H1 haplotype was dominant for BFD. It was concluded that the CAPN1 gene may be a major gene affecting meat quality traits of chicken or it is linked with the major gene. H1H3, H1H5 and H3H4 were the most advantageous haplotypes for carcass traits whereas H1H1 was the positive haplotype for breast muscle fibre trait.
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PMID:Study on association of single nucleotide polymorphism of CAPN1 gene with muscle fibre and carcass traits in quality chicken populations. 1872 11