Disease relevance of CST5

• Human cystatin D. cDNA cloning, characterization of the Escherichia coli expressed inhibitor, and identification of the native protein in saliva [1].
• The data demonstrate that whereas human cystatins C and D are equipotent as inhibitors of bone resorption, cystatin D is 10-fold less potent as an inhibitor of osteoclastogenesis and 200-fold less potent as an inhibitor of cathepsin K activity [2].
• The results demonstrate that cystatin D is a potent inhibitor of coronavirus replication [3].
• When cellular toxicity was measured by 3H-thymidine uptake, cystatin D did not markedly affect cell proliferation below a 10 microM dose [3].

High impact information on CST5

• Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile [4].
• The structures reveal differences in the peptidase-interacting regions when compared with other cystatins, providing plausible explanations for the restricted inhibitory specificity of cystatin D for some papain-like peptidases and its lack of reactivity toward legumain-related enzymes [4].
• Two alleles of the cystatin D gene (CST5), encoding protein variants with either Cys or Arg as residue 26 in their 122-residue polypeptide chains, are present in the population [5].
• The inhibitory properties displayed by cystatin D suggest that it has a function in saliva as inhibitor of either endogenous or exogenous enzymes with cathepsin S- or H-like properties [5].
• A cDNA coding for cystatin D, a human member of the cystatin protein family, has been cloned after specific amplification of reverse-transcribed parotid gland RNA [1].

Chemical compound and disease context of CST5

• Cystatin D, a natural salivary cysteine protease inhibitor, inhibits coronavirus replication at its physiologic concentration [3].

Biological context of CST5

• Characterization of two members (CST4 and CST5) of the cystatin gene family and molecular evolution of cystatin genes [6].
• The gene coding for cystatin D (CST5), a cysteine proteinase inhibitor, was mapped by fluorescent in situ hybridization to human chromosome 20p11.21 [7].
• Localization of the human cystatin D gene (CST5) to chromosome 20p11.21 by in situ hybridization [7].
• When MRC-5, human diploid lung cells, were incubated with dilutions of recombinant human cystatin D from 0.65-10 microM for 1 h prior to, during and after infection with coronavirus OC43 and 229e strains, a decrease in virus yield was observed resulting in an IC50 of 0.8 microM for both virus strains [3].

Anatomical context of CST5

• Expression of type 2 cystatin genes CST1-CST5 in adult human tissues and the developing submandibular gland [8].
• On the basis of structural and functional properties, cystatin D represents a novel cysteine proteinase inhibitor possibly playing a protective role against proteinases present in the oral cavity [1].

Other interactions of CST5

• Two members (CST4 and CST5) of the cystatin gene family have been characterized partially by DNA analysis [6].
• The second cystatin pseudogene was elucidated in the clone, CST5, and it was assigned to the CSTP2 locus [6].
• Such N-terminal truncation of cystatin C caused >300-fold lower inhibition of papain, cathepsin B, L and K, whereas the cathepsin H activity was compromised by a factor of ca. 10. Similarly, truncation of cystatin D caused alleviated inhibition of all endogenous target enzymes investigated [9].

Analytical, diagnostic and therapeutic context of CST5

• Northern blot analysis revealed that the cystatin D gene is expressed in parotid gland but not in seminal vesicle, prostate, epididymis, testis, ovary, placenta, thyroid, gastric corpus, small intestine, liver, or gall-bladder tissue [10].

References