Disease relevance of CST4

• Production of human salivary type cysteine proteinase inhibitors (cystatins) by an Escherichia coli system and partial characterization of recombinant cystatin S and its mutant (117 arginine-->tryptophan) [1].
• We conclude that the previously observed increase of cystatin activity in whole saliva in inflammatory periodontal disease is, at least in part, due to an increased glandular output of both the isoform cystatin S (pI 4.7) and the basic cystatin C (pI 9.0) [2].
• Inhibition of the growth and cysteine proteinase activity of Porphyromonas gingivalis by human salivary cystatin S and chicken cystatin [3].
• The absolute concentrations of albumin, cystatin C, cystatin S, total IgA and total protein, but not amylase, were increased significantly in both primary and secondary Sjögren's syndrome [4].
• Based on these results we studied a possible change in the concentration of cystatin S, cystatin C, albumin, IgA, amylase activity, and cystatin activity in a whole and parotid saliva of 20 periodontitis patients as a consequence of periodontal treatment [5].

High impact information on CST4

• The novel gene, called CST4, is composed of three exons and two introns [6].
• Cystatin C had the highest molar concentration of the inhibitors in seminal plasma, cerebrospinal fluid, and milk; cystatin S in saliva and tears; and kininogen in blood plasma, synovial fluid, and amniotic fluid [7].
• Amino acid sequence data and the spot position indicate that the 4.9/13500 form might be a phosphorylated variant of cystatin S [8].
• The clone C4-4 encoded an N-terminally truncated cystatin S, whereas the others encoded cystatin SN [9].
• Two clones (C3 and C12) encoded a full-length secreted cystatin S and its leader peptide and included 5'- and 3'-untranslated regions [9].

Biological context of CST4

• Characterization of two members (CST4 and CST5) of the cystatin gene family and molecular evolution of cystatin genes [10].
• Based on the pattern of genomic instability, inter-action with checkpoint mutations and sensitivity to chromosome replication or segregation inhibitors, we conclude that overexpression of CST4 specifically interferes with mitotic chromosome segregation, and CST6 affects some aspect of DNA metabolism [11].
• Characterization and amino acid sequence of a new acidic cysteine proteinase inhibitor (cystatin SA) structurally closely related to cystatin S, from human whole saliva [12].
• The phosphorylation sites of cystatin S were determined to be Ser-Ser-Ser1(P)-Lys-Glu-Glu- for monophosphorylated cystatin S and Ser1(P)-Ser-Ser3(P)-Lys-Glu-Glu- for diphosphorylated cystatin S [13].
• This process resulted in the assignment of peptides corresponding with 118 out of the 121 amino acid residues predicted from the nucleotide sequence for cystatin SA-III [14].

Anatomical context of CST4

• Coexpression of CST1 and CST4 was also observed in the epithelial lining of the gallbladder and seminal vesicle [15].
• Immunoblotting analysis with anti-cystatin S antiserum revealed that tears and seminal plasma also contained S-type cystatins, but diphosphorylated cystatin S was detected neither in tears nor in seminal plasma and no cystatin SN was found in seminal plasma [13].
• Their relationship to rat cystatin S, a developmentally regulated rodent submandibular gland protein, remains to be established [16].
• The amount of cystatin SN accumulated in the periplasm was slightly smaller than that of cystatin S [1].
• Cystatin-like immunoreactive material was also demonstrated in human lacrimal gland using antibodies against human cystatin S [17].

Associations of CST4 with chemical compounds

• Salivary cystatin S was not an inhibitor of the cysteine proteases tested suggesting that its primary role is not as a cysteine protease inhibitor [18].
• This is the first report of the structure of cystatin SA-III deduced by amino acid sequencing techniques and indicates the sites of phosphoserine within the molecule [14].
• Cystatin SA-III was purified from human submandibular/sublingual glandular secretions by adsorption to hydroxyapatite, gel filtration chromatography, and reversed-phase HPLC [14].
• In contrast, the absolute and relative concentrations of cystatin S were diminished, particularly in patients using either valproate or phenytoin [19].
• Salivary acidic proline-rich proteins in rheumatoid arthritis [20].

Enzymatic interactions of CST4

• Full-sized cystatin SN and two phosphorylated forms of full-sized cystatin S were thus isolated [13].
• Analysis of one fraction indicated that this was a mixture of full-sized cystatin SA and non-phosphorylated cystatin S [13].

Regulatory relationships of CST4

• 3. Cystatin SA inhibited ficin and papain more strongly than cystatin S or cystatin SN did [12].

Other interactions of CST4

• The CST1 product was detected in the tracheal glands and CST4 in the kidney and prostate [15].
• Two members (CST4 and CST5) of the cystatin gene family have been characterized partially by DNA analysis [10].
• The adsorption, at hydroxyapatite surfaces of neutral cystatin SN, acidic cystatin S and the phosphoserine-containing acidic cystatin S1 was compared to that of statherin [21].
• The inhibitory activity of the both recombinant cystatins for cathepsin C was weaker than those of the native cystatin S and phosphorylated cystatin S [1].
• Recombinant cystatin S and the mutant showed virtually the same inhibitory properties for ficin, papain and cathepsin B as the native cystatin S and its monophosphorylated form [1].

Analytical, diagnostic and therapeutic context of CST4

• Human salivary cystatin S. Cloning, sequence analysis, hybridization in situ and immunocytochemistry [9].
• The purified protein was digested with endoproteinase Asp-N and the digestion products were subjected to fast atom bombardment mass spectroscopy. m/z values corresponding to 12 peptides were aligned to the sequence of cystatin S preceded by the eight-residue amino-terminal peptide detected in HSP-12 [14].
• The concentrations of cystatins in tear samples were measured by an indirect enzyme-linked immunosorbent assay (ELISA) using antibodies against human salivary cystatin S and purified cystatin S as standard [22].
• Distinct types of cystatins were identified by isoelectric focusing and immunoblotting with specific antibodies against one of the salivary acidic isoforms, cystatin S. and the widely distributed basic cystatin C [2].
• The gene expressions for the secretory protein, cystatin S (CysS), and PDE subfamilies 3A and 4D in the submaxillary gland were quantified using RT-PCR [23].

References