Disease relevance of LOC443187

• We show that intact S-protein/vitronectin or its cyanogen bromide generated fragments also inhibit the hemolysis mediated by perforin from cytotoxic T-cells at 45 and 11 microM, respectively [1].
• GrB apoptosis is also activated by adenovirus, which can effectively replace perforin [2].

High impact information on LOC443187

• Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules [3].
• Finally, after experimentally verifying an optimized three-dimensional model, we have made predictions on the impact of two inherited perforin mutations of the C2 domain on calcium-dependent lipid binding and cell lysis [4].
• Calcium-dependent plasma membrane binding and cell lysis by perforin are mediated through its C2 domain: A critical role for aspartate residues 429, 435, 483, and 485 but not 491 [4].
• Granzyme M mediates a novel form of perforin-dependent cell death [5].
• Cell death is mediated by cytotoxic lymphocytes through various granule serine proteases released with perforin [5].

Biological context of LOC443187

• A 290 base pair (bp), partial sheep perforin sequence was obtained which showed 80.3% and 66.2% nucleotide identity with human and mouse perforin, respectively [6].
• The glycosaminoglycan binding site of S-protein/vitronectin is responsible for the inhibition, since a synthetic peptide corresponding to a part of this highly basic domain (amino acid residues 348-360) inhibits complement- as well as perforin-mediated cytolysis [1].

Anatomical context of LOC443187

• GammadeltaTCR+ IEL from sheep pregnant uteri were found to express perforin mRNA providing further evidence that these cells are cytotoxic [6].
• Sheep perforin: identification and expression by gammadelta T cells from pregnant sheep uterine epithelium [6].
• These data raise the likelihood that granzyme M represents a third major and specialized perforin-dependent cell death pathway that plays a significant role in death mediated by NK cells [5].
• A fluorescence microscopic assay for the activity of complement, perforin, and other cytolytic proteins which form transmembrane pores in cellular membranes is described [7].
• Resealed human erythrocyte ghosts were incubated with complement or perforin [7].

Associations of LOC443187 with chemical compounds

• The heparin binding domain of S-protein/vitronectin binds to complement components C7, C8, and C9 and perforin from cytolytic T-cells and inhibits their lytic activities [1].
• Since the cysteine-rich domain of C9 has been shown to be highly conserved in C6, C7, and C8 as well as in perforin, the inhibition of the lytic activities of these molecules by S-protein/vitronectin or by peptides corresponding to its heparin binding site may be explained by a similar mechanism [1].
• A small polar fluorescent probe (fluorescein-labeled 1-kDa dextran, FD1) which permeates through complement and perforin pores but not through normal cell membranes was added to the samples [7].
• This is in marked contrast to phosphorylcholine, the putative calcium-dependent receptor for perforin, which inhibits lysis only at greater than or equal to millimolar concentrations [8].
• Almost all the perforin molecules bind to the membrane within 1 min at 0 degrees C. The addition of EDTA abolished the binding, indicating that the effects of Ca on the membrane binding are reversible [9].

Analytical, diagnostic and therapeutic context of LOC443187

• Sheep perforin, which has not previously been described, was identified in the present study using RT-PCR based on primers from human and mouse perforin sequences [6].
• A microassay for the pore-forming activity of complement, perforin, and other cytolytic proteins based on confocal laser scanning microscopy [7].
• Methods for the purification and quantitation of GrB and perforin, and the preparation and titration of adenovirus, are described [2].

References