Oncology_II
Gene
CASP4
Uniprot
P49662
Protein
Caspase-4
See alternative names Mih1,
ICE(rel)-II,
ICE and Ced-3 homolog 2,
Protease TX
Uniprot Function Description
Inflammatory caspase that acts as an essential effector of NLRP3 inflammasome-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS (PubMed:23516580, PubMed:24879791, PubMed:25119034, PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352). Thiol protease that cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:7797510, PubMed:23516580). Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, followed by IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:26375003, PubMed:32109412). Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection: in later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which catalyzes cleavage of GSDMD, resulting in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion (PubMed:25121752, PubMed:26375003, PubMed:25964352, PubMed:32109412). Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752, PubMed:26375003, PubMed:25964352). Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034). Does not directly process IL1B (PubMed:7743998, PubMed:7797510, PubMed:7797592). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).
Sample type
Human EDTA plasma and serum are the recommended sample types. Human citrate plasma and heparin plasma are also accepted. For other samples types e.g cerebrospinal fluid, (CSF), tissue or cell lysates please we recommend Olink Target 96 panels. Please note that protein expression levels are expected to vary in different sample types and certain assays may be affected by interfering substances such as hemolysate.
Precision
Precision (repeatability) is calculated from linearized NPX values over LOD.
Analytical measuring range
The technical data reported below refers to the measured value in the in vitro validation assays run using known concentrations of recombinant antigen. Please note that these figures are for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples.
Dilution factor
For optimal assay readout, Olink Explore is run using different dilutions of the original samples (undiluted, 1:10, 1:100 or 1:1000). The dilution factor for this assay is noted below and should be taken into account when estimating the appropriate addressable biological concentration of the protein based on the in vitro validation data.
Sensitivity plot
The calibrator curve shown below visualizes the analytical measuring range data based on in vitro measurement of recombinant antigen. Please note that this is shown for reference only and CANNOT be used to convert NPX values to absolute concentrations for proteins measured in plasma or serum samples. The vertical dotted lines represent LLOQ and ULOQ respectively, and the horizontal line indicates the LOD.
Sample distribution plot
The plot below shows the levels of protein measured in a number of commercial plasma samples. Healthy subjects are shown in blue and samples obtained from patients with a range of diseases are shown in red. The latter include inflammatory, cardiovascular, autoimmune & neurological diseases, as well as cancer. The data is shown to give a general idea of the sort of data range to expect, but cannot cover all potential levels that may be seen in clinical samples.