CASP4 Inflammatory caspase. 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. Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators. 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 ultimately results in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity. Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains. Activated by direct binding to LPS without the need of an upstream sensor. Does not directly process IL1B. During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation. Belongs to the peptidase C14A family. Widely expressed, including in keratinocytes and colonic and small intestinal epithelial cells (at protein level). Not detected in brain. 5 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Apoptosis; EC; Protease
Chromosomal Location of human Ortholog: 11q22.3
Cellular Component:  AIM2 inflammasome complex; cytoplasm; cytosol; endoplasmic reticulum; endoplasmic reticulum membrane; extracellular region; IPAF inflammasome complex; mitochondrion; NLRP3 inflammasome complex; plasma membrane; protein-containing complex
Molecular Function:  CARD domain binding; cysteine-type endopeptidase activity; cysteine-type endopeptidase activity involved in apoptotic process; cysteine-type endopeptidase activity involved in apoptotic signaling pathway; cysteine-type endopeptidase activity involved in execution phase of apoptosis; protein binding
Biological Process:  activation of cysteine-type endopeptidase activity involved in apoptotic process; apoptotic process; cellular response to amyloid-beta; defense response to Gram-positive bacterium; inflammatory response; innate immune response; intrinsic apoptotic signaling pathway; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; positive regulation of inflammatory response; positive regulation of interleukin-18-mediated signaling pathway; positive regulation of tumor necrosis factor-mediated signaling pathway; protein autoprocessing; proteolysis; pyroptosis; regulation of apoptotic process; regulation of inflammatory response
Reference #:  P49662 (UniProtKB)
Alt. Names/Synonyms: apoptotic cysteine protease Mih1/TX; CASP-4; CASP4; caspase 4; caspase 4, apoptosis-related cysteine peptidase; caspase 4, apoptosis-related cysteine protease; Caspase-4; Caspase-4 subunit 1; Caspase-4 subunit 2; Caspase4; ICE and Ced-3 homolog 2; ICE(rel)-II; ICE(rel)II; ICEREL-II; ICH-2; ICH2; Mih1; Mih1/TX; Protease ICH-2; Protease TX; TX
Gene Symbols: CASP4
Molecular weight: 43,262 Da
Basal Isoelectric point: 5.69  Predict pI for various phosphorylation states
CST Pathways:  ErbB/HER Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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