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Identification
HMDB Protein ID HMDBP14456
Secondary Accession Numbers None
Name Caspase-4
Synonyms
  1. CASP-4
  2. ICE and Ced-3 homolog 2
  3. ICE(rel)-II
  4. Mih1
  5. Protease TX
  6. ICH-2
Gene Name CASP4
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function 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).
Pathways
  • Neutrophil extracellular trap formation
  • NOD-like receptor signaling pathway
  • Pathogenic Escherichia coli infection
  • Salmonella infection
  • Shigellosis
Reactions Not Available
GO Classification
Biological Process
regulation of inflammatory response
protein autoprocessing
apoptotic process
pyroptosis
inflammatory response
intrinsic apoptotic signaling pathway
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
innate immune response
positive regulation of tumor necrosis factor-mediated signaling pathway
execution phase of apoptosis
regulation of apoptotic process
proteolysis
cellular response to amyloid-beta
Cellular Component
endoplasmic reticulum membrane
cytosol
protein-containing complex
cytoplasm
endoplasmic reticulum
mitochondrion
plasma membrane
AIM2 inflammasome complex
IPAF inflammasome complex
NLRP3 inflammasome complex
extracellular region
Molecular Function
CARD domain binding
cysteine-type endopeptidase activity
cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 377
Molecular Weight 43261.87
Theoretical pI 5.997
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P49662
UniProtKB/Swiss-Prot Entry Name CASP4_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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