CASP1

This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce 2 subunits, large and small, that dimerize to form the active enzyme. This gene was identified by its ability to proteolytically cleave and activate the inactive precursor of interleukin-1, a cytokine involved in the processes such as inflammation, septic shock, and wound healing. This gene has been shown to induce cell apoptosis and may function in various developmental stages. Studies of a similar gene in mouse suggest a role in the pathogenesis of Huntington disease. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

Caspase 1

Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides (PubMed:15326478, PubMed:1574116, PubMed:7876192, PubMed:15498465, PubMed:26375003, PubMed:32051255).
Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes (PubMed:1574116, PubMed:7876192, PubMed:15498465, PubMed:15326478, PubMed:32051255).
Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:1574116, PubMed:7876192, PubMed:15498465).
Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:26375003).
In contrast to cleavage of interleukins IL1B and IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32051255, PubMed:32109412, PubMed:32553275).
Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590).
In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly (PubMed:20197547).
Isoform Delta: Apoptosis inactive.
Isoform Epsilon: Apoptosis inactive.

Apoptotic process Source: ProtInc
Cellular response to cytokine stimulus Source: Reactome
Cellular response to interferon-gamma Source: UniProtKB
Cellular response to lipopolysaccharide Source: UniProtKB
Cellular response to mechanical stimulus Source: UniProtKB
Cellular response to organic substance Source: MGI
Cytokine-mediated signaling pathway Source: Reactome
Cytokine precursor processing Source: ARUK-UCL
Execution phase of apoptosis Source: GOC
Membrane hyperpolarization Source: Ensembl
Mitochondrial depolarization Source: Ensembl
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of interleukin-1 alpha production Source: Ensembl
Positive regulation of interleukin-1 beta production Source: UniProtKB
Positive regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Programmed necrotic cell death Source: Ensembl
Protein autoprocessing Source: UniProtKB
Proteolysis Source: UniProtKB
Purinergic nucleotide receptor signaling pathway Source: Reactome
Pyroptosis Source: UniProtKB
Regulation of apoptotic process Source: Reactome
Regulation of autophagy Source: Ensembl
Regulation of inflammatory response Source: UniProtKB
Response to ATP Source: Ensembl
Response to hypoxia Source: Ensembl
Signaling receptor ligand precursor processing Source: ARUK-UCL
Signal transduction Source: ProtInc
Toxin transport Source: Ensembl

Cell membrane; Cytoplasm

The two subunits are derived from the precursor sequence by an autocatalytic mechanism.
Ubiquitinated via 'Lys-11'-linked polyubiquitination. Deubiquitinated by USP8.
Cleavage in the interdomain linker region is required to induce pyroptosis.