Caspase-1

Function

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:15498465, PubMed:1574116, PubMed:26375003, PubMed:32051255, PubMed:37993714, PubMed:7876192, PubMed:9334240). Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory 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:15326478, PubMed:15498465, PubMed:1574116, PubMed:32051255, PubMed:7876192). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:15498465, PubMed:1574116, PubMed:7876192). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:26375003). In contrast to cleavage of interleukin 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). Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:22464733). 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.

Post-translational modifications

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.

Sequence similarities

Belongs to the peptidase C14A family.

Tissue specificity

Expressed in larger amounts in spleen and lung. Detected in liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney and testis. No expression in the brain.

Cellular localization

• Cytoplasm
• Cell membrane

Alternative names

• IL1BC
• IL1BCE
• IL1BCE
• IL1BC
• CASP1
• Caspase-1
• CASP-1
• Interleukin-1 beta convertase
• Interleukin-1 beta-converting enzyme
• p45
• IL-1BC
• ICE
• IL-1 beta-converting enzyme

Database links

• entrezGene:834
• omim:147678
• swissprot:P29466

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

• Oncology

Molecular weight

45159Da