lmmol · Proteins

Caspase-1

UniProt P29466 Organism Homo sapiens Gene CASP1, IL1BC, IL1BCE EC 3.4.22.36

Also known as: CASP1, IL1BC, IL1BCE

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. 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. Cleaves a tetrapeptide after an Asp residue at position P1. Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD. 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. Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair. Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive. In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly.

Classification

Family (Pfam)
PF00619 CARD, PF00656 Peptidase_C14
InterPro
CARD, Caspase-like_dom_sf, Caspase_cys_AS, Caspase_his_AS, DEATH-like_dom_sf, Pept_C14, Pept_C14_caspase, Pept_C14_p10, Pept_C14_p20, Pept_C14A
Functional cluster
Immunoglobulin & Immune-Response Proteins

Experimental structures · PDB · 42

A predicted model is available from AlphaFold.

Gene Ontology · 43

Drugs targeting this protein · 3

Neighborhood · nearest proteins

CASP1CASP1CASP1CASP1CARD17CPXV207CARD18
Nearest neighbours of Caspase-1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 31 cited papers

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