Caspase-5

Function

Thiol protease that acts as a mediator of programmed cell death. Initiates pyroptosis, a programmed lytic cell death pathway through cleavage of Gasdermin-D (GSDMD): cleavage releases the N-terminal gasdermin moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis. Also mediates cleavage and maturation of IL18. Cleavage of GSDMD and IL18 is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4. During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation.

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

Gene Ontology · 13

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0072558 NLRP1 inflammasome complex
• GO:0004197 cysteine-type endopeptidase activity
• GO:0008234 cysteine-type peptidase activity
• GO:0006915 apoptotic process
• GO:0071260 cellular response to mechanical stimulus
• GO:0160075 non-canonical inflammasome complex assembly
• GO:0050729 positive regulation of inflammatory response
• GO:0043525 positive regulation of neuron apoptotic process
• GO:0051604 protein maturation
• GO:0006508 proteolysis
• GO:0021762 substantia nigra development

Drugs targeting this protein · 1

• EMRICASAN inhibitor

Related proteins · sequence + function similarity

• Caspase-12 0.92
• Caspase-4 0.91
• Caspase-12 0.91
• Caspase-12 0.90
• Caspase-13 0.89
• Caspase-4 0.89
• Caspase-12 0.89
• Caspase-4 0.88
• Inactive caspase-12 0.87
• Caspase-1 0.85
• Caspase-1 0.85
• Caspase-1 0.83

Co-cited proteins · studied together in the literature

• Caspase-4 5 shared papers
• Gasdermin-D 1 shared papers
• Caspase-1 3 shared papers
• Caspase-4 3 shared papers
• Caspase-1 2 shared papers
• Leukocyte elastase inhibitor C 1 shared papers
• Leukocyte elastase inhibitor B 1 shared papers
• NACHT, LRR and PYD domains-containing protein 2 1 shared papers
• Interleukin-18 1 shared papers
• Pyrin 1 shared papers
• Leukocyte elastase inhibitor 1 shared papers
• Leukocyte elastase inhibitor A 1 shared papers

Literature · 11 cited papers

• Recognition and maturation of IL-18 by caspase-4 noncanonical inflammasome. Nature · 2023
• SERPINB1-mediated checkpoint of inflammatory caspase activation. Nat. Immunol. · 2019
• Mechanism of membrane pore formation by human gasdermin-D. EMBO J. · 2018
• Inflammasome activation triggers caspase-1-mediated cleavage of cGAS to regulate responses to DNA virus infection. Immunity · 2017
• The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing. Cell Death Differ. · 2007
• Identification of a novel exon encoding the amino-terminus of the predominant caspase-5 variants. Biochem. Biophys. Res. Commun. · 2006
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Identification of a cysteine protease closely related to interleukin-1 beta-converting enzyme. Eur. J. Biochem. · 1996
• Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases. J. Biol. Chem. · 1995