Caspase-1 (CASP1)
The protein contains 404 amino acids for an estimated molecular weight of 45159 Da.
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, rende (updated: June 2, 2021)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs1042743 |
Biological Process
Activation of cysteine-type endopeptidase activity involved in apoptotic process
Apoptotic process
Cellular response to cytokine stimulus
Cellular response to interferon-gamma
Cellular response to lipopolysaccharide
Cellular response to mechanical stimulus
Cellular response to organic substance
Cytokine precursor processing
Cytokine-mediated signaling pathway
Execution phase of apoptosis
Interleukin-1 beta production
Membrane hyperpolarization
Mitochondrial depolarization
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of interleukin-1 alpha production
Positive regulation of interleukin-1 beta production
Positive regulation of interleukin-1 beta secretion
Positive regulation of tumor necrosis factor-mediated signaling pathway
Programmed necrotic cell death
Protein autoprocessing
Proteolysis
Purinergic nucleotide receptor signaling pathway
Pyroptosis
Regulation of apoptotic process
Regulation of autophagy
Regulation of inflammatory response
Response to ATP
Response to hypoxia
Signal transduction
Signaling receptor ligand precursor processing
Toxin transport
Cellular Component
AIM2 inflammasome complex
Cytoplasm
Cytosol
Extracellular region
IPAF inflammasome complex
Mitochondrion
NLRP1 inflammasome complex
NLRP3 inflammasome complex
Plasma membrane
Protease inhibitor complex
Protein-containing complex
Molecular Function
CARD domain binding
Cysteine-type endopeptidase activator activity involved in apoptotic process
Cysteine-type endopeptidase activity
Cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Cysteine-type endopeptidase activity involved in execution phase of apoptosis
Endopeptidase activity
Identical protein binding
Kinase binding
The reference OMIM entry for this protein is 147678
Caspase 1, apoptosis-related cysteine protease; casp1
Interleukin 1-beta convertase; il1bc
Il1b-convertase
Il1b-converting enzyme; ice
DESCRIPTION
Caspase-1 is a cysteine protease that regulates inflammatory processes through its capacity to process and activate the interleukin-1-beta (IL1B; 147720), IL18 (600953), and IL33 (608678) precursor proteins. IL1B and IL18 are potent proinflammatory cytokines, and IL33 promotes responses mediated by type-2 helper T (Th2) cells (Keller et al., 2008).CLONING
Thornberry et al. (1992) purified ICE from the cytosol of the THP.1 human monocytic cell line and found that the active protease was made up of 2 peptides, which they called p20 and p10 based on their apparent molecular masses by SDS-PAGE. By PCR of a THP.1 cDNA library using primers based on tryptic peptide sequences of p20 and p10, followed by screening the same cDNA library, Thornberry et al. (1992) obtained 2 full-length ICE cDNAs that differed in the length of their 3-prime UTRs. The deduced 404-amino acid proprotein has a 119-amino acid propeptide that lacks characteristics of a hydrophobic signal sequence, followed by the p20 sequence, which ends in asp297, a 19-residue spacer, and the C-terminal p10 sequence, which ends in his404. The p20 sequence contains the catalytic cysteine, cys285. Neither the propeptide nor the spacer sequence were found in mature active ICE. Northern blot analysis revealed transcripts of 0.5, 1.6, and 2.3 kb in THP.1 cells, as well as in human neutrophils, T-lymphocytes, and the Raji B-lymphoblastoid cell line. The ICE proprotein had an apparent molecular mass of 45 kD following in vitro transcription and translation. Cerretti et al. (1992) cloned ICE from a human peripheral blood neutrophil cDNA library. Northern blot analysis of human tissues and cells detected a major transcript of about 1.9 kb in peripheral blood monocytes, lymphocytes, and neutrophils, resting and activated T lymphocytes, placenta, and a B-lymphoblastoid cell line, but not in HepG2 or Raji cell lines. Minor transcripts of 2.5 and 0.5 were also observed in some samples. Feng et al. (2004) noted that 5 alternatively spliced variants of CASP1 have been identified. The longest isoform is CASP1-alpha. Feng et al. (2004) cloned another CASP1 isoform, which they named CASP1-zeta, from an ovarian surface epithelial cell cDNA library. The CASP1-zeta transcript is identical to CASP1-alpha except for a 79-nucleotide deletion in the prodomain coding region. The deduced CASP1-zeta protein lacks 39 N-terminal amino acids compared with procaspase-1-alpha. This deleted region comprises the caspase-activating recruitment domain (CARD) required for interactions between caspases and other proteins. Secondary structure analysis of the CASP1-zeta CARD predicted the truncation of 2 alpha helices and part of the third compared with full-length procaspase-1-alpha. RT-PCR detected CASP1-zeta expression in many, but not all, adult human tissues. Humke et al. (1998) identified a cDNA encoding a novel caspase that they designated ERICE (evolutionarily related ICE), or caspase-13 (CASP13). Koenig et al. (2001) presented evidence that the sequence reported by Humke et al. (1998) was not of human origin, but represented a bovine gene.GENE FUNCTION
Thornberry et al. (1992) confirmed that ICE functions as cysteine protease, and they described the design of potent peptide aldehyde inhibitors. Selective inhibition of the enzyme in human blood monocytes blocked production of mature IL1B, indicating that it is a potential therapeutic target. Cerretti et al. (1992) demonst ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 147678 was added.
June 7, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 22, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 22, 2019: Protein entry updated
Automatic update: model status changed
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).