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Identification
HMDB Protein ID HMDBP14454
Secondary Accession Numbers None
Name Caspase-1
Synonyms
  1. CASP-1
  2. Interleukin-1 beta convertase
  3. Interleukin-1 beta-converting enzyme
  4. p45
  5. IL-1BC
  6. ICE
  7. IL-1 beta-converting enzyme
Gene Name CASP1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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:21147462, PubMed:32109412). 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:21147462). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:21147462). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:32109412). 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:32109412). 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 (By similarity).
Pathways
  • Amyotrophic lateral sclerosis
  • C-type lectin receptor signaling pathway
  • Coronavirus disease - COVID-19
  • Cytosolic DNA-sensing pathway
  • Influenza A
  • Legionellosis
  • Lipid and atherosclerosis
  • Necroptosis
  • Neutrophil extracellular trap formation
  • NOD-like receptor signaling pathway
  • Pertussis
  • Salmonella infection
  • Yersinia infection
Reactions Not Available
GO Classification
Biological Process
regulation of inflammatory response
positive regulation of apoptotic process
protein autoprocessing
response to bacterium
response to lipopolysaccharide
pyroptosis
response to ATP
positive regulation of cytokine production
regulation of autophagy
cellular response to organic substance
response to drug
toxin transport
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
cellular response to lipopolysaccharide
memory
cytokine precursor processing
membrane hyperpolarization
mitochondrial depolarization
positive regulation of interleukin-1 alpha production
positive regulation of tumor necrosis factor-mediated signaling pathway
programmed necrotic cell death
signaling receptor ligand precursor processing
execution phase of apoptosis
proteolysis
positive regulation of I-kappaB kinase/NF-kappaB cascade
myoblast fusion
positive regulation of circadian sleep/wake cycle, non-REM sleep
cellular response to mechanical stimulus
response to organic cyclic compound
microglial cell activation
positive regulation of interleukin-1 beta production
protein processing
response to hypoxia
cellular response to interferon-gamma
Cellular Component
cytosol
protein-containing complex
cytoplasm
mitochondrion
NLRP1 inflammasome complex
plasma membrane
nucleus
AIM2 inflammasome complex
IPAF inflammasome complex
NLRP3 inflammasome complex
extracellular region
protease inhibitor complex
neuron projection
Molecular Function
endopeptidase activity
CARD domain binding
peptidase activity
cysteine-type endopeptidase activity
scaffold protein binding
kinase binding
cysteine-type endopeptidase activity involved in apoptotic signaling pathway
identical protein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 402
Molecular Weight 45640.025
Theoretical pI 6.04
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P29452
UniProtKB/Swiss-Prot Entry Name CASP1_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001. [PubMed:21183079 ]
  3. Choi YJ, Kim S, Choi Y, Nielsen TB, Yan J, Lu A, Ruan J, Lee HR, Wu H, Spellberg B, Jung JU: SERPINB1-mediated checkpoint of inflammatory caspase activation. Nat Immunol. 2019 Mar;20(3):276-287. doi: 10.1038/s41590-018-0303-z. Epub 2019 Jan 28. [PubMed:30692621 ]
  4. Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee KA, Yang V, Aguiar M, Kornhauser J, Jia X, Ren J, Beausoleil SA, Silva JC, Vemulapalli V, Bedford MT, Comb MJ: Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics. 2014 Jan;13(1):372-87. doi: 10.1074/mcp.O113.027870. Epub 2013 Oct 15. [PubMed:24129315 ]
  5. Wang Y, Ning X, Gao P, Wu S, Sha M, Lv M, Zhou X, Gao J, Fang R, Meng G, Su X, Jiang Z: Inflammasome Activation Triggers Caspase-1-Mediated Cleavage of cGAS to Regulate Responses to DNA Virus Infection. Immunity. 2017 Mar 21;46(3):393-404. doi: 10.1016/j.immuni.2017.02.011. Epub 2017 Mar 14. [PubMed:28314590 ]
  6. Nett MA, Cerretti DP, Berson DR, Seavitt J, Gilbert DJ, Jenkins NA, Copeland NG, Black RA, Chaplin DD: Molecular cloning of the murine IL-1 beta converting enzyme cDNA. J Immunol. 1992 Nov 15;149(10):3254-9. [PubMed:1431103 ]
  7. Molineaux SM, Casano FJ, Rolando AM, Peterson EP, Limjuco G, Chin J, Griffin PR, Calaycay JR, Ding GJ, Yamin TT, et al.: Interleukin 1 beta (IL-1 beta) processing in murine macrophages requires a structurally conserved homologue of human IL-1 beta converting enzyme. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1809-13. doi: 10.1073/pnas.90.5.1809. [PubMed:8446594 ]
  8. Casano FJ, Rolando AM, Mudgett JS, Molineaux SM: The structure and complete nucleotide sequence of the murine gene encoding interleukin-1 beta converting enzyme (ICE). Genomics. 1994 Apr;20(3):474-81. doi: 10.1006/geno.1994.1203. [PubMed:8034321 ]
  9. Broz P, von Moltke J, Jones JW, Vance RE, Monack DM: Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. Cell Host Microbe. 2010 Dec 16;8(6):471-83. doi: 10.1016/j.chom.2010.11.007. [PubMed:21147462 ]
  10. Wang K, Sun Q, Zhong X, Zeng M, Zeng H, Shi X, Li Z, Wang Y, Zhao Q, Shao F, Ding J: Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis. Cell. 2020 Mar 5;180(5):941-955.e20. doi: 10.1016/j.cell.2020.02.002. Epub 2020 Feb 27. [PubMed:32109412 ]