Caspase 1
| Caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) |
PDB rendering based on 1bmq. |
| Available structures |
| PDB |
1BMQ, 1IBC, 1ICE, 1RWK, 1RWM, 1RWN, 1RWO, 1RWP, 1RWV, 1RWW, 1RWX, 1SC1, 1SC3, 1SC4, 2FQQ, 2H48, 2H4W, 2H4Y, 2H51, 2H54, 2HBQ, 2HBR, 2HBY, 2HBZ, 3D6F, 3D6H, 3D6M, 3E4C |
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| Identifiers |
| Symbols |
CASP1; ICE; IL1BC; P45 |
| External IDs |
OMIM: 147678 MGI: 96544 HomoloGene: 7653 GeneCards: CASP1 Gene |
| EC number |
3.4.22.36 |
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| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
834 |
12362 |
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| Ensembl |
ENSG00000137752 |
ENSMUSG00000025888 |
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| UniProt |
P29466 |
P29452 |
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| RefSeq (mRNA) |
NM_001223.3 |
NM_009807.2 |
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| RefSeq (protein) |
NP_001214.1 |
NP_033937.2 |
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| Location (UCSC) |
Chr 11:
104.9 – 104.97 Mb |
Chr 9:
5.3 – 5.31 Mb |
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| PubMed search |
[1] |
[2] |
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Caspase 1 is an enzyme that proteolytically cleaves other proteins, such as the precursor forms of the inflammatory cytokines interleukin 1-β and interleukin 18, into active mature peptides.[1][2] It belongs to a family of cysteine proteases known as caspases that always cleave proteins following an aspartic acid residue.[3] Caspase 1 is produced as a zymogen that is cleaved into 20 kDa (p20) and 10 kDa (p10) subunits that become part of the active enzyme. Active caspase 1 contains two heterodimers of p20 and p10. It interacts with another CARD domain containing protein called PYCARD (or ASC) and is involved in inflammasome formation and activation of inflammatory processes.[4]
Caspase 1 has been shown to induce cell necrosis or pyroptosis and may function in various developmental stages. Studies of a similar protein in mouse suggest a role in the pathogenesis of Huntington's disease. Alternative splicing of the gene results in five transcript variants encoding distinct isoforms.[5]
Interactions
Caspase 1 has been shown to interact with NLRC4.[6][7]
See also
References
- ^ Thornberry N, Bull H, Calaycay J, et al. (1992). "A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes". Nature 356 (6372): 768–74. doi:10.1038/356768a0. PMID 1574116.
- ^ Cerretti DP, Kozlosky CJ, Mosley B, et al. (1992). "Molecular cloning of the interleukin-1 beta converting enzyme". Science 256 (5053): 97–100. doi:10.1126/science.1373520. PMID 1373520.
- ^ Black RA, Kronheim SR, Merriam JE, March CJ, Hopp TP (1989). "A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta". J Biol Chem 264 (10): 5323–5326. PMID 2784432.
- ^ Mariathasan S, Newton K, Monack D, Vucic D, French D, Lee W, Roose-Girma M, Erickson S, Dixit V (2004). "Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf". Nature 430 (6996): 213–8. doi:10.1038/nature02664. PMID 15190255.
- ^ "Entrez Gene: CASP1 caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=834.
- ^ Damiano, Jason S; Oliveira Vasco, Welsh Kate, Reed John C (Jul. 2004). "Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses". Biochem. J. (England) 381 (Pt 1): 213–9. doi:10.1042/BJ20031506. PMC 1133779. PMID 15107016. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1133779.
- ^ Damiano, J S; Stehlik C, Pio F, Godzik A, Reed J C (Jul. 2001). "CLAN, a novel human CED-4-like gene". Genomics (United States) 75 (1–3): 77–83. doi:10.1006/geno.2001.6579. ISSN 0888-7543. PMID 11472070.
External links
- The MEROPS online database for peptidases and their inhibitors: C14.001
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PDB gallery
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1bmq: CRYSTAL STRUCTURE OF THE COMPLEX OF INTERLEUKIN-1BETA CONVERTING ENZYME (ICE) WITH A PEPTIDE BASED INHIBITOR, (3S )-N-METHANESULFONYL-3-({1-[N-(2-NAPHTOYL)-L-VALYL]-L-PROLYL }AMINO)-4-OXOBUTANAMIDE
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1ibc: CRYSTAL STRUCTURE OF INHIBITED INTERLEUKIN-1BETA CONVERTING ENZYME
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1ice: STRUCTURE AND MECHANISM OF INTERLEUKIN-1BETA CONVERTING ENZYME
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1rwk: Crystal structure of human caspase-1 in complex with 3-(2-mercapto-acetylamino)-4-oxo-pentanoic acid
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1rwm: Crystal structure of human caspase-1 in complex with 4-oxo-3-[2-(5-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-thiophen-2-yl)-acetylamino]-pentanoic acid
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1rwn: Crystal structure of human caspase-1 in complex with 3-{2-ethyl-6-[4-(quinoxalin-2-ylamino)-benzoylamino]-hexanoylamino}-4-oxo-butyric acid
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1rwo: Crystal structure of human caspase-1 in complex with 4-oxo-3-{6-[4-(quinoxalin-2-ylamino)-benzoylamino]-2-thiophen-2-yl-hexanoylamino}-pentanoic acid
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1rwp: Crystal structure of human caspase-1 in complex with 3-{6-[(8-hydroxy-quinoline-2-carbonyl)-amino]-2-thiophen-2-yl-hexanoylamino}-4-oxo-butyric acid
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1rwv: Crystal structure of human caspase-1 in complex with 5-[5-(1-carboxymethyl-2-oxo-propylcarbamoyl)-5-phenyl-pentylsulfamoyl]-2-hydroxy-benzoic acid
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1rww: Crystal structure of human caspase-1 in complex with 4-oxo-3-[(6-{[4-(quinoxalin-2-ylamino)-benzoylamino]-methyl}-pyridine-3-carbonyl)-amino]-butyric acid
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1rwx: Crystal structure of human caspase-1 in complex with 4-oxo-3-{6-[4-(quinoxalin-2-yloxy)-benzoylamino]-2-thiophen-2-yl-hexanoylamino}-butyric acid
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1sc1: Crystal structure of an active-site ligand-free form of the human caspase-1 C285A mutant
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1sc3: Crystal structure of the human caspase-1 C285A mutant in complex with malonate
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1sc4: Crystal structure of the human caspase-1 C285A mutant after removal of malonate
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2fqq: Crystal structure of human caspase-1 (Cys285->Ala, Cys362->Ala, Cys364->Ala, Cys397->Ala) in complex with 1-methyl-3-trifluoromethyl-1H-thieno[2,3-c]pyrazole-5-carboxylic acid (2-mercapto-ethyl)-amide
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2h48: Crystal structure of human caspase-1 (Cys362->Ala, Cys364->Ala, Cys397->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)
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2hbq: Crystal structure of wildtype human caspase-1 in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)
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2hbr: Crystal structure of human caspase-1 (Arg286->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)
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2hby: Crystal structure of human caspase-1 (Glu390->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)
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2hbz: Crystal structure of human caspase-1 (Arg286->Ala, Glu390->Ala) in complex with 3-[2-(2-benzyloxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-4-oxo-pentanoic acid (z-VAD-FMK)
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| Caspase |
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| Fruit-derived |
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| Calpain |
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| Cathepsin |
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| Other |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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