Caspase-1

Details

Name
Caspase-1
Synonyms
  • 3.4.22.36
  • CASP-1
  • ICE
  • IL-1 beta-converting enzyme
  • IL-1BC
  • IL1BC
  • IL1BCE
  • Interleukin-1 beta convertase
  • Interleukin-1 beta-converting enzyme
  • p45
Gene Name
CASP1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000885|Caspase-1
MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDS
VIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDN
PAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRT
GAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIR
EGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVG
VSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEY
ACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH
Number of residues
404
Molecular Weight
45158.215
Theoretical pI
5.71
GO Classification
Functions
cysteine-type endopeptidase activator activity involved in apoptotic process / cysteine-type endopeptidase activity / endopeptidase activity
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / apoptotic process / cellular response to mechanical stimulus / cellular response to organic substance / innate immune response / interleukin-1 beta production / membrane hyperpolarization / mitochondrial depolarization / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of interleukin-1 alpha secretion / positive regulation of interleukin-1 beta secretion / programmed necrotic cell death / proteolysis / pyroptosis / regulation of autophagy / regulation of inflammatory response / response to ATP / response to hypoxia / response to lipopolysaccharide / signal transduction / toxin transport
Components
AIM2 inflammasome complex / cytoplasm / cytosol / extracellular region / IPAF inflammasome complex / mitochondrion / NLRP1 inflammasome complex / NLRP3 inflammasome complex
General Function
Endopeptidase activity
Specific Function
Thiol protease that cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Important for defense against pathogens. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Can also promote apoptosis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020459|Caspase-1 (CASP1)
ATGGCCGACAAGGTCCTGAAGGAGAAGAGAAAGCTGTTTATCCGTTCCATGGGTGAAGGT
ACAATAAATGGCTTACTGGATGAATTATTACAGACAAGGGTGCTGAACAAGGAAGAGATG
GAGAAAGTAAAACGTGAAAATGCTACAGTTATGGATAAGACCCGAGCTTTGATTGACTCC
GTTATTCCGAAAGGGGCACAGGCATGCCAAATTTGCATCACATACATTTGTGAAGAAGAC
AGTTACCTGGCAGGGACGCTGGGACTCTCAGCAGCTCCTCAGGCAGTGCAGGACAACCCA
GCTATGCCCACATCCTCAGGCTCAGAAGGGAATGTCAAGCTTTGCTCCCTAGAAGAAGCT
CAAAGGATATGGAAACAAAAGTCGGCAGAGATTTATCCAATAATGGACAAGTCAAGCCGC
ACACGTCTTGCTCTCATTATCTGCAATGAAGAATTTGACAGTATTCCTAGAAGAACTGGA
GCTGAGGTTGACATCACAGGCATGACAATGCTGCTACAAAATCTGGGGTACAGCGTAGAT
GTGAAAAAAAATCTCACTGCTTCGGACATGACTACAGAGCTGGAGGCATTTGCACACCGC
CCAGAGCACAAGACCTCTGACAGCACGTTCCTGGTGTTCATGTCTCATGGTATTCGGGAA
GGCATTTGTGGGAAGAAACACTCTGAGCAAGTCCCAGATATACTACAACTCAATGCAATC
TTTAACATGTTGAATACCAAGAACTGCCCAAGTTTGAAGGACAAACCGAAGGTGATCATC
ATCCAGGCCTGCCGTGGTGACAGCCCTGGTGTGGTGTGGTTTAAAGATTCAGTAGGAGTT
TCTGGAAACCTATCTTTACCAACTACAGAAGAGTTTGAGGATGATGCTATTAAGAAAGCC
CACATAGAGAAGGATTTTATCGCTTTCTGCTCTTCCACACCAGATAATGTTTCTTGGAGA
CATCCCACAATGGGCTCTGTTTTTATTGGAAGACTCATTGAACATATGCAAGAATATGCC
TGTTCCTGTGATGTGGAGGAAATTTTCCGCAAGGTTCGATTTTCATTTGAGCAGCCAGAT
GGTAGAGCGCAGATGCCCACCACTGAAAGAGTGACTTTGACAAGATGTTTCTACCTCTTC
CCAGGACATTAA
Chromosome Location
11
Locus
11q23
External Identifiers
ResourceLink
UniProtKB IDP29466
UniProtKB Entry NameCASP1_HUMAN
GenBank Protein ID33793
GenBank Gene IDX65019
GenAtlas IDCASP1
HGNC IDHGNC:1499
General References
  1. Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J, et al.: A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992 Apr 30;356(6372):768-74. [PubMed:1574116]
  2. Cerretti DP, Kozlosky CJ, Mosley B, Nelson N, Van Ness K, Greenstreet TA, March CJ, Kronheim SR, Druck T, Cannizzaro LA, et al.: Molecular cloning of the interleukin-1 beta converting enzyme. Science. 1992 Apr 3;256(5053):97-100. [PubMed:1373520]
  3. Alnemri ES, Fernandes-Alnemri T, Litwack G: Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. J Biol Chem. 1995 Mar 3;270(9):4312-7. [PubMed:7876192]
  4. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811]
  5. 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]
  6. Feng Q, Li P, Leung PC, Auersperg N: Caspase-1zeta, a new splice variant of the caspase-1 gene. Genomics. 2004 Sep;84(3):587-91. [PubMed:15498465]
  7. Kronheim SR, Mumma A, Greenstreet T, Glackin PJ, Van Ness K, March CJ, Black RA: Purification of interleukin-1 beta converting enzyme, the protease that cleaves the interleukin-1 beta precursor. Arch Biochem Biophys. 1992 Aug 1;296(2):698-703. [PubMed:1321594]
  8. Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM: ICEBERG: a novel inhibitor of interleukin-1beta generation. Cell. 2000 Sep 29;103(1):99-111. [PubMed:11051551]
  9. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J: NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity. 2004 Mar;20(3):319-25. [PubMed:15030775]
  10. Lamkanfi M, Denecker G, Kalai M, D'hondt K, Meeus A, Declercq W, Saelens X, Vandenabeele P: INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1beta generation. J Biol Chem. 2004 Dec 10;279(50):51729-38. Epub 2004 Sep 21. [PubMed:15383541]
  11. Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, Kastner DL: The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9982-7. Epub 2006 Jun 19. [PubMed:16785446]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  13. Walker NP, Talanian RV, Brady KD, Dang LC, Bump NJ, Ferenz CR, Franklin S, Ghayur T, Hackett MC, Hammill LD, et al.: Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: a (p20/p10)2 homodimer. Cell. 1994 Jul 29;78(2):343-52. [PubMed:8044845]
  14. Rano TA, Timkey T, Peterson EP, Rotonda J, Nicholson DW, Becker JW, Chapman KT, Thornberry NA: A combinatorial approach for determining protease specificities: application to interleukin-1beta converting enzyme (ICE). Chem Biol. 1997 Feb;4(2):149-55. [PubMed:9190289]
  15. Okamoto Y, Anan H, Nakai E, Morihira K, Yonetoku Y, Kurihara H, Sakashita H, Terai Y, Takeuchi M, Shibanuma T, Isomura Y: Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex. Chem Pharm Bull (Tokyo). 1999 Jan;47(1):11-21. [PubMed:9987822]
  16. Romanowski MJ, Scheer JM, O'Brien T, McDowell RS: Crystal structures of a ligand-free and malonate-bound human caspase-1: implications for the mechanism of substrate binding. Structure. 2004 Aug;12(8):1361-71. [PubMed:15296730]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01017Minocyclineapproved, investigationalunknownnegative modulatorDetails
DB04875PralnacasaninvestigationalunknownDetails
DB05301LAX-101investigationalunknownDetails
DB05408EmricasaninvestigationalunknownDetails
DB05507VX-765investigationalunknownDetails
DB077331-METHYL-3-TRIFLUOROMETHYL-1H-THIENO[2,3-C]PYRAZOLE-5-CARBOXYLIC ACID (2-MERCAPTO-ETHYL)-AMIDEexperimentalunknownDetails
DB07744Z-Val-Ala-Asp fluoromethyl ketoneexperimentalunknownDetails
DB079163-{6-[(8-HYDROXY-QUINOLINE-2-CARBONYL)-AMINO]-2-THIOPHEN-2-YL-HEXANOYLAMINO}-4-OXO-BUTYRI ACIDexperimentalunknownDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknowninhibitordownregulatorDetails