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Caspase-1

NameCaspase-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 NameCASP1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000885|Caspase-1
MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDS
VIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDN
PAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRT
GAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIR
EGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVG
VSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEY
ACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH
Number of residues404
Molecular Weight45158.215
Theoretical pI5.71
GO Classification
Functions
  • cysteine-type endopeptidase activator activity involved in apoptotic process
  • endopeptidase activity
  • cysteine-type endopeptidase activity
Processes
  • mitochondrial depolarization
  • toxin transport
  • regulation of autophagy
  • programmed necrotic cell death
  • cellular response to mechanical stimulus
  • apoptotic process
  • pyroptosis
  • response to hypoxia
  • regulation of inflammatory response
  • response to lipopolysaccharide
  • positive regulation of interleukin-1 alpha secretion
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • signal transduction
  • response to ATP
  • cellular response to organic substance
  • proteolysis
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • positive regulation of interleukin-1 beta secretion
  • membrane hyperpolarization
  • interleukin-1 beta production
  • innate immune response
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
Components
  • NLRP3 inflammasome complex
  • NLRP1 inflammasome complex
  • AIM2 inflammasome complex
  • IPAF inflammasome complex
  • cytoplasm
  • mitochondrion
  • extracellular region
  • cytosol
General FunctionEndopeptidase activity
Specific FunctionThiol 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 RegionsNot Available
GenBank Protein ID33793
UniProtKB IDP29466
UniProtKB Entry NameCASP1_HUMAN
Cellular LocationCytoplasm
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
GenBank Gene IDX65019
GeneCard IDNot Available
GenAtlas IDCASP1
HGNC IDHGNC:1499
Chromosome Location11
Locus11q23
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. 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. 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. 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. 16554811
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  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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 15296730