ID CASP1_HUMAN Reviewed; 404 AA. AC P29466; B5MDZ1; Q53EY6; Q6DMQ1; Q6GSS3; Q6PI75; Q9UCN3; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 11-NOV-2015, entry version 179. DE RecName: Full=Caspase-1; DE Short=CASP-1; DE EC=3.4.22.36; DE AltName: Full=Interleukin-1 beta convertase; DE Short=IL-1BC; DE AltName: Full=Interleukin-1 beta-converting enzyme; DE Short=ICE; DE Short=IL-1 beta-converting enzyme; DE AltName: Full=p45; DE Contains: DE RecName: Full=Caspase-1 subunit p20; DE Contains: DE RecName: Full=Caspase-1 subunit p10; DE Flags: Precursor; GN Name=CASP1; Synonyms=IL1BC, IL1BCE; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), PARTIAL PROTEIN SEQUENCE, RP AND ACTIVE SITE. RX PubMed=1574116; DOI=10.1038/356768a0; RA Thornberry N.A., Bull H.G., Calaycay J.R., Chapman K.T., Howard A.D., RA Kostura M.J., Miller D.K., Molineaux S.M., Weidner J.R., Aunins J., RA Elliston K.O., Ayala J.M., Casano F.J., Chin J., Ding G.J.-F., RA Egger L.A., Gaffney E.P., Limjuco G., Palyha O.C., Raju M., RA Rolando A.M., Salley J.P., Yamin T.-T., Lee T.D., Shively J.E., RA McCross M., Mumford R.A., Schmidt J.A., Tocci M.J.; RT "A novel heterodimeric cysteine protease is required for interleukin-1 RT beta processing in monocytes."; RL Nature 356:768-774(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), AND PROTEIN SEQUENCE OF RP 120-142. RX PubMed=1373520; DOI=10.1126/science.1373520; RA Cerretti D.P., Kozlosky C.J., Mosley B., Nelson N., van Ness K., RA Greenstreet T.A., March C.J., Kronheim S.R., Druck T., RA Cannizzaro L.A., Huebner K., Black R.A.; RT "Molecular cloning of the interleukin-1 beta converting enzyme."; RL Science 256:97-100(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BETA; DELTA; EPSILON AND GAMMA), RP ALTERNATIVE SPLICING, AND FUNCTION. RX PubMed=7876192; DOI=10.1074/jbc.270.9.4312; RA Alnemri E.S., Fernandes-Alnemri T., Litwack G.; RT "Cloning and expression of four novel isoforms of human interleukin-1 RT beta converting enzyme with different apoptotic activities."; RL J. Biol. Chem. 270:4312-4317(1995). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GAMMA), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 4-404 (ISOFORM BETA). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-404 (ISOFORM ALPHA), FUNCTION, RP MUTAGENESIS OF CYS-285, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY. RX PubMed=15498465; DOI=10.1016/j.ygeno.2004.06.005; RA Feng Q., Li P., Leung P.C.K., Auersperg N.; RT "Caspase-1 zeta, a new splice variant of caspase-1 gene."; RL Genomics 84:587-591(2004). RN [8] RP PROTEIN SEQUENCE OF 120-142. RX PubMed=1321594; DOI=10.1016/0003-9861(92)90629-B; RA Kronheim S.R., Mumma A., Greenstreet T., Glackin P.J., Van Ness K., RA March C.J., Black R.A.; RT "Purification of interleukin-1 beta converting enzyme, the protease RT that cleaves the interleukin-1 beta precursor."; RL Arch. Biochem. Biophys. 296:698-703(1992). RN [9] RP INTERACTION WITH CARD18. RX PubMed=11051551; DOI=10.1016/S0092-8674(00)00108-2; RA Humke E.W., Shriver S.K., Starovasnik M.A., Fairbrother W.J., RA Dixit V.M.; RT "ICEBERG: a novel inhibitor of interleukin-1beta generation."; RL Cell 103:99-111(2000). RN [10] RP COMPONENT OF THE INFLAMMASOME. RX PubMed=15030775; DOI=10.1016/S1074-7613(04)00046-9; RA Agostini L., Martinon F., Burns K., McDermott M.F., Hawkins P.N., RA Tschopp J.; RT "NALP3 forms an IL-1beta-processing inflammasome with increased RT activity in Muckle-Wells autoinflammatory disorder."; RL Immunity 20:319-325(2004). RN [11] RP INTERACTION WITH CARD17. RX PubMed=15383541; DOI=10.1074/jbc.M407891200; RA Lamkanfi M., Denecker G., Kalai M., D'hondt K., Meeus A., Declercq W., RA Saelens X., Vandenabeele P.; RT "INCA, a novel human caspase recruitment domain protein that inhibits RT interleukin-1beta generation."; RL J. Biol. Chem. 279:51729-51738(2004). RN [12] RP INTERACTION WITH MEFV. RX PubMed=16785446; DOI=10.1073/pnas.0602081103; RA Chae J.J., Wood G., Masters S.L., Richard K., Park G., Smith B.J., RA Kastner D.L.; RT "The B30.2 domain of pyrin, the familial Mediterranean fever protein, RT interacts directly with caspase-1 to modulate IL-1beta production."; RL Proc. Natl. Acad. Sci. U.S.A. 103:9982-9987(2006). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT. RX PubMed=8044845; DOI=10.1016/0092-8674(94)90303-4; RA Walker N.P.C., Talanian R.V., Brady K.D., Dang L.C., Bump N.J., RA Ferenz C.R., Franklin S., Ghayur T., Hackett M.C., Hammill L.D., RA Herzog L., Hugunin M., Houy W., Mankovich J.A., McGuiness L., RA Orlewicz E., Paskind M., Pratt C.A., Reis P., Summani A., RA Terranova M., Welch J.P., Xiong L., Moeller A., Tracey D.E., Kamen R., RA Wong W.W.; RT "Crystal structure of the cysteine protease interleukin-1 beta- RT converting enzyme: a (p20/p10)2 homodimer."; RL Cell 78:343-352(1994). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.73 ANGSTROMS). RX PubMed=9190289; DOI=10.1016/S1074-5521(97)90258-1; RA Rano T.A., Timkey T., Peterson E.P., Rotonda J., Nicholson D.W., RA Becker J.W., Chapman K.T., Thornberry N.A.; RT "A combinatorial approach for determining protease specificities: RT application to interleukin-1beta converting enzyme (ICE)."; RL Chem. Biol. 4:149-155(1997). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH INHIBITORS. RX PubMed=9987822; RA Okamoto Y., Anan H., Nakai E., Morihira K., Yonetoku Y., Kurihara H., RA Sakashita H., Terai Y., Takeuchi M., Shibanuma T., Isomura Y.; RT "Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: RT synthesis, structure activity relationships and crystallographic study RT of the ICE-inhibitor complex."; RL Chem. Pharm. Bull. 47:11-21(1999). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 120-404 OF MUTANT ALA-285. RX PubMed=15296730; DOI=10.1016/j.str.2004.05.010; RA Romanowski M.J., Scheer J.M., O'Brien T., McDowell R.S.; RT "Crystal structures of a ligand-free and malonate-bound human caspase- RT 1: implications for the mechanism of substrate binding."; RL Structure 12:1361-1371(2004). CC -!- FUNCTION: Thiol protease that cleaves IL-1 beta between an Asp and CC an Ala, releasing the mature cytokine which is involved in a CC variety of inflammatory processes. Important for defense against CC pathogens. Cleaves and activates sterol regulatory element binding CC proteins (SREBPs). Can also promote apoptosis. CC {ECO:0000269|PubMed:15498465, ECO:0000269|PubMed:7876192}. CC -!- CATALYTIC ACTIVITY: Strict requirement for an Asp residue at CC position P1 and has a preferred cleavage sequence of Tyr-Val-Ala- CC Asp-|-. CC -!- ENZYME REGULATION: Specifically inhibited by the cowpox virus Crma CC protein. CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel CC arranged heterodimers, each one formed by a 20 kDa (p20) and a 10 CC kDa (p10) subunit. The p20 subunit can also form a heterodimer CC with the epsilon isoform which then has an inhibitory effect. May CC be a component of the inflammasome, a protein complex which also CC includes PYCARD, CARD8 and NALP2 and whose function would be the CC activation of proinflammatory caspases. Both the p10 and p20 CC subunits interact with MEFV. Interacts with CARD17/INCA and CC CARD18. {ECO:0000269|PubMed:11051551, ECO:0000269|PubMed:15383541, CC ECO:0000269|PubMed:16785446, ECO:0000269|PubMed:8044845, CC ECO:0000269|PubMed:9987822}. CC -!- INTERACTION: CC P09038:FGF2; NbExp=2; IntAct=EBI-516667, EBI-977447; CC P01583:IL1A; NbExp=3; IntAct=EBI-516667, EBI-1749782; CC Q9NPP4:NLRC4; NbExp=4; IntAct=EBI-516667, EBI-1222527; CC Q9ULZ3:PYCARD; NbExp=5; IntAct=EBI-516667, EBI-751215; CC Q08AM6:VAC14; NbExp=3; IntAct=EBI-516667, EBI-2107455; CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=Additional isoforms seem to exist.; CC Name=Alpha; CC IsoId=P29466-1; Sequence=Displayed; CC Name=Beta; CC IsoId=P29466-2; Sequence=VSP_000798; CC Name=Gamma; CC IsoId=P29466-3; Sequence=VSP_000799; CC Name=Delta; CC IsoId=P29466-4; Sequence=VSP_000799, VSP_000800; CC Note=Apoptosis inactive.; CC Name=Epsilon; CC IsoId=P29466-5; Sequence=VSP_000797; CC Note=Apoptosis inactive.; CC -!- TISSUE SPECIFICITY: Expressed in larger amounts in spleen and CC lung. Detected in liver, heart, small intestine, colon, thymus, CC prostate, skeletal muscle, peripheral blood leukocytes, kidney and CC testis. No expression in the brain. {ECO:0000269|PubMed:15498465}. CC -!- PTM: The two subunits are derived from the precursor sequence by CC an autocatalytic mechanism. CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 CARD domain. {ECO:0000255|PROSITE- CC ProRule:PRU00046}. CC -!- SEQUENCE CAUTION: CC Sequence=AAT72297.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAT72297.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/CASP1ID145ch11q22.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X65019; CAA46153.1; -; mRNA. DR EMBL; M87507; AAA66942.1; -; mRNA. DR EMBL; U13697; AAC50107.1; -; mRNA. DR EMBL; U13698; AAC50108.1; -; mRNA. DR EMBL; U13699; AAC50109.1; -; mRNA. DR EMBL; U13700; AAC50110.1; -; mRNA. DR EMBL; AK223503; BAD97223.1; -; mRNA. DR EMBL; AP001153; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC041689; AAH41689.1; -; mRNA. DR EMBL; BC062327; AAH62327.1; -; mRNA. DR EMBL; AY660536; AAT72297.1; ALT_SEQ; mRNA. DR CCDS; CCDS53704.1; -. [P29466-3] DR CCDS; CCDS8329.1; -. [P29466-2] DR CCDS; CCDS8330.1; -. [P29466-1] DR CCDS; CCDS8331.1; -. [P29466-4] DR CCDS; CCDS8332.1; -. [P29466-5] DR PIR; A54263; A42677. DR PIR; A56084; A56084. DR PIR; B56084; B56084. DR PIR; C56084; C56084. DR PIR; D56084; D56084. DR RefSeq; NP_001214.1; NM_001223.4. [P29466-2] DR RefSeq; NP_001244047.1; NM_001257118.2. [P29466-1] DR RefSeq; NP_001244048.1; NM_001257119.2. [P29466-2] DR RefSeq; NP_150634.1; NM_033292.3. [P29466-1] DR RefSeq; NP_150635.1; NM_033293.3. [P29466-3] DR RefSeq; NP_150636.1; NM_033294.3. [P29466-4] DR RefSeq; NP_150637.1; NM_033295.3. [P29466-5] DR UniGene; Hs.2490; -. DR PDB; 1BMQ; X-ray; 2.50 A; A=131-297, B=317-404. DR PDB; 1IBC; X-ray; 2.73 A; A=104-297, B=317-404. DR PDB; 1ICE; X-ray; 2.60 A; A=131-297, B=317-404. DR PDB; 1RWK; X-ray; 2.30 A; A=120-297, B=317-404. DR PDB; 1RWM; X-ray; 2.70 A; A=120-297, B=317-404. DR PDB; 1RWN; X-ray; 2.00 A; A=120-297, B=317-404. DR PDB; 1RWO; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 1RWP; X-ray; 2.20 A; A=120-297, B=317-404. DR PDB; 1RWV; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 1RWW; X-ray; 2.80 A; A=120-297, B=317-404. DR PDB; 1RWX; X-ray; 1.85 A; A=120-297, B=317-404. DR PDB; 1SC1; X-ray; 2.60 A; A=120-297, B=317-404. DR PDB; 1SC3; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 1SC4; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 2FQQ; X-ray; 3.30 A; A=120-297, B=317-404. DR PDB; 2H48; X-ray; 2.20 A; A=120-297, B=317-404. DR PDB; 2H4W; X-ray; 2.00 A; A=120-297, B=317-404. DR PDB; 2H4Y; X-ray; 1.90 A; A=120-297, B=317-404. DR PDB; 2H51; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 2H54; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 2HBQ; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 2HBR; X-ray; 2.20 A; A=120-297, B=317-404. DR PDB; 2HBY; X-ray; 2.10 A; A=120-297, B=317-404. DR PDB; 2HBZ; X-ray; 1.90 A; A=120-297, B=317-404. DR PDB; 3D6F; X-ray; 1.90 A; A=120-297, B=317-404. DR PDB; 3D6H; X-ray; 2.00 A; A=120-297, B=317-404. DR PDB; 3D6M; X-ray; 1.80 A; A=120-297, B=317-404. DR PDB; 3E4C; X-ray; 2.05 A; A/B=104-404. DR PDB; 3NS7; X-ray; 2.60 A; A=136-297, B=317-404. DR PDBsum; 1BMQ; -. DR PDBsum; 1IBC; -. DR PDBsum; 1ICE; -. DR PDBsum; 1RWK; -. DR PDBsum; 1RWM; -. DR PDBsum; 1RWN; -. DR PDBsum; 1RWO; -. DR PDBsum; 1RWP; -. DR PDBsum; 1RWV; -. DR PDBsum; 1RWW; -. DR PDBsum; 1RWX; -. DR PDBsum; 1SC1; -. DR PDBsum; 1SC3; -. DR PDBsum; 1SC4; -. DR PDBsum; 2FQQ; -. DR PDBsum; 2H48; -. DR PDBsum; 2H4W; -. DR PDBsum; 2H4Y; -. DR PDBsum; 2H51; -. DR PDBsum; 2H54; -. DR PDBsum; 2HBQ; -. DR PDBsum; 2HBR; -. DR PDBsum; 2HBY; -. DR PDBsum; 2HBZ; -. DR PDBsum; 3D6F; -. DR PDBsum; 3D6H; -. DR PDBsum; 3D6M; -. DR PDBsum; 3E4C; -. DR PDBsum; 3NS7; -. DR ProteinModelPortal; P29466; -. DR SMR; P29466; 2-89, 125-404. DR BioGrid; 107284; 34. DR DIP; DIP-175N; -. DR IntAct; P29466; 10. DR MINT; MINT-201196; -. DR STRING; 9606.ENSP00000410076; -. DR BindingDB; P29466; -. DR ChEMBL; CHEMBL4801; -. DR DrugBank; DB01017; Minocycline. DR GuidetoPHARMACOLOGY; 1617; -. DR MEROPS; C14.001; -. DR PhosphoSite; P29466; -. DR BioMuta; CASP1; -. DR DMDM; 266321; -. DR MaxQB; P29466; -. DR PaxDb; P29466; -. DR PRIDE; P29466; -. DR DNASU; 834; -. DR Ensembl; ENST00000353247; ENSP00000344132; ENSG00000137752. [P29466-5] DR Ensembl; ENST00000436863; ENSP00000410076; ENSG00000137752. [P29466-1] DR Ensembl; ENST00000446369; ENSP00000403260; ENSG00000137752. [P29466-4] DR Ensembl; ENST00000525825; ENSP00000434779; ENSG00000137752. [P29466-2] DR Ensembl; ENST00000526568; ENSP00000434250; ENSG00000137752. [P29466-3] DR Ensembl; ENST00000531166; ENSP00000434303; ENSG00000137752. [P29466-5] DR Ensembl; ENST00000533400; ENSP00000433138; ENSG00000137752. [P29466-1] DR Ensembl; ENST00000534497; ENSP00000436875; ENSG00000137752. [P29466-4] DR GeneID; 834; -. DR KEGG; hsa:834; -. DR UCSC; uc001pig.4; human. [P29466-3] DR UCSC; uc001pim.5; human. [P29466-1] DR UCSC; uc009yxi.4; human. [P29466-2] DR UCSC; uc021qpr.2; human. [P29466-4] DR UCSC; uc021qps.2; human. [P29466-5] DR CTD; 834; -. DR GeneCards; CASP1; -. DR HGNC; HGNC:1499; CASP1. DR HPA; CAB002685; -. DR HPA; HPA003056; -. DR MIM; 147678; gene. DR neXtProt; NX_P29466; -. DR PharmGKB; PA26083; -. DR eggNOG; KOG3573; Eukaryota. DR eggNOG; ENOG410ZQIE; LUCA. DR GeneTree; ENSGT00760000118912; -. DR HOVERGEN; HBG076981; -. DR InParanoid; P29466; -. DR KO; K01370; -. DR OMA; EDDAIKK; -. DR PhylomeDB; P29466; -. DR TreeFam; TF102023; -. DR BRENDA; 3.4.22.36; 2681. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-448706; Interleukin-1 processing. DR Reactome; R-HSA-844456; The NLRP3 inflammasome. DR Reactome; R-HSA-844615; The AIM2 inflammasome. DR Reactome; R-HSA-844623; The IPAF inflammasome. DR SABIO-RK; P29466; -. DR SignaLink; P29466; -. DR ChiTaRS; CASP1; human. DR EvolutionaryTrace; P29466; -. DR GeneWiki; Caspase_1; -. DR GenomeRNAi; 834; -. DR NextBio; 3460; -. DR PMAP-CutDB; P29466; -. DR PRO; PR:P29466; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P29466; -. DR CleanEx; HS_CASP1; -. DR ExpressionAtlas; P29466; baseline and differential. DR Genevisible; P29466; HS. DR GO; GO:0097169; C:AIM2 inflammasome complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; IEA:Ensembl. DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB. DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; TAS:ProtInc. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0004175; F:endopeptidase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:GOC. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0032611; P:interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl. DR GO; GO:0051882; P:mitochondrial depolarization; IEA:Ensembl. DR GO; GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEP:UniProtKB. DR GO; GO:0050717; P:positive regulation of interleukin-1 alpha secretion; IEA:Ensembl. DR GO; GO:0050718; P:positive regulation of interleukin-1 beta secretion; IEA:Ensembl. DR GO; GO:0097300; P:programmed necrotic cell death; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0070269; P:pyroptosis; IEA:Ensembl. DR GO; GO:0010506; P:regulation of autophagy; IEA:Ensembl. DR GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central. DR GO; GO:0033198; P:response to ATP; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:1901998; P:toxin transport; IEA:Ensembl. DR Gene3D; 1.10.533.10; -; 1. DR Gene3D; 3.40.50.1460; -; 1. DR InterPro; IPR001315; CARD. DR InterPro; IPR029030; Caspase-like_dom. DR InterPro; IPR011029; DEATH-like_dom. DR InterPro; IPR011600; Pept_C14_caspase. DR InterPro; IPR001309; Pept_C14_ICE_p20. DR InterPro; IPR016129; Pept_C14_ICE_p20_AS. DR InterPro; IPR002138; Pept_C14_p10. DR InterPro; IPR017350; Pept_C14A_Casp1-type. DR InterPro; IPR015917; Pept_C14A_p45_core. DR Pfam; PF00619; CARD; 1. DR Pfam; PF00656; Peptidase_C14; 1. DR PIRSF; PIRSF038001; Caspase_ICE; 1. DR PRINTS; PR00376; IL1BCENZYME. DR SMART; SM00114; CARD; 1. DR SMART; SM00115; CASc; 1. DR SUPFAM; SSF47986; SSF47986; 1. DR PROSITE; PS50209; CARD; 1. DR PROSITE; PS01122; CASPASE_CYS; 1. DR PROSITE; PS01121; CASPASE_HIS; 1. DR PROSITE; PS50207; CASPASE_P10; 1. DR PROSITE; PS50208; CASPASE_P20; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome; KW Cytoplasm; Direct protein sequencing; Hydrolase; Phosphoprotein; KW Polymorphism; Protease; Reference proteome; Thiol protease; Zymogen. FT PROPEP 1 119 FT /FTId=PRO_0000004521. FT CHAIN 120 297 Caspase-1 subunit p20. FT /FTId=PRO_0000004522. FT PROPEP 298 316 FT /FTId=PRO_0000004523. FT CHAIN 317 404 Caspase-1 subunit p10. FT /FTId=PRO_0000004524. FT DOMAIN 1 91 CARD. {ECO:0000255|PROSITE- FT ProRule:PRU00046}. FT ACT_SITE 237 237 {ECO:0000269|PubMed:1574116}. FT ACT_SITE 285 285 {ECO:0000269|PubMed:1574116}. FT MOD_RES 302 302 Phosphoserine. FT {ECO:0000250|UniProtKB:P29452}. FT VAR_SEQ 20 335 Missing (in isoform Epsilon). FT {ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000797. FT VAR_SEQ 20 112 Missing (in isoform Gamma and isoform FT Delta). {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000799. FT VAR_SEQ 92 112 Missing (in isoform Beta). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000798. FT VAR_SEQ 288 335 Missing (in isoform Delta). FT {ECO:0000303|PubMed:7876192}. FT /FTId=VSP_000800. FT VARIANT 15 15 R -> H (in dbSNP:rs1042743). FT /FTId=VAR_048615. FT MUTAGEN 285 285 C->A,S: Loss of activity. FT {ECO:0000269|PubMed:15498465}. FT CONFLICT 319 319 K -> R (in Ref. 4; BAD97223). FT {ECO:0000305}. FT CONFLICT 402 402 P -> L (in Ref. 4; BAD97223). FT {ECO:0000305}. FT TURN 129 132 {ECO:0000244|PDB:1SC3}. FT HELIX 138 147 {ECO:0000244|PDB:1SC3}. FT STRAND 148 150 {ECO:0000244|PDB:1SC3}. FT TURN 158 160 {ECO:0000244|PDB:1SC3}. FT STRAND 164 169 {ECO:0000244|PDB:1SC3}. FT STRAND 174 176 {ECO:0000244|PDB:1SC3}. FT HELIX 182 195 {ECO:0000244|PDB:1SC3}. FT STRAND 199 205 {ECO:0000244|PDB:1SC3}. FT HELIX 208 219 {ECO:0000244|PDB:1SC3}. FT HELIX 222 226 {ECO:0000244|PDB:1SC3}. FT STRAND 230 236 {ECO:0000244|PDB:1SC3}. FT STRAND 242 244 {ECO:0000244|PDB:1SC3}. FT STRAND 250 252 {ECO:0000244|PDB:1SC3}. FT STRAND 255 257 {ECO:0000244|PDB:1SC4}. FT HELIX 258 265 {ECO:0000244|PDB:1SC3}. FT TURN 267 269 {ECO:0000244|PDB:1SC3}. FT HELIX 271 273 {ECO:0000244|PDB:1SC3}. FT STRAND 278 283 {ECO:0000244|PDB:1SC3}. FT STRAND 287 289 {ECO:0000244|PDB:1SC3}. FT STRAND 291 298 {ECO:0000244|PDB:3E4C}. FT HELIX 316 319 {ECO:0000244|PDB:3E4C}. FT STRAND 326 333 {ECO:0000244|PDB:1SC3}. FT STRAND 340 342 {ECO:0000244|PDB:2H54}. FT TURN 343 345 {ECO:0000244|PDB:1SC3}. FT HELIX 348 360 {ECO:0000244|PDB:1SC3}. FT TURN 361 363 {ECO:0000244|PDB:1SC3}. FT HELIX 366 376 {ECO:0000244|PDB:1SC3}. FT STRAND 381 383 {ECO:0000244|PDB:1SC1}. FT STRAND 388 391 {ECO:0000244|PDB:1SC3}. FT STRAND 395 397 {ECO:0000244|PDB:1RWM}. SQ SEQUENCE 404 AA; 45159 MW; ABF33CF33CC71584 CRC64; MADKVLKEKR KLFIRSMGEG TINGLLDELL QTRVLNKEEM EKVKRENATV MDKTRALIDS VIPKGAQACQ ICITYICEED SYLAGTLGLS ADQTSGNYLN MQDSQGVLSS FPAPQAVQDN PAMPTSSGSE GNVKLCSLEE AQRIWKQKSA EIYPIMDKSS RTRLALIICN EEFDSIPRRT GAEVDITGMT MLLQNLGYSV DVKKNLTASD MTTELEAFAH RPEHKTSDST FLVFMSHGIR EGICGKKHSE QVPDILQLNA IFNMLNTKNC PSLKDKPKVI IIQACRGDSP GVVWFKDSVG VSGNLSLPTT EEFEDDAIKK AHIEKDFIAF CSSTPDNVSW RHPTMGSVFI GRLIEHMQEY ACSCDVEEIF RKVRFSFEQP DGRAQMPTTE RVTLTRCFYL FPGH //