ID CASP1_MOUSE Reviewed; 402 AA.
AC P29452;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 27-MAR-2024, entry version 214.
DE RecName: Full=Caspase-1;
DE Short=CASP-1;
DE EC=3.4.22.36 {ECO:0000269|PubMed:18667412, ECO:0000269|PubMed:21147462, ECO:0000269|PubMed:35705808};
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 {ECO:0000305|PubMed:32109412};
DE Contains:
DE RecName: Full=Caspase-1 subunit p10 {ECO:0000305|PubMed:32109412};
DE Flags: Precursor;
GN Name=Casp1; Synonyms=Il1bc;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=1431103;
RA Nett-Fiordalisi M.A., Cerretti D.P., Berson D.R., Gilbert D.J.,
RA Jenkins N.A., Copeland N.G., Black R.A., Chaplin D.D.;
RT "Molecular cloning of the murine IL-1 beta converting enzyme cDNA.";
RL J. Immunol. 149:3254-3259(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8446594; DOI=10.1073/pnas.90.5.1809;
RA Molineaux S.M., Casano F.J., Rolando A.M., Peterson E.P., Limjuco G.,
RA Chin J., Griffin P.R., Calaycay J.R., Ding G.J.-F., Yamin T.-T.,
RA Palyha O.C., Luell S., Fletcher D., Miller D.K., Howard A.D.,
RA Thornberry N.A., Kostura M.J.;
RT "Interleukin 1 beta (IL-1 beta) processing in murine macrophages requires a
RT structurally conserved homologue of human IL-1 beta converting enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:1809-1813(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129;
RX PubMed=8034321; DOI=10.1006/geno.1994.1203;
RA Casano F.J., Rolando A.M., Mudgett J.S., Molineaux S.M.;
RT "The structure and complete nucleotide sequence of the murine gene encoding
RT interleukin-1 beta converting enzyme (ICE).";
RL Genomics 20:474-481(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP CHARACTERIZATION.
RC STRAIN=C3H/An;
RX PubMed=9038361; DOI=10.1016/s0014-5793(97)00026-4;
RA van de Craen M., Vandenabeele P., Declercq W., van den Brande I.,
RA van Loo G., Molemans F., Schotte P., van Criekinge W., Beyaert R.,
RA Fiers W.;
RT "Characterization of seven murine caspase family members.";
RL FEBS Lett. 403:61-69(1997).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18667412; DOI=10.1074/mcp.m800132-mcp200;
RA Lamkanfi M., Kanneganti T.D., Van Damme P., Vanden Berghe T.,
RA Vanoverberghe I., Vandekerckhove J., Vandenabeele P., Gevaert K., Nunez G.;
RT "Targeted peptidecentric proteomics reveals caspase-7 as a substrate of the
RT caspase-1 inflammasomes.";
RL Mol. Cell. Proteomics 7:2350-2363(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE,
RP ACTIVE SITE, AND MUTAGENESIS OF ASP-103; ASP-122; CYS-284;
RP 296-ASP--ASP-314; ASP-296 AND 313-ASP-ASP-314.
RX PubMed=21147462; DOI=10.1016/j.chom.2010.11.007;
RA Broz P., von Moltke J., Jones J.W., Vance R.E., Monack D.M.;
RT "Differential requirement for Caspase-1 autoproteolysis in pathogen-induced
RT cell death and cytokine processing.";
RL Cell Host Microbe 8:471-483(2010).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22464733; DOI=10.1016/j.molcel.2012.02.016;
RA Erener S., Petrilli V., Kassner I., Minotti R., Castillo R., Santoro R.,
RA Hassa P.O., Tschopp J., Hottiger M.O.;
RT "Inflammasome-activated caspase 7 cleaves PARP1 to enhance the expression
RT of a subset of NF-kappaB target genes.";
RL Mol. Cell 46:200-211(2012).
RN [10]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-343, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28314590; DOI=10.1016/j.immuni.2017.02.011;
RA Wang Y., Ning X., Gao P., Wu S., Sha M., Lv M., Zhou X., Gao J., Fang R.,
RA Meng G., Su X., Jiang Z.;
RT "Inflammasome activation triggers caspase-1-mediated cleavage of cGAS to
RT regulate responses to DNA virus infection.";
RL Immunity 46:393-404(2017).
RN [12]
RP FUNCTION, AND INTERACTION WITH SERPINB1A; SERPINB1B AND SERPINB1C.
RX PubMed=30692621; DOI=10.1038/s41590-018-0303-z;
RA Choi Y.J., Kim S., Choi Y., Nielsen T.B., Yan J., Lu A., Ruan J., Lee H.R.,
RA Wu H., Spellberg B., Jung J.U.;
RT "SERPINB1-mediated checkpoint of inflammatory caspase activation.";
RL Nat. Immunol. 20:276-287(2019).
RN [13]
RP FUNCTION, SUBUNIT, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF
RP 102-GLU--ASP-122 AND ILE-316.
RX PubMed=32109412; DOI=10.1016/j.cell.2020.02.002;
RA Wang K., Sun Q., Zhong X., Zeng M., Zeng H., Shi X., Li Z., Wang Y.,
RA Zhao Q., Shao F., Ding J.;
RT "Structural mechanism for GSDMD targeting by autoprocessed caspases in
RT pyroptosis.";
RL Cell 180:941-955(2020).
RN [14]
RP IDENTIFICATION IN THE AIM2 PANOPTOSOME COMPLEX.
RX PubMed=34471287; DOI=10.1038/s41586-021-03875-8;
RA Lee S., Karki R., Wang Y., Nguyen L.N., Kalathur R.C., Kanneganti T.D.;
RT "AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host
RT defence.";
RL Nature 597:415-419(2021).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=35705808; DOI=10.1038/s41586-022-04825-8;
RA Nozaki K., Maltez V.I., Rayamajhi M., Tubbs A.L., Mitchell J.E.,
RA Lacey C.A., Harvest C.K., Li L., Nash W.T., Larson H.N., McGlaughon B.D.,
RA Moorman N.J., Brown M.G., Whitmire J.K., Miao E.A.;
RT "Caspase-7 activates ASM to repair gasdermin and perforin pores.";
RL Nature 0:0-0(2022).
CC -!- FUNCTION: Thiol protease involved in a variety of inflammatory
CC processes by proteolytically cleaving other proteins, such as the
CC precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and
CC interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D
CC (GSDMD), into active mature peptides (PubMed:21147462,
CC PubMed:32109412). Plays a key role in cell immunity as an inflammatory
CC response initiator: once activated through formation of an inflammasome
CC complex, it initiates a pro-inflammatory response through the cleavage
CC of the two inflammatory cytokines IL1B and IL18, releasing the mature
CC cytokines which are involved in a variety of inflammatory processes
CC (PubMed:21147462). Cleaves a tetrapeptide after an Asp residue at
CC position P1 (PubMed:21147462). Also initiates pyroptosis, a programmed
CC lytic cell death pathway, through cleavage of GSDMD (PubMed:32109412).
CC In contrast to cleavage of interleukin IL1B, recognition and cleavage
CC of GSDMD is not strictly dependent on the consensus cleavage site but
CC depends on an exosite interface on CASP1 that recognizes and binds the
CC Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412). Cleaves and
CC activates CASP7 in response to bacterial infection, promoting plasma
CC membrane repair (PubMed:18667412, PubMed:22464733, PubMed:35705808).
CC Upon inflammasome activation, during DNA virus infection but not RNA
CC virus challenge, controls antiviral immunity through the cleavage of
CC CGAS, rendering it inactive (PubMed:28314590). In apoptotic cells,
CC cleaves SPHK2 which is released from cells and remains enzymatically
CC active extracellularly (By similarity). {ECO:0000250|UniProtKB:P29466,
CC ECO:0000269|PubMed:21147462, ECO:0000269|PubMed:28314590,
CC ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:35705808}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for an Asp residue at position P1 and has a
CC preferred cleavage sequence of Tyr-Val-Ala-Asp-|-.; EC=3.4.22.36;
CC Evidence={ECO:0000269|PubMed:18667412, ECO:0000269|PubMed:21147462,
CC ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:35705808};
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a
CC 10 kDa (Caspase-1 subunit p10) subunit (PubMed:32109412). May be a
CC component of the inflammasome, a protein complex which also includes
CC PYCARD, CARD8 and NLRP2 and whose function would be the activation of
CC pro-inflammatory caspases (By similarity). Component of the AIM2
CC PANoptosome complex, a multiprotein complex that drives inflammatory
CC cell death (PANoptosis) (PubMed:34471287). Both the p10 and p20
CC subunits interact with MEFV (By similarity). Interacts with
CC CARD17P/INCA and CARD18 (By similarity). Interacts with SERPINB1; this
CC interaction regulates CASP1 activity (By similarity).
CC {ECO:0000250|UniProtKB:P29466, ECO:0000269|PubMed:32109412,
CC ECO:0000269|PubMed:34471287}.
CC -!- SUBUNIT: [Caspase-1 subunit p20]: Heterotetramer that consists of two
CC anti-parallel arranged heterodimers, each one formed by a 20 kDa
CC (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit.
CC {ECO:0000269|PubMed:32109412}.
CC -!- SUBUNIT: [Caspase-1 subunit p10]: Heterotetramer that consists of two
CC anti-parallel arranged heterodimers, each one formed by a 20 kDa
CC (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit.
CC {ECO:0000269|PubMed:32109412}.
CC -!- INTERACTION:
CC P29452; Q3UP24: Nlrc4; NbExp=2; IntAct=EBI-489700, EBI-16006652;
CC P29452; Q9EPB4: Pycard; NbExp=2; IntAct=EBI-489700, EBI-6253348;
CC P29452; P18011: sctE; Xeno; NbExp=3; IntAct=EBI-489700, EBI-490239;
CC P29452; Q56134: sctE1; Xeno; NbExp=2; IntAct=EBI-489700, EBI-489689;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21147462}. Cell
CC membrane {ECO:0000250|UniProtKB:P29466}.
CC -!- TISSUE SPECIFICITY: High level expression seen in spleen and lung, low
CC level expression seen in brain, heart, liver, kidney, testis and
CC skeletal muscle. {ECO:0000269|PubMed:1431103}.
CC -!- PTM: The two subunits are derived from the precursor sequence by an
CC autocatalytic mechanism. {ECO:0000269|PubMed:21147462,
CC ECO:0000269|PubMed:32109412}.
CC -!- PTM: Ubiquitinated via 'Lys-11'-linked polyubiquitination.
CC Deubiquitinated by USP8. {ECO:0000250|UniProtKB:P29466}.
CC -!- DISRUPTION PHENOTYPE: Mutants are resitant to vaccinia virus (VACV) but
CC not vesicular somatitis virus (VSV) infection. They show lower viral
CC loads in the lungs compared to wild type mice, they produce higher
CC levels of type I IFN, IL6 and RSAD2/Viperin after VCAV INFECTION.
CC {ECO:0000269|PubMed:28314590}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR EMBL; L03799; AAA39306.1; -; mRNA.
DR EMBL; L28095; AAA20209.1; -; mRNA.
DR EMBL; U04269; AAA56992.1; -; Genomic_DNA.
DR EMBL; BC008152; AAH08152.1; -; mRNA.
DR CCDS; CCDS22798.1; -.
DR PIR; A46495; A46495.
DR RefSeq; NP_033937.2; NM_009807.2.
DR AlphaFoldDB; P29452; -.
DR SMR; P29452; -.
DR BioGRID; 198492; 6.
DR ComplexPortal; CPX-4241; NLRP3 inflammasome.
DR ComplexPortal; CPX-4242; Caspase-1 complex.
DR ComplexPortal; CPX-4243; AIM2 inflammasome.
DR ComplexPortal; CPX-4244; Pyrin inflammasome.
DR ComplexPortal; CPX-4261; NLRP1b inflammasome, allele-1 variant.
DR ComplexPortal; CPX-4266; NLRP1b inflammasome, allele-2 variant.
DR ComplexPortal; CPX-4269; NLRP1b inflammasome, allele-3 variant.
DR ComplexPortal; CPX-4270; NLRP1b inflammasome, allele-5 variant.
DR ComplexPortal; CPX-4271; NLRP1a inflammasome.
DR CORUM; P29452; -.
DR DIP; DIP-34659N; -.
DR IntAct; P29452; 7.
DR MINT; P29452; -.
DR STRING; 10090.ENSMUSP00000027015; -.
DR BindingDB; P29452; -.
DR ChEMBL; CHEMBL4800; -.
DR MEROPS; C14.001; -.
DR iPTMnet; P29452; -.
DR PhosphoSitePlus; P29452; -.
DR SwissPalm; P29452; -.
DR EPD; P29452; -.
DR MaxQB; P29452; -.
DR PaxDb; 10090-ENSMUSP00000027015; -.
DR PeptideAtlas; P29452; -.
DR ProteomicsDB; 279913; -.
DR Antibodypedia; 1075; 1384 antibodies from 47 providers.
DR DNASU; 12362; -.
DR Ensembl; ENSMUST00000027015.7; ENSMUSP00000027015.6; ENSMUSG00000025888.7.
DR GeneID; 12362; -.
DR KEGG; mmu:12362; -.
DR UCSC; uc009obr.1; mouse.
DR AGR; MGI:96544; -.
DR CTD; 834; -.
DR MGI; MGI:96544; Casp1.
DR VEuPathDB; HostDB:ENSMUSG00000025888; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000159114; -.
DR HOGENOM; CLU_036904_0_1_1; -.
DR InParanoid; P29452; -.
DR OMA; CVHKEKD; -.
DR OrthoDB; 2873736at2759; -.
DR PhylomeDB; P29452; -.
DR TreeFam; TF102023; -.
DR BRENDA; 3.4.22.36; 3474.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-448706; Interleukin-1 processing.
DR Reactome; R-MMU-5620971; Pyroptosis.
DR BioGRID-ORCS; 12362; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Casp1; mouse.
DR PRO; PR:P29452; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P29452; Protein.
DR Bgee; ENSMUSG00000025888; Expressed in paneth cell and 116 other cell types or tissues.
DR ExpressionAtlas; P29452; baseline and differential.
DR Genevisible; P29452; MM.
DR GO; GO:0097169; C:AIM2 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0061702; C:canonical inflammasome complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProt.
DR GO; GO:0005829; C:cytosol; IDA:UniProt.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0072557; C:IPAF inflammasome complex; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; NAS:ComplexPortal.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097179; C:protease inhibitor complex; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0050700; F:CARD domain binding; ISO:MGI.
DR GO; GO:0089720; F:caspase binding; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0140970; P:AIM2 inflammasome complex assembly; IDA:UniProt.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:MGI.
DR GO; GO:0071346; P:cellular response to type II interferon; ISO:MGI.
DR GO; GO:0140447; P:cytokine precursor processing; ISO:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IDA:UniProt.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:ARUK-UCL.
DR GO; GO:0051607; P:defense response to virus; NAS:ComplexPortal.
DR GO; GO:0060081; P:membrane hyperpolarization; IMP:MGI.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0001774; P:microglial cell activation; ISO:MGI.
DR GO; GO:0051882; P:mitochondrial depolarization; IMP:MGI.
DR GO; GO:0007520; P:myoblast fusion; ISO:MGI.
DR GO; GO:0007231; P:osmosensory signaling pathway; NAS:ComplexPortal.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; NAS:ComplexPortal.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB.
DR GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:ComplexPortal.
DR GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; IMP:MGI.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; ISO:MGI.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IMP:MGI.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0097300; P:programmed necrotic cell death; IDA:MGI.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0051604; P:protein maturation; IDA:UniProt.
DR GO; GO:0016485; P:protein processing; IDA:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR GO; GO:0070269; P:pyroptosis; IDA:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IMP:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:MGI.
DR GO; GO:0033198; P:response to ATP; IMP:MGI.
DR GO; GO:0009617; P:response to bacterium; IMP:MGI.
DR GO; GO:0001666; P:response to hypoxia; IMP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0140448; P:signaling receptor ligand precursor processing; ISO:MGI.
DR CDD; cd08325; CARD_CASP1-like; 1.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 3.40.50.1460; -; 1.
DR Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR011600; Pept_C14_caspase.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR47901; CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 18; 1.
DR PANTHER; PTHR47901:SF3; CASPASE-1; 1.
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; SSF52129; Caspase-like; 1.
DR SUPFAM; SSF47986; DEATH domain; 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 Apoptosis; Cell membrane; Cytoplasm; Hydrolase; Membrane; Methylation;
KW Phosphoprotein; Protease; Reference proteome; Thiol protease;
KW Ubl conjugation; Zymogen.
FT PROPEP 1..?118
FT /evidence="ECO:0000255"
FT /id="PRO_0000004525"
FT CHAIN ?119..296
FT /note="Caspase-1 subunit p20"
FT /evidence="ECO:0000305|PubMed:32109412"
FT /id="PRO_0000004526"
FT PROPEP 297..314
FT /evidence="ECO:0000255"
FT /id="PRO_0000004527"
FT CHAIN 315..402
FT /note="Caspase-1 subunit p10"
FT /evidence="ECO:0000305|PubMed:32109412"
FT /id="PRO_0000004528"
FT DOMAIN 1..91
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 98..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..122
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 236
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 284
FT /evidence="ECO:0000305|PubMed:21147462"
FT SITE 103..104
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000305|PubMed:21147462"
FT SITE 122..123
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000305|PubMed:21147462"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 343
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MUTAGEN 102..122
FT /note="EDSKGGHPSSSETKEEQNKED->AASKGGHPSSSATKAAQNKAA:
FT Prevents autoprocessing."
FT /evidence="ECO:0000269|PubMed:32109412"
FT MUTAGEN 103
FT /note="D->N: In C71 mutant; abolished cleavage and ability
FT to generate caspase-1 subunits; abolished ability to
FT process inflammatory cytokine interleukin-1 beta (IL1B) and
FT ability to induce programmed cell death; when associated
FT with N-122 and 296-N--N-314."
FT /evidence="ECO:0000269|PubMed:21147462"
FT MUTAGEN 122
FT /note="D->N: In C71 mutant; abolished cleavage and ability
FT to generate caspase-1 subunits; abolished ability to
FT process inflammatory cytokine interleukin-1 beta (IL1B) and
FT ability to induce programmed cell death; when associated
FT with N-103 and 296-N--N-314."
FT /evidence="ECO:0000269|PubMed:21147462"
FT MUTAGEN 284
FT /note="C->A: Loss of protease activity."
FT /evidence="ECO:0000269|PubMed:21147462"
FT MUTAGEN 296..314
FT /note="DSVRDSEEDFLTDAIFEDD->NSVRDSEEDFLTNAIFENN: In C71
FT mutant; abolished cleavage and ability to generate caspase-
FT 1 subunits; abolished ability to process inflammatory
FT cytokine interleukin-1 beta (IL1B) and ability to induce
FT programmed cell death; when associated with N-103 and N-
FT 122."
FT /evidence="ECO:0000269|PubMed:21147462"
FT MUTAGEN 296..314
FT /note="DSVRDSEEDFLTDAIFEDD->NSVRNSEENFLTNAIFENN: In C60
FT mutant; impaired cleavage and ability to generate caspase-1
FT subunits p10 and p20; abolished ability to process
FT inflammatory cytokine interleukin-1 beta (IL1B) without
FT affecting ability to induce programmed cell death."
FT /evidence="ECO:0000269|PubMed:21147462"
FT MUTAGEN 296
FT /note="D->N: In C47 mutant; does not affect ability to
FT mediate inflammatory response; when associated with 313-N-
FT N-314."
FT /evidence="ECO:0000269|PubMed:21147462"
FT MUTAGEN 313..314
FT /note="DD->NN: In C47 mutant; does not affect ability to
FT mediate inflammatory response and cell death; when
FT associated with N-296."
FT /evidence="ECO:0000269|PubMed:21147462"
FT MUTAGEN 316
FT /note="I->N: Mediates autoprocessing but are unable to
FT mediate cleavage of Gasdermin-D (GSDMD)."
FT /evidence="ECO:0000269|PubMed:32109412"
FT CONFLICT 3..6
FT /note="DKIL -> V (in Ref. 3; AAA56992)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 402 AA; 45640 MW; 3BEBCEFA67C69B03 CRC64;
MADKILRAKR KQFINSVSIG TINGLLDELL EKRVLNQEEM DKIKLANITA MDKARDLCDH
VSKKGPQASQ IFITYICNED CYLAGILELQ SAPSAETFVA TEDSKGGHPS SSETKEEQNK
EDGTFPGLTG TLKFCPLEKA QKLWKENPSE IYPIMNTTTR TRLALIICNT EFQHLSPRVG
AQVDLREMKL LLEDLGYTVK VKENLTALEM VKEVKEFAAC PEHKTSDSTF LVFMSHGIQE
GICGTTYSNE VSDILKVDTI FQMMNTLKCP SLKDKPKVII IQACRGEKQG VVLLKDSVRD
SEEDFLTDAI FEDDGIKKAH IEKDFIAFCS STPDNVSWRH PVRGSLFIES LIKHMKEYAW
SCDLEDIFRK VRFSFEQPEF RLQMPTADRV TLTKRFYLFP GH
//
