ID   CASP1_RAT               Reviewed;         402 AA.
AC   P43527;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   27-MAR-2024, entry version 171.
DE   RecName: Full=Caspase-1;
DE            Short=CASP-1;
DE            EC=3.4.22.36 {ECO:0000250|UniProtKB:P29466};
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:0000250|UniProtKB:P29466};
DE   Contains:
DE     RecName: Full=Caspase-1 subunit p10 {ECO:0000250|UniProtKB:P29466};
DE   Flags: Precursor;
GN   Name=Casp1; Synonyms=Il1bc, Il1bce;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Spleen;
RX   PubMed=7780029; DOI=10.1006/cyto.1995.1014;
RA   Keane K.M., Giegel D.A., Lipinski W.J., Callahan M.J., Shivers B.D.;
RT   "Cloning, tissue expression and regulation of rat interleukin 1 beta
RT   converting enzyme.";
RL   Cytokine 7:105-110(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 228-362.
RC   TISSUE=Ovary;
RX   PubMed=7588240; DOI=10.1210/endo.136.11.7588240;
RA   Flaws J.A., Kugu K., Trbovich A.M., Desanti A., Tilly K.I.,
RA   Hirshfield A.N., Tilly J.L.;
RT   "Interleukin-1 beta-converting enzyme-related proteases (IRPs) and
RT   mammalian cell death: dissociation of IRP-induced oligonucleosomal
RT   endonuclease activity from morphological apoptosis in granulosa cells of
RT   the ovarian follicle.";
RL   Endocrinology 136:5042-5053(1995).
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. Plays a key role in cell immunity
CC       as an inflammatory response initiator: once activated through formation
CC       of an inflammasome complex, it initiates a pro-inflammatory response
CC       through the cleavage of the two inflammatory cytokines IL1B and IL18,
CC       releasing the mature cytokines which are involved in a variety of
CC       inflammatory processes. Cleaves a tetrapeptide after an Asp residue at
CC       position P1. Also initiates pyroptosis, a programmed lytic cell death
CC       pathway, through cleavage of GSDMD. In contrast to cleavage of
CC       interleukin IL1B, recognition and cleavage of GSDMD is not strictly
CC       dependent on the consensus cleavage site but depends on an exosite
CC       interface on CASP1 that recognizes and binds the Gasdermin-D, C-
CC       terminal (GSDMD-CT) part. Cleaves and activates CASP7 in response to
CC       bacterial infection, promoting plasma membrane repair. Upon
CC       inflammasome activation, during DNA virus infection but not RNA virus
CC       challenge, controls antiviral immunity through the cleavage of CGAS,
CC       rendering it inactive. In apoptotic cells, cleaves SPHK2 which is
CC       released from cells and remains enzymatically active extracellularly.
CC       {ECO:0000250|UniProtKB:P29466}.
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:0000250|UniProtKB:P29466};
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. May be a component of the
CC       inflammasome, a protein complex which also includes PYCARD, CARD8 and
CC       NLRP2 and whose function would be the activation of pro-inflammatory
CC       caspases. Component of the AIM2 PANoptosome complex, a multiprotein
CC       complex that drives inflammatory cell death (PANoptosis). Both the p10
CC       and p20 subunits interact with MEFV. Interacts with CARD17P/INCA and
CC       CARD18. Interacts with SERPINB1; this interaction regulates CASP1
CC       activity. {ECO:0000250|UniProtKB:P29452, ECO:0000250|UniProtKB:P29466}.
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:0000250|UniProtKB:P29466}.
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:0000250|UniProtKB:P29466}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P29466}. Cell
CC       membrane {ECO:0000250|UniProtKB:P29466}.
CC   -!- PTM: The two subunits are derived from the precursor sequence by an
CC       autocatalytic mechanism. {ECO:0000250|UniProtKB:P29466}.
CC   -!- PTM: Ubiquitinated via 'Lys-11'-linked polyubiquitination.
CC       Deubiquitinated by USP8. {ECO:0000250|UniProtKB:P29466}.
CC   -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR   EMBL; U14647; AAA85812.1; -; mRNA.
DR   EMBL; U34621; AAC52259.1; -; mRNA.
DR   EMBL; S79676; AAB35431.1; -; mRNA.
DR   AlphaFoldDB; P43527; -.
DR   SMR; P43527; -.
DR   DIP; DIP-29840N; -.
DR   IntAct; P43527; 1.
DR   STRING; 10116.ENSRNOP00000009993; -.
DR   MEROPS; C14.001; -.
DR   PhosphoSitePlus; P43527; -.
DR   PaxDb; 10116-ENSRNOP00000009993; -.
DR   UCSC; RGD:2274; rat.
DR   AGR; RGD:2274; -.
DR   RGD; 2274; Casp1.
DR   eggNOG; KOG3573; Eukaryota.
DR   InParanoid; P43527; -.
DR   PhylomeDB; P43527; -.
DR   BRENDA; 3.4.22.36; 5301.
DR   Reactome; R-RNO-168638; NOD1/2 Signaling Pathway.
DR   Reactome; R-RNO-448706; Interleukin-1 processing.
DR   Reactome; R-RNO-5620971; Pyroptosis.
DR   PRO; PR:P43527; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0097169; C:AIM2 inflammasome complex; ISS:UniProtKB.
DR   GO; GO:0061702; C:canonical inflammasome complex; ISO:RGD.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0005576; C:extracellular region; ISO:RGD.
DR   GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB.
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:RGD.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0050700; F:CARD domain binding; ISO:RGD.
DR   GO; GO:0089720; F:caspase binding; IBA:GO_Central.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0019900; F:kinase binding; ISO:RGD.
DR   GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR   GO; GO:0097110; F:scaffold protein binding; IPI:RGD.
DR   GO; GO:0140970; P:AIM2 inflammasome complex assembly; ISO:RGD.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR   GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR   GO; GO:0071346; P:cellular response to type II interferon; ISO:RGD.
DR   GO; GO:0140447; P:cytokine precursor processing; ISO:RGD.
DR   GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:RGD.
DR   GO; GO:0030324; P:lung development; IEP:RGD.
DR   GO; GO:0060081; P:membrane hyperpolarization; ISO:RGD.
DR   GO; GO:0007613; P:memory; IMP:RGD.
DR   GO; GO:0001774; P:microglial cell activation; IMP:RGD.
DR   GO; GO:0007494; P:midgut development; IEP:RGD.
DR   GO; GO:0051882; P:mitochondrial depolarization; ISO:RGD.
DR   GO; GO:0007520; P:myoblast fusion; IMP:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:RGD.
DR   GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; IMP:RGD.
DR   GO; GO:0001819; P:positive regulation of cytokine production; IMP:RGD.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR   GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; ISO:RGD.
DR   GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:RGD.
DR   GO; GO:0032741; P:positive regulation of interleukin-18 production; ISO:RGD.
DR   GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISO:RGD.
DR   GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; ISO:RGD.
DR   GO; GO:0097300; P:programmed necrotic cell death; ISO:RGD.
DR   GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR   GO; GO:0051604; P:protein maturation; ISO:RGD.
DR   GO; GO:0016485; P:protein processing; ISO:RGD.
DR   GO; GO:0006508; P:proteolysis; ISO:RGD.
DR   GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR   GO; GO:0010506; P:regulation of autophagy; ISO:RGD.
DR   GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR   GO; GO:0033198; P:response to ATP; ISO:RGD.
DR   GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IMP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR   GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR   GO; GO:0140448; P:signaling receptor ligand precursor processing; ISO:RGD.
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   2: Evidence at transcript level;
KW   Apoptosis; Cell membrane; Cytoplasm; Hydrolase; Membrane; Phosphoprotein;
KW   Protease; Reference proteome; Thiol protease; Ubl conjugation; Zymogen.
FT   PROPEP          1..?118
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000004533"
FT   CHAIN           ?119..296
FT                   /note="Caspase-1 subunit p20"
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT                   /id="PRO_0000004534"
FT   PROPEP          297..314
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000004535"
FT   CHAIN           315..402
FT                   /note="Caspase-1 subunit p10"
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT                   /id="PRO_0000004536"
FT   DOMAIN          1..91
FT                   /note="CARD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT   ACT_SITE        236
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT   ACT_SITE        284
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT   MOD_RES         301
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P29452"
FT   CONFLICT        252
FT                   /note="A -> G (in Ref. 2; AAC52259/AAB35431)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        256
FT                   /note="K -> E (in Ref. 2; AAC52259/AAB35431)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        260
FT                   /note="I -> L (in Ref. 2; AAC52259/AAB35431)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        262
FT                   /note="Q -> H (in Ref. 2; AAC52259/AAB35431)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        343
FT                   /note="R -> Q (in Ref. 2; AAC52259/AAB35431)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   402 AA;  45576 MW;  D2E8FA2BEA76FD40 CRC64;
     MADKVLRAKR KQFINSVSVG TINGLLDELL EKRVLNQEEM DTIKLANITV MEKARDLCDH
     VTKKGPRASQ MFITYICNED CYLAEILELQ SGPSAETVFV TEDSKGGHPF SSETKEKLNK
     EGGAFPGPSG SLKFCPLEIA QKLWKENHSE IYPIMKTPTR TRLALIICNT DFQHLSRRVG
     ADVDLREMKL LLQDLGYTVK VKENLTALEM TKELKEFAAC PEHKTSDSTF LVFMSHGLQE
     GICGITYSNE VADILKVDTI FQMMNTLKCP SLKDKPKVII IQACRGEKQG VVLLKDSVGN
     SEEGFLTDAI FEDDGIKKAH IEKDFIAFCS STPDNVSWRH PVRGSLFIES LIKHMKEYAW
     SCDLEDIFRK VRFSFEQPDS RLQMPTTERV TLTKRFYLFP GH
//