CASP1_RAT
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 03-AUG-2022, entry version 162.
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 interleukins IL1B and IL1B, recognition and cleavage of GSDMD is not
CC strictly dependent on the consensus cleavage site but depends on an
CC exosite interface on CASP1 that recognizes and binds the Gasdermin-D,
CC C-terminal (GSDMD-CT) part. Upon inflammasome activation, during DNA
CC virus infection but not RNA virus challenge, controls antiviral
CC immunity through the cleavage of CGAS, rendering it inactive. In
CC apoptotic cells, cleaves SPHK2 which is released from cells and remains
CC enzymatically active extracellularly. {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 CARD17/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}.
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; 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; P43527; -.
DR UCSC; RGD:2274; rat.
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:0008303; C:caspase complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0061702; C:inflammasome complex; ISO:RGD.
DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
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:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
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:0006915; P:apoptotic process; IEP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:RGD.
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:0140447; P:cytokine precursor processing; 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:0002221; P:pattern recognition receptor signaling pathway; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; IMP:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO: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:0043525; P:positive regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; 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: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 GO; GO:1901998; P:toxin transport; ISO:RGD.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 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; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR Pfam; PF00619; CARD; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 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
