CASP1_PIG
ID CASP1_PIG Reviewed; 404 AA.
AC Q9N2I1;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 123.
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;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10574622; DOI=10.1089/107999099312966;
RA Muneta Y., Shimoji Y., Yokomizo Y., Mori Y.;
RT "Molecular cloning of porcine interleukin-1beta converting enzyme and
RT differential gene expression of IL-1beta converting enzyme, IL-1beta, and
RT IL-18 in porcine alveolar macrophages.";
RL J. Interferon Cytokine Res. 19:1289-1296(1999).
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}.
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DR EMBL; AB027296; BAA89531.1; -; mRNA.
DR RefSeq; NP_999327.1; NM_214162.1.
DR AlphaFoldDB; Q9N2I1; -.
DR SMR; Q9N2I1; -.
DR STRING; 9823.ENSSSCP00000023919; -.
DR PaxDb; Q9N2I1; -.
DR PeptideAtlas; Q9N2I1; -.
DR GeneID; 397319; -.
DR KEGG; ssc:397319; -.
DR CTD; 834; -.
DR eggNOG; KOG3573; Eukaryota.
DR InParanoid; Q9N2I1; -.
DR OrthoDB; 1327703at2759; -.
DR BRENDA; 3.4.22.36; 6170.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0097169; C:AIM2 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072557; C:IPAF inflammasome complex; ISS:UniProtKB.
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: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:0001819; P:positive regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0070269; P:pyroptosis; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
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..119
FT /evidence="ECO:0000255"
FT /id="PRO_0000004529"
FT CHAIN 120..297
FT /note="Caspase-1 subunit p20"
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT /id="PRO_0000004530"
FT PROPEP 298..316
FT /evidence="ECO:0000255"
FT /id="PRO_0000004531"
FT CHAIN 317..404
FT /note="Caspase-1 subunit p10"
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT /id="PRO_0000004532"
FT DOMAIN 1..91
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 111..132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 237
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 285
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29452"
SQ SEQUENCE 404 AA; 44882 MW; 437DC787E85FB449 CRC64;
MADKVLKEKR RLFVRSVAMG TINGLLDELL ETRVLNQEEV EIVRGENATV MDKARALIDS
VIRKGPQACQ ICINHICGDD PHLAGVLELS TGSQSGKCLT VQESQAVVPP FPAPQTVQDN
PVKPASSEPR GSLKLCPPDI AQRLWKEKSA EIYPIMGKSI RTRLALIICN TEFENLPRRD
GADVDIRDMK ILLEDLGYSV DVRENLTASD MAIELKAFAA RPEHKSSDST FLVLMSHGIQ
AGICGKKYSE EVPDVLEVNT VFQILNTLNC PSLKDKPKVI IIQACRGEKQ GVVWIKDSVG
PSGNSSLLAA EDFEYDAIKK AHIEKDFIAF CSSTPDNVSW RHPLLGSLFI IKLIKILQEH
AWSCGLEEIF RKVRFSFELA DGRAQMPTAE RVTLTRSFYL FPGH
