ID   CASP1_HORSE             Reviewed;         405 AA.
AC   Q9TV13;
DT   05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 143.
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   Equus caballus (Horse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX   NCBI_TaxID=9796;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10376217; DOI=10.3109/10425179909008431;
RA   Wardlow S., Penha-Goncalves M.N., Argyle D.J., Onions D.E., Nicolson L.;
RT   "Nucleotide sequence of equine caspase-1 cDNA.";
RL   DNA Seq. 10:133-137(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       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}.
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; AF090119; AAD46400.1; -; mRNA.
DR   RefSeq; NP_001075311.1; NM_001081842.1.
DR   AlphaFoldDB; Q9TV13; -.
DR   SMR; Q9TV13; -.
DR   STRING; 9796.ENSECAP00000021890; -.
DR   PaxDb; 9796-ENSECAP00000021890; -.
DR   GeneID; 100033888; -.
DR   KEGG; ecb:100033888; -.
DR   CTD; 834; -.
DR   InParanoid; Q9TV13; -.
DR   OrthoDB; 2873736at2759; -.
DR   BRENDA; 3.4.22.36; 2120.
DR   Proteomes; UP000002281; Unplaced.
DR   GO; GO:0097169; C:AIM2 inflammasome complex; ISS:UniProtKB.
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:0089720; F:caspase binding; IBA:GO_Central.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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; 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..119
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000004517"
FT   CHAIN           120..298
FT                   /note="Caspase-1 subunit p20"
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT                   /id="PRO_0000004518"
FT   PROPEP          299..317
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000004519"
FT   CHAIN           318..405
FT                   /note="Caspase-1 subunit p10"
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT                   /id="PRO_0000004520"
FT   DOMAIN          1..91
FT                   /note="CARD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT   ACT_SITE        238
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT   ACT_SITE        286
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT   MOD_RES         303
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P29452"
FT   VARIANT         203
FT                   /note="V -> L"
FT   VARIANT         305
FT                   /note="N -> S"
SQ   SEQUENCE   405 AA;  45331 MW;  7CE8729BB359CC17 CRC64;
     MADKVLKEKR RLFIRSVGTG TVNSLLDELL EKRVLNQEEM EKVRDENATV MDKARALIDA
     VIRKGPQACQ IFIGHICEDD PHLAETLRLS SGPQSGNFLK TQDSQAVVHS SPALQAMPDD
     LAKLALSGPK VSLKLCSPEV VERIWKEKSA EMYPIMGKSM TRTRLALIIC NTEFDNLSRR
     AGAEVDIASM KVLLEGLGYS VEVKENLTAL DMTTELKAFA ARPEHRSSDS TFLVFMSHGI
     REGICGKKFS EKVPDVLEVN TIFQIFNTRN CPNLRDKPKV IIIQACRGEN QGVVWLKDST
     GTSGNSSSLA PDDFEDDAIK KAHVEKDFIA FCSSTPDTVS WRSPTTGSVF IEKLIENLQE
     YAWSCDLEEI FRKVRLSFEL PDARAQMPTA ERVTLTRRFY LFPGH
//