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}.
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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
//
