ID   CAS1A_XENLA             Reviewed;         386 AA.
AC   P55865; A2VD67;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   03-AUG-2022, entry version 113.
DE   RecName: Full=Caspase-1-A;
DE            Short=CASP-1-A;
DE            EC=3.4.22.36 {ECO:0000250|UniProtKB:P29466};
DE   AltName: Full=Interleukin-1 beta convertase homolog A;
DE            Short=xICE-A;
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-a; Synonyms=casp1a;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9030578; DOI=10.1074/jbc.272.8.5122;
RA   Yaoita Y., Nakajima K.;
RT   "Induction of apoptosis and CPP32 expression by thyroid hormone in a
RT   myoblastic cell line derived from tadpole tail.";
RL   J. Biol. Chem. 272:5122-5127(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Spleen;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
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. {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. {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       Can form a heterodimer with isoform epsilon which then has an
CC       inhibitory effect. {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   -!- 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; D89783; BAA14017.1; -; mRNA.
DR   EMBL; BC129548; AAI29549.1; -; mRNA.
DR   RefSeq; NP_001081223.1; NM_001087754.1.
DR   AlphaFoldDB; P55865; -.
DR   SMR; P55865; -.
DR   DNASU; 397719; -.
DR   GeneID; 397719; -.
DR   KEGG; xla:397719; -.
DR   CTD; 397719; -.
DR   Xenbase; XB-GENE-6252623; casp1.L.
DR   OMA; WKMKMDD; -.
DR   OrthoDB; 1327703at2759; -.
DR   Proteomes; UP000186698; Chromosome 2L.
DR   Bgee; 397719; Expressed in spleen and 20 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
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   Cell membrane; Cytoplasm; Hydrolase; Membrane; Protease;
KW   Reference proteome; Thiol protease; Zymogen.
FT   PROPEP          1..100
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000004537"
FT   CHAIN           101..286
FT                   /note="Caspase-1 subunit p20"
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT                   /id="PRO_0000451686"
FT   PROPEP          287..296
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT                   /id="PRO_0000451687"
FT   CHAIN           297..386
FT                   /note="Caspase-1 subunit p10"
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT                   /id="PRO_0000451688"
FT   DOMAIN          22..88
FT                   /note="CARD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT   ACT_SITE        218
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
FT   ACT_SITE        274
FT                   /evidence="ECO:0000250|UniProtKB:P29466"
SQ   SEQUENCE   386 AA;  43663 MW;  927C71FC9FED79E6 CRC64;
     MTAQLNKVRR AIIDGCNPAM ISDLLDDLRE KNVLVDSEVE HIKESNNTNR DRCRAMIDSV
     KKKGDDPSNI LLESLVKNHK TLAKSLGLHE PPMAPVPIQE HNADTIKNKD IKGVIPCSAE
     EFKKIQDTQG DKIYDVRKRE GRKGLALIIC NEKFENLNER HGAKVDLDGM TKLLNELGYQ
     VHPHTNLTKT EMVKVMKEFA AQEEHADSDS TFIVLMSHGD RQGVCGTDSK KTEKEKGQYE
     VTNLLEIDEI FSTFNNVNCS KLRNKPKVII IQACRGENKG GLLVRDDVAS PPLEDDGLHF
     VQREADFICF CSSTPDTVSW RDPTKGSVFI THLIEKMNEY AHCQPLGDIF LEVQSLFKDK
     CPNSRSQMPT QERCTLTKKF YLFPGY