CASPA_DANRE
ID CASPA_DANRE Reviewed; 383 AA.
AC Q9I9L7; A0A2U9DQN4;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Caspase a {ECO:0000312|ZFIN:ZDB-GENE-000616-3};
DE EC=3.4.22.36 {ECO:0000269|PubMed:12464617};
DE Contains:
DE RecName: Full=Caspase a subunit p20 {ECO:0000305|PubMed:30150286};
DE Contains:
DE RecName: Full=Caspase a subunit p10 {ECO:0000305|PubMed:30150286};
DE Flags: Precursor;
GN Name=caspa {ECO:0000312|ZFIN:ZDB-GENE-000616-3};
GN Synonyms=casp1 {ECO:0000312|ZFIN:ZDB-GENE-000616-3},
GN caspy {ECO:0000312|ZFIN:ZDB-GENE-000616-3};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AAF66964.1};
RN [1] {ECO:0000312|EMBL:AWP39886.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=29791492; DOI=10.1371/journal.pone.0197966;
RA Spead O., Verreet T., Donelson C.J., Poulain F.E.;
RT "Characterization of the caspase family in zebrafish.";
RL PLoS ONE 13:E0197966-E0197966(2018).
RN [2] {ECO:0000312|EMBL:AAF66964.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10917738; DOI=10.1038/sj.cdd.4400679;
RA Inohara N., Nunez G.;
RT "Genes with homology to mammalian apoptosis regulators identified in
RT zebrafish.";
RL Cell Death Differ. 7:509-510(2000).
RN [3] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [4] {ECO:0000312|EMBL:AAH95022.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Larva {ECO:0000312|EMBL:AAH95022.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PYCARD, SUBCELLULAR
RP LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=12464617; DOI=10.1074/jbc.m203944200;
RA Masumoto J., Zhou W., Chen F.F., Su F., Kuwada J.Y., Hidaka E.,
RA Katsuyama T., Sagara J., Taniguchi S., Ngo-Hazelett P., Postlethwait J.H.,
RA Nunez G., Inohara N.;
RT "Caspy, a zebrafish caspase, activated by ASC oligomerization is required
RT for pharyngeal arch development.";
RL J. Biol. Chem. 278:4268-4276(2003).
RN [6] {ECO:0000305}
RP DEVELOPMENTAL STAGE, AND INDUCTION BY PENTACHLOROPHENOL.
RX PubMed=28402832; DOI=10.1016/j.chemosphere.2017.03.100;
RA Zhao J., Huang G., Xu T., Yin D., Bai J., Gu W.;
RT "Early developmental exposure to pentachlorophenol causes alterations on
RT mRNA expressions of caspase protease family in zebrafish embryos.";
RL Chemosphere 180:141-148(2017).
RN [7] {ECO:0000305}
RP INTERACTION WITH CAIAP.
RX PubMed=29123523; DOI=10.3389/fimmu.2017.01375;
RA Tyrkalska S.D., Candel S., Perez-Oliva A.B., Valera A., Alcaraz-Perez F.,
RA Garcia-Moreno D., Cayuela M.L., Mulero V.;
RT "Identification of an Evolutionarily Conserved Ankyrin Domain-Containing
RT Protein, Caiap, Which Regulates Inflammasome-Dependent Resistance to
RT Bacterial Infection.";
RL Front. Immunol. 8:1375-1375(2017).
RN [8] {ECO:0000305}
RP INTERACTION WITH PYCARD AND CASPB.
RX PubMed=29791979; DOI=10.1111/febs.14514;
RA Li Y., Huang Y., Cao X., Yin X., Jin X., Liu S., Jiang J., Jiang W.,
RA Xiao T.S., Zhou R., Cai G., Hu B., Jin T.;
RT "Functional and structural characterization of zebrafish ASC.";
RL FEBS J. 285:2691-2707(2018).
RN [9] {ECO:0000305}
RP FUNCTION, PROTEOLYTIC CLEAVAGE, IDENTIFICATION IN NLRP1 INFLAMMASOME,
RP INTERACTION WITH PYCARD, SUBCELLULAR LOCATION, INDUCTION BY E.TARDA, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=30150286; DOI=10.4049/jimmunol.1800498;
RA Li J.Y., Gao K., Shao T., Fan D.D., Hu C.B., Sun C.C., Dong W.R., Lin A.F.,
RA Xiang L.X., Shao J.Z.;
RT "Characterization of an NLRP1 Inflammasome from Zebrafish Reveals a Unique
RT Sequential Activation Mechanism Underlying Inflammatory Caspases in Ancient
RT Vertebrates.";
RL J. Immunol. 201:1946-1966(2018).
CC -!- FUNCTION: Thiol protease which cleaves IL-1 beta (il1b), releasing the
CC mature cytokine which is involved in a variety of inflammatory
CC processes, and mediates apoptosis (PubMed:12464617, PubMed:30150286).
CC Component of the NLRP1 inflammasome, which plays a crucial role in
CC innate immunity and inflammation (PubMed:30150286). In response to
CC pathogens and other damage-associated signals, recruited to the NLRP1
CC inflammasome in its precursor form (PubMed:30150286). Its subsequent
CC activation causes the cleavage of pro-il1b into the midformed il1b,
CC which then evetually leads to il1b maturation and secretion in the
CC extracellular milieu (PubMed:30150286). Required for the development of
CC the cartilaginous pharyngeal skeleton (PubMed:12464617).
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30150286}.
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:0000269|PubMed:12464617};
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 20 kDa (p20) and a 10 kDa (p10)
CC subunit (Probable). Interacts (via pyrin domain) with pycard (via pyrin
CC domain) (PubMed:12464617, PubMed:29791979, PubMed:30150286). Interacts
CC with caspb (PubMed:29791979). Component of NLRP1 inflammasomes
CC (PubMed:30150286). Inflammasomes are supramolecular complexes that
CC assemble in the cytosol in response to pathogens and other damage-
CC associated signals and play critical roles in innate immunity and
CC inflammation (PubMed:30150286). The NLRP1 inflammasome is composed of
CC the signal sensor nlrp1, and the adapter pycard (asc), which recruit
CC effector pro-inflammatory caspases caspa and/or caspb
CC (PubMed:30150286). The interaction between nlrp1 and pycard is required
CC for the sequential recruitment of caspa and then caspb
CC (PubMed:30150286). Caspa is preferentially recruited first and this
CC causes the cleavage of pro-il1b into the midformed il1b
CC (PubMed:30150286). This is followed by the recruitment of caspb, which
CC is activated and cleaves the midformed il1b resulting in il1b
CC maturation (PubMed:30150286). Interacts with caiap (PubMed:29123523).
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:29123523,
CC ECO:0000269|PubMed:29791979, ECO:0000269|PubMed:30150286,
CC ECO:0000305|PubMed:30150286}.
CC -!- SUBCELLULAR LOCATION: Inflammasome {ECO:0000269|PubMed:30150286}.
CC Cytoplasm {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30150286}.
CC Note=Co-localizes with pycard, nlrp1 and caspb in the cytoplasm
CC (PubMed:30150286). Co-localizes with pycard at large cytoplasmic
CC aggregates, known as specks (PubMed:12464617, PubMed:30150286).
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30150286}.
CC -!- DEVELOPMENTAL STAGE: During embryonic development, highly expressed at
CC 8 hours post-fertilization (hpf) (PubMed:28402832). Expressed at the
CC pharyngula stage at 24 hpf and expression is maintained 48 hpf, 72 hpf
CC and to larval day 4 of development at 96 hpf (PubMed:29791492,
CC PubMed:28402832). During this time, expressed in the pharyngeal arches,
CC and in the intestinal bulb at 72 and 96 hpf (PubMed:29791492,
CC PubMed:12464617). Also expressed in the epidermis and mouth at 48 and
CC 72 hpf (PubMed:12464617). {ECO:0000269|PubMed:12464617,
CC ECO:0000269|PubMed:28402832, ECO:0000269|PubMed:29791492}.
CC -!- INDUCTION: Up-regulated in response to pentachlorophenol (PCP), a toxic
CC pollutant (PubMed:28402832). Up-regulated in response to bacterial
CC infection with E.tarda (PubMed:30150286). {ECO:0000269|PubMed:28402832,
CC ECO:0000269|PubMed:30150286}.
CC -!- PTM: The two subunits are derived from the precursor sequence by an
CC autocatalytic mechanism. {ECO:0000305|PubMed:30150286}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown in early embryos results in
CC abnormalities in the development of the cartilaginous pharyngeal
CC skeleton and eventually results in death upon exhaustion of the yolk
CC (PubMed:12464617). Abnormalities include deformed and thinned Meckel's
CC and palatoquadrate cartilages, deformed ceratohyal cartilages and
CC disorganized branchial cartilages (PubMed:12464617). Morpholino
CC knockdown in one- to four-cell stage embryos results in an open mouth
CC phenotype (PubMed:12464617). Morpholino knockdown in one-cell embryos
CC results in reduced survival in response to bacterial infection with
CC E.tarda, but does not decrease caspb activation (PubMed:30150286).
CC Morpholino knockdown in larvae results in no abnormalities in the
CC brain, eyes or pectoral fins (PubMed:12464617).
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30150286}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU003971}.
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DR EMBL; MG957992; AWP39886.1; -; mRNA.
DR EMBL; AF233434; AAF66964.1; -; mRNA.
DR EMBL; BX649388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC095022; AAH95022.1; -; mRNA.
DR EMBL; BC164780; AAI64780.1; -; mRNA.
DR RefSeq; NP_571580.1; NM_131505.2.
DR AlphaFoldDB; Q9I9L7; -.
DR SMR; Q9I9L7; -.
DR ComplexPortal; CPX-4947; NLRP1 inflammasome, variant 1.
DR ComplexPortal; CPX-4948; NLRP1 inflammasome, variant 2.
DR IntAct; Q9I9L7; 1.
DR STRING; 7955.ENSDARP00000034228; -.
DR MEROPS; C14.030; -.
DR PaxDb; Q9I9L7; -.
DR Ensembl; ENSDART00000034544; ENSDARP00000034228; ENSDARG00000008165.
DR GeneID; 57933; -.
DR KEGG; dre:57933; -.
DR CTD; 57933; -.
DR ZFIN; ZDB-GENE-000616-3; caspa.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000162428; -.
DR HOGENOM; CLU_036904_0_1_1; -.
DR InParanoid; Q9I9L7; -.
DR OrthoDB; 1327703at2759; -.
DR PhylomeDB; Q9I9L7; -.
DR TreeFam; TF102023; -.
DR Reactome; R-DRE-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-DRE-448706; Interleukin-1 processing.
DR Reactome; R-DRE-9008059; Interleukin-37 signaling.
DR PRO; PR:Q9I9L7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 16.
DR Bgee; ENSDARG00000008165; Expressed in granulocyte and 16 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:ComplexPortal.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:ZFIN.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0032090; F:Pyrin domain binding; IPI:ZFIN.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IMP:ZFIN.
DR GO; GO:0045087; P:innate immune response; IGI:ZFIN.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ZFIN.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IC:ComplexPortal.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR004020; DAPIN.
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; PF02758; PYRIN; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 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.
DR PROSITE; PS50824; DAPIN; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Inflammasome; Protease; Reference proteome;
KW Thiol protease; Zymogen.
FT PROPEP 1..142
FT /evidence="ECO:0000305"
FT /id="PRO_0000448780"
FT CHAIN 143..274
FT /note="Caspase a subunit p20"
FT /id="PRO_0000448781"
FT PROPEP 275..296
FT /evidence="ECO:0000305"
FT /id="PRO_0000448782"
FT CHAIN 297..383
FT /note="Caspase a subunit p10"
FT /id="PRO_0000448783"
FT DOMAIN 8..81
FT /note="Pyrin"
FT /evidence="ECO:0000255"
FT REGION 87..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 220
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 270
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT CONFLICT 51
FT /note="L -> V (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 65
FT /note="S -> F (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="V -> I (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="T -> I (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="S -> A (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 177
FT /note="K -> M (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="R -> H (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="I -> M (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
FT CONFLICT 354..355
FT /note="EH -> DN (in Ref. 1; AWP39886)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 383 AA; 43966 MW; 21890871309774C3 CRC64;
MAKSIKDHLQ DALSNIGADN LRRFQSRLGD RKQEPRVRKS TIEKLKDEID LVDLLVNTFT
SDAVSVTVDI LRGIKCNAVA EELLENTGQG GVSQPEPPVP EPIPKDPAQL KELKVTPCSQ
QFKNKILREK GQETYEIKDK SVRKRLALLI NNVDFDDKAM KRSGSEKDEE NMEKLLKELD
YQVVKRPNLS AKEMDEAIRD FAQREEHKYS DSAFVVIMSH GKRDAIMGVH YHRTNNPSDS
FPVDNVYRRL NSENCPALRD KPKVILIQAC RGGEHGRVWA SDGEPDEPIE IEDDDFVHKE
KDFISLMSCT PDTKSYRHVQ NGTFYVQTLV DVFIKCAHED HIEELFRKVL RRFEHPNMIG
NFKQMACKDR ATLPKLFYLF PGL
