CSP1_CAEEL
ID CSP1_CAEEL Reviewed; 536 AA.
AC G5EBM1; G5EBN4; G5EG94;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Caspase A {ECO:0000305};
DE EC=3.4.22.36 {ECO:0000269|PubMed:9857046};
DE Contains:
DE RecName: Full=Caspase A subunit p16 {ECO:0000305|PubMed:9857046};
DE Contains:
DE RecName: Full=Caspase A subunit p14 {ECO:0000305|PubMed:9857046};
DE Flags: Precursor;
GN Name=csp-1 {ECO:0000303|PubMed:9857046, ECO:0000312|WormBase:Y48E1B.13a};
GN ORFNames=Y48E1B.13 {ECO:0000312|WormBase:Y48E1B.13a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAC98292.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), PARTIAL PROTEIN SEQUENCE,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, PROTEOLYTIC
RP CLEAVAGE, ACTIVE SITE, AND MUTAGENESIS OF CYS-406.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC98292.1};
RX PubMed=9857046; DOI=10.1074/jbc.273.52.35109;
RA Shaham S.;
RT "Identification of multiple Caenorhabditis elegans caspases and their
RT potential roles in proteolytic cascades.";
RL J. Biol. Chem. 273:35109-35117(1998).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23721876; DOI=10.1016/j.neuro.2013.05.014;
RA Settivari R., VanDuyn N., LeVora J., Nass R.;
RT "The Nrf2/SKN-1-dependent glutathione S-transferase pi homologue GST-1
RT inhibits dopamine neuron degeneration in a Caenorhabditis elegans model of
RT manganism.";
RL NeuroToxicology 38:51-60(2013).
RN [4] {ECO:0000305}
RP FUNCTION (ISOFORMS A; B AND C), AND DISRUPTION PHENOTYPE.
RX PubMed=23505386; DOI=10.1371/journal.pgen.1003341;
RA Denning D.P., Hatch V., Horvitz H.R.;
RT "Both the caspase CSP-1 and a caspase-independent pathway promote
RT programmed cell death in parallel to the canonical pathway for apoptosis in
RT Caenorhabditis elegans.";
RL PLoS Genet. 9:E1003341-E1003341(2013).
CC -!- FUNCTION: Cysteine protease which, in vitro, cleaves itself and caspase
CC ced-3 into their mature active forms (PubMed:9857046). Also cleaves, in
CC vitro, inactive caspase csp-2 isoform b (PubMed:9857046). Required
CC maternally to induce apoptosis in a subset of cells fated to die during
CC embryogenesis, mostly independently of the ced-9, ced-4 and ced-3
CC canonical apoptosis pathway (PubMed:23505386). Involved in the
CC degeneration of dopaminergic CEP neurons in response to high Mn(2+)
CC levels (PubMed:23721876). {ECO:0000269|PubMed:23505386,
CC ECO:0000269|PubMed:23721876, ECO:0000269|PubMed:9857046}.
CC -!- FUNCTION: [Isoform a]: Dispensable for regulating apoptosis during
CC embryogenesis. {ECO:0000269|PubMed:23505386}.
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:9857046};
CC -!- ACTIVITY REGULATION: Inhibited by cysteine protease inhibitor
CC iodoacetic acid (CH3COOI) but not by N-[N-(L-3-transcarboxirane-2-
CC carbonyl)-leucyl]-agmatine (E-64) or benzyloxycarbonyl-DEVD-fluoro-
CC methyl ketone (Z-DEVD-FMK). {ECO:0000269|PubMed:9857046}.
CC -!- SUBUNIT: Heterodimer formed by the tight association of the large
CC subunit p16 and the small subunit p14. {ECO:0000303|PubMed:9857046}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:Y48E1B.13a};
CC IsoId=G5EBM1-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:Y48E1B.13b};
CC IsoId=G5EBM1-2; Sequence=VSP_058804;
CC Name=c {ECO:0000312|WormBase:Y48E1B.13c};
CC IsoId=G5EBM1-3; Sequence=VSP_058804, VSP_058805, VSP_058806;
CC -!- TISSUE SPECIFICITY: Isoform a: Expression is restricted to the late
CC germline pachytene stage of meiosis I in both L4 larvae and adult
CC hermaphrodite gonads. Isoform b: Expression is restricted to the late
CC germline pachytene stage of meiosis I in both L4 larvae and adult
CC hermaphrodite gonads. {ECO:0000269|PubMed:23505386}.
CC -!- PTM: Autocatalytic cleavage removes the propeptide and generates the
CC two active subunits p16 and p14 in vitro. Cannot be cleaved by ced-3 in
CC vitro. {ECO:0000269|PubMed:9857046}.
CC -!- DISRUPTION PHENOTYPE: Survival of touch neurons and several pharyngeal
CC cells is not affected during development and no extra pharyngeal cells
CC caused by impaired apoptosis are produced (PubMed:23505386). Basal and
CC ionizing radiation-induced germline apoptosis are normal
CC (PubMed:23505386). In a ced-3 n2427 mutant background, more animals
CC have the M4 sister cell that survives (PubMed:23505386). In a csp-3
CC n4872, csp-2 n4871 and ced-3 n3692 mutant background where the
CC canonical apoptotic pathway is impaired, 16 percent of animals have
CC still 1 or more cell corpses that are morphologically apoptotic and are
CC internalized by engulfing cells (PubMed:23505386). In addition,
CC apoptosis of the male linker cell occurs normally (PubMed:23505386).
CC RNAi-mediated knockdown causes a 50 percent inhibition of Mn(2+)-
CC induced dopaminergic CEP neuron degeneration (PubMed:23721876).
CC {ECO:0000269|PubMed:23505386, ECO:0000269|PubMed:23721876}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU003971}.
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DR EMBL; AF088285; AAC98292.1; -; mRNA.
DR EMBL; AF088286; AAC98293.1; -; mRNA.
DR EMBL; AF088287; AAC98294.1; -; mRNA.
DR EMBL; BX284602; CAB07698.2; -; Genomic_DNA.
DR EMBL; BX284602; CAD18879.1; -; Genomic_DNA.
DR EMBL; BX284602; CAD18880.1; -; Genomic_DNA.
DR PIR; T27021; T27021.
DR PIR; T43633; T43633.
DR PIR; T43637; T43637.
DR RefSeq; NP_001022452.1; NM_001027281.1. [G5EBM1-1]
DR RefSeq; NP_001022453.1; NM_001027282.1. [G5EBM1-2]
DR RefSeq; NP_001022454.1; NM_001027283.1. [G5EBM1-3]
DR AlphaFoldDB; G5EBM1; -.
DR SMR; G5EBM1; -.
DR STRING; 6239.Y48E1B.13a; -.
DR MEROPS; C14.A06; -.
DR EPD; G5EBM1; -.
DR PaxDb; G5EBM1; -.
DR EnsemblMetazoa; Y48E1B.13a.1; Y48E1B.13a.1; WBGene00000819. [G5EBM1-1]
DR EnsemblMetazoa; Y48E1B.13b.1; Y48E1B.13b.1; WBGene00000819. [G5EBM1-2]
DR EnsemblMetazoa; Y48E1B.13c.1; Y48E1B.13c.1; WBGene00000819. [G5EBM1-3]
DR GeneID; 175007; -.
DR KEGG; cel:CELE_Y48E1B.13; -.
DR CTD; 175007; -.
DR WormBase; Y48E1B.13a; CE29378; WBGene00000819; csp-1. [G5EBM1-1]
DR WormBase; Y48E1B.13b; CE30016; WBGene00000819; csp-1. [G5EBM1-2]
DR WormBase; Y48E1B.13c; CE30017; WBGene00000819; csp-1. [G5EBM1-3]
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000169659; -.
DR HOGENOM; CLU_508301_0_0_1; -.
DR InParanoid; G5EBM1; -.
DR OrthoDB; 984395at2759; -.
DR PhylomeDB; G5EBM1; -.
DR Reactome; R-CEL-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-CEL-352238; Breakdown of the nuclear lamina.
DR PRO; PR:G5EBM1; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00000819; Expressed in reproductive system and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043073; C:germ cell nucleus; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IBA:GO_Central.
DR GO; GO:0097194; P:execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:1905803; P:negative regulation of cellular response to manganese ion; IMP:UniProtKB.
DR GO; GO:1904747; P:positive regulation of apoptotic process involved in development; IMP:UniProtKB.
DR GO; GO:1905845; P:positive regulation of cellular response to gamma radiation; IGI:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00032; CASc; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR InterPro; IPR006570; SPK_dom.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR Pfam; PF04435; SPK; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SMART; SM00583; SPK; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS01121; CASPASE_HIS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Direct protein sequencing; Hydrolase;
KW Protease; Reference proteome; Thiol protease; Zymogen.
FT PROPEP 1..273
FT /note="Removed in mature form by autoprocessing"
FT /evidence="ECO:0000269|PubMed:9857046"
FT /id="PRO_0000439218"
FT CHAIN 274..418
FT /note="Caspase A subunit p16"
FT /evidence="ECO:0000303|PubMed:9857046"
FT /id="PRO_0000439219"
FT CHAIN 419..536
FT /note="Caspase A subunit p14"
FT /evidence="ECO:0000303|PubMed:9857046"
FT /id="PRO_0000439220"
FT ACT_SITE 364
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 406
FT /evidence="ECO:0000269|PubMed:9857046"
FT VAR_SEQ 1..268
FT /note="Missing (in isoform b and isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_058804"
FT VAR_SEQ 411..417
FT /note="LNMGVPV -> IEHGCSR (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_058805"
FT VAR_SEQ 418..536
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_058806"
FT MUTAGEN 406
FT /note="C->S: Loss of catalytic activity. Loss of
FT autoprocessing."
FT /evidence="ECO:0000269|PubMed:9857046"
SQ SEQUENCE 536 AA; 61467 MW; 089F72490C6AA69E CRC64;
MVLKTIEDNC KSQFDDDLVE DFNNFQTTSS MSSSTTISTE DFNTIEIEST FEICRSGSYT
EEPILGENDE FLIDFEMERF LKFLKDKTKQ VEKRKEPFSQ KEIYAVFQRR IKSELCIETV
KKKFQPLLPN AIQTCEFDEE TMIRMIYGAG IRIDSVDFWN RFTSKATISL DCYSRLISYS
SDSLTLSGTH RSGFTYHWIS TPPVTYHRTE NKDPNIQEPS PVEFLDVQSS LGSSMKPPIL
DKPTKLDDPA ETRHDCSYSL EEYDSQSRMP RTDAKKSNHK HKYCYEMNSN PRGTVLILSN
ENFKNMERRV GTKQDEVNLT KLFQKLQYTV ICKRNLEAES MLEAIKEFAE MAHTDSIILF
LLSHGDGAGS VFGIDDMPVN VMEVSTYLAY HQNLLLKPKW VAVSACRGGK LNMGVPVDGL
PALEDKCAPI SKFWNLMMSR IMPGTFTSLN ADVIISFSTT DGFTSYRDEE AGTWYIKSMC
KVFNKHSKTM HLLDILTETG RNVVTKYENV QGNVVLKQAP EILSRLTKQW HFSRSM
