CSP2_CAEEL
ID CSP2_CAEEL Reviewed; 263 AA.
AC Q9TZP5; A0A1N7SZF9; G5ECY5;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Putative inactive caspase B {ECO:0000305};
DE Contains:
DE RecName: Full=Putative inactive caspase B subunit p31 {ECO:0000305|PubMed:9857046};
DE Contains:
DE RecName: Full=Putative inactive caspase B subunit p17 {ECO:0000305|PubMed:9857046};
DE Contains:
DE RecName: Full=Putative inactive caspase subunit p14 {ECO:0000305|PubMed:9857046};
DE Flags: Precursor;
GN Name=csp-2 {ECO:0000303|PubMed:9857046, ECO:0000312|WormBase:Y73B6BL.7b};
GN ORFNames=Y73B6BL.7 {ECO:0000312|WormBase:Y73B6BL.7b};
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:AAC98296.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), FUNCTION, LACK OF CATALYTIC
RP ACTIVITY, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-8.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAC98296.1};
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 (ISOFORMS A AND B), INTERACTION WITH CED-3, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF 131-TRP--LEU-132; CYS-134 AND
RP PHE-186.
RX PubMed=19575016; DOI=10.1038/cdd.2009.88;
RA Geng X., Zhou Q.H., Kage-Nakadai E., Shi Y., Yan N., Mitani S., Xue D.;
RT "Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 autoactivation
RT and apoptosis in germ cells.";
RL Cell Death Differ. 16:1385-1394(2009).
RN [4] {ECO:0000305}
RP 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: [Isoform b]: Putative inactive caspase (PubMed:9857046). In
CC the germline, binds caspase ced-3 zymogen and prevents ced-3
CC autoactivation. Does not affect the caspase activity of mature ced-3
CC and ced-4-mediated mature ced-3 activation (PubMed:19575016).
CC Negatively regulates germline apoptosis by inhibiting autocleavage of
CC caspase ced-3 (PubMed:19575016). Involved in fertility
CC (PubMed:19575016). {ECO:0000269|PubMed:19575016,
CC ECO:0000269|PubMed:9857046}.
CC -!- FUNCTION: [Isoform a]: Putative inactive caspase (PubMed:9857046).
CC Dispensable for the inhibition of germline apoptosis (PubMed:19575016).
CC {ECO:0000269|PubMed:19575016, ECO:0000303|PubMed:9857046}.
CC -!- SUBUNIT: Interacts with ced-3 (via large subunit p17 or small subunit
CC p13); the interaction inhibits ced-3 autoactivation.
CC {ECO:0000269|PubMed:19575016}.
CC -!- SUBCELLULAR LOCATION: [Isoform b]: Cytoplasm
CC {ECO:0000269|PubMed:19575016}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=b {ECO:0000312|WormBase:Y73B6BL.7b};
CC IsoId=Q9TZP5-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y73B6BL.7a};
CC IsoId=Q9TZP5-2; Sequence=VSP_058807;
CC Name=c {ECO:0000312|WormBase:Y73B6BL.7c};
CC IsoId=Q9TZP5-3; Sequence=VSP_059611;
CC -!- TISSUE SPECIFICITY: Specifically expressed in the hermaphrodite
CC germline. {ECO:0000269|PubMed:19575016}.
CC -!- PTM: Cleavage by csp-1 isoform b or ced-3 removes the propeptide and
CC generates subunit p31 in vitro. An additional cleavage at Asp-149
CC generates the 2 subunits p17 and p14 but this cleavage appears to be
CC less efficient. {ECO:0000269|PubMed:9857046}.
CC -!- DISRUPTION PHENOTYPE: Survival of touch neurons and several pharyngeal
CC cells is not affected during development. In a ced-3 n2427 or ced-3
CC n2427 and cps-3 n4872 mutant background, no extra pharyngeal cells
CC caused by impaired apoptosis are produced. In a csp-3 n4872, csp-1
CC n4967 and ced-3 n3692 mutant background, pharyngeal cells, that are
CC normally fated to die, survive and 16 percent of animals have still 1
CC or more cell corpses that are morphologically apoptotic and are
CC internalized by engulfing cells. In addition, apoptosis of the male
CC linker cell occurs normally. {ECO:0000269|PubMed:23505386}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU003971}.
CC -!- CAUTION: Although the active site residues Cys and His are conserved,
CC appears to lack catalytic activity in vitro. This is probably due to
CC the active site pentapeptide VCCRG being highly divergent from the
CC canonical active site pentapeptide QAC[RQG]G present in catalytically
CC active caspases. {ECO:0000303|PubMed:9857046}.
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DR EMBL; AF088288; AAC98295.1; -; mRNA.
DR EMBL; AF088289; AAC98296.1; -; mRNA.
DR EMBL; BX284604; CCD74157.1; -; Genomic_DNA.
DR EMBL; BX284604; SIT60436.1; -; Genomic_DNA.
DR EMBL; BX284604; SIT60437.1; -; Genomic_DNA.
DR PIR; T43638; T43638.
DR RefSeq; NP_001023575.1; NM_001028404.2.
DR RefSeq; NP_001335546.1; NM_001348645.1.
DR RefSeq; NP_001335547.1; NM_001348644.1.
DR AlphaFoldDB; Q9TZP5; -.
DR SMR; Q9TZP5; -.
DR STRING; 6239.Y73B6BL.7; -.
DR MEROPS; C14.014; -.
DR EnsemblMetazoa; Y73B6BL.7a.1; Y73B6BL.7a.1; WBGene00000820. [Q9TZP5-2]
DR EnsemblMetazoa; Y73B6BL.7b.1; Y73B6BL.7b.1; WBGene00000820. [Q9TZP5-1]
DR EnsemblMetazoa; Y73B6BL.7c.1; Y73B6BL.7c.1; WBGene00000820. [Q9TZP5-3]
DR GeneID; 177391; -.
DR UCSC; Y73B6BL.7; c. elegans. [Q9TZP5-1]
DR CTD; 177391; -.
DR WormBase; Y73B6BL.7a; CE28270; WBGene00000820; csp-2. [Q9TZP5-2]
DR WormBase; Y73B6BL.7b; CE51898; WBGene00000820; csp-2. [Q9TZP5-1]
DR WormBase; Y73B6BL.7c; CE51881; WBGene00000820; csp-2. [Q9TZP5-3]
DR eggNOG; KOG0516; Eukaryota.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00970000196149; -.
DR HOGENOM; CLU_342972_0_0_1; -.
DR OrthoDB; 824788at2759; -.
DR Reactome; R-CEL-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-CEL-352238; Breakdown of the nuclear lamina.
DR PRO; PR:Q9TZP5; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00000820; Expressed in larva and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0097179; C:protease inhibitor complex; IMP:UniProtKB.
DR GO; GO:0089720; F:caspase binding; IPI: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:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0035375; F:zymogen binding; IDA: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:1990001; P:inhibition of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IGI:UniProtKB.
DR GO; GO:1904747; P:positive regulation of apoptotic process involved in development; IGI:UniProtKB.
DR GO; GO:0090727; P:positive regulation of brood size; IMP:UniProtKB.
DR GO; GO:1905516; P:positive regulation of fertilization; IGI:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
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 PANTHER; PTHR10454; PTHR10454; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 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; Cytoplasm; Reference proteome.
FT PROPEP 1..8
FT /note="Removed in mature form by cps-1 or ced-3"
FT /evidence="ECO:0000269|PubMed:9857046"
FT /id="PRO_0000439221"
FT CHAIN 9..263
FT /note="Putative inactive caspase B subunit p31"
FT /evidence="ECO:0000303|PubMed:9857046"
FT /id="PRO_0000439222"
FT CHAIN 9..149
FT /note="Putative inactive caspase B subunit p17"
FT /evidence="ECO:0000303|PubMed:9857046"
FT /id="PRO_0000439223"
FT CHAIN 150..263
FT /note="Putative inactive caspase subunit p14"
FT /evidence="ECO:0000303|PubMed:9857046"
FT /id="PRO_0000439224"
FT VAR_SEQ 1
FT /note="M -> MKIGWLLITICSGIITKCINAHSSPYQNANESAIDDAYFLVLIIPAV
FT SVAIVLVVVIFLCCPRQQIRSDNVIKLEEGVNDVIEENVTHVVSLREAKVSGMMTDLTR
FT FRQEIFTKHLTFNSNPESIDAATKNVQNVKQSLDTWRDRIKERLDEIDRLCTEEGDSLT
FT PEQYSALREMRRQLADEYDTVLRTVEGIHTRLNILSALLIEFSSVTSSMQSWMTDRARL
FT AGDIRHKSGDPMRVDEARFEAKSLMDEVVREESRLKTIGASVLKIEQEISAMRDDVRAS
FT RSTDDVGISMDEVYEKRRRVEVDYMQLLRQCQDLISLQIRLHAMNDEHAEQARRAEGWL
FT QMLKNDVAGVAKDPRFKKDEDLIERDEELNRMAAGGSGGPTSRQLAMREKIEQREREEE
FT EWRRKAKEKFEEEAAKNRARERKWAEEHGFNRPIRTRSQKYAEQDRIRYARKKAALEQS
FT NEQSNESTDDAVESDSDDVPAPQSPPTPSPADPGPTTSSSSLTQDPASNATGFSDVPAP
FT QAPPTPSPADPGPTTSSSSLTQDPASNATGFSGSSPPNSFEETRM (in isoform
FT a)"
FT /evidence="ECO:0000305"
FT /id="VSP_058807"
FT VAR_SEQ 1
FT /note="M -> MMTDLTRFRQEIFTKHLTFNSNPESIDAATKNVQNVKQSLDTWRDRI
FT KERLDEIDRLCTEEGDSLTPEQYSALREMRRQLADEYDTVLRTVEGIHTRLNILSALLI
FT EFSSVTSSMQSWMTDRARLAGDIRHKSGDPMRVDEARFEAKSLMDEVVREESRLKTIGA
FT SVLKIEQEISAMRDDVRASRSTDDVGISMDEVYEKRRRVEVDYMQLLRQCQDLISLQIR
FT LHAMNDEHAEQARRAEGWLQMLKNDVAGVAKDPRFKKDEDLIERDEELNRMAAGGSGGP
FT TSRQLAMREKIEQREREEEEWRRKAKEKFEEEAAKNRARERKWAEEHGFNRPIRTRSQK
FT YAEQDRIRYARKKAALEQSNEQSNESTDDAVESDSDDVPAPQSPPTPSPADPGPTTSSS
FT SLTQDPASNATGFSDVPAPQAPPTPSPADPGPTTSSSSLTQDPASNATGFSGSSPPNSF
FT EETRM (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059611"
FT MUTAGEN 8
FT /note="D->A: Loss of propeptide cleavage."
FT /evidence="ECO:0000269|PubMed:9857046"
FT MUTAGEN 131..132
FT /note="WL->ER: Loss of interaction with ced-3 small subunit
FT p13. Increased germline apoptosis in a ced-6 n2095 mutant
FT background, loss of interaction with ced-3 and loss of ced-
FT 3 autoactivation; when associated with D-186."
FT /evidence="ECO:0000269|PubMed:19575016"
FT MUTAGEN 134
FT /note="C->E: Reduction in the interaction with ced-3 small
FT subunit p13."
FT /evidence="ECO:0000269|PubMed:19575016"
FT MUTAGEN 186
FT /note="F->D: Severe reduction in the interaction with ced-3
FT large subunit p17. Increased germline apoptosis in a ced-6
FT n2095 mutant background, loss of interaction with ced-3 and
FT loss of ced-3 autoactivation; when associated with E-131
FT and R-132."
FT /evidence="ECO:0000269|PubMed:19575016"
SQ SEQUENCE 263 AA; 30401 MW; FE94EC95B8B59FEE CRC64;
MMCEDASDGK KIDETRKYRN NRSSKCRAII INNVVFCGME KRIGSDKDKK KLSKLFERLG
YQSTSYDNLK SSEILETVRQ FTQSNHGDSL IITIMSHGDQ GLLYGVDGVP VQMLDIIDLM
CTASLAKKPK WLMCVCCRGD RIDRAVRCDG FIDNFFDRFP KFFQFMKSKF PSHQTSSSQA
DLLVSFSTSP GFLSFRDETK GTWYIQELYR VIIENAKDTH LADLLMETNR RVVEKYEADK
VVIVCKQAPE FWSRFTKQLF FDV
