CAN_CAEEL
ID CAN_CAEEL Reviewed; 780 AA.
AC P34308; P34309; Q5DX51; Q5DX52;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 4.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Calpain clp-1;
DE EC=3.4.22.- {ECO:0000255|PROSITE-ProRule:PRU00239};
GN Name=clp-1 {ECO:0000312|WormBase:C06G4.2a};
GN ORFNames=C06G4.2 {ECO:0000312|WormBase:C06G4.2a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=7906398; DOI=10.1038/368032a0;
RA Wilson R., Ainscough R., Anderson K., Baynes C., Berks M., Bonfield J.,
RA Burton J., Connell M., Copsey T., Cooper J., Coulson A., Craxton M.,
RA Dear S., Du Z., Durbin R., Favello A., Fraser A., Fulton L., Gardner A.,
RA Green P., Hawkins T., Hillier L., Jier M., Johnston L., Jones M.,
RA Kershaw J., Kirsten J., Laisster N., Latreille P., Lightning J., Lloyd C.,
RA Mortimore B., O'Callaghan M., Parsons J., Percy C., Rifken L., Roopra A.,
RA Saunders D., Shownkeen R., Sims M., Smaldon N., Smith A., Smith M.,
RA Sonnhammer E., Staden R., Sulston J., Thierry-Mieg J., Thomas K.,
RA Vaudin M., Vaughan K., Waterston R., Watson A., Weinstock L.,
RA Wilkinson-Sproat J., Wohldman P.;
RT "2.2 Mb of contiguous nucleotide sequence from chromosome III of C.
RT elegans.";
RL Nature 368:32-38(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12410314; DOI=10.1038/nature01108;
RA Syntichaki P., Xu K., Driscoll M., Tavernarakis N.;
RT "Specific aspartyl and calpain proteases are required for neurodegeneration
RT in C. elegans.";
RL Nature 419:939-944(2002).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22253611; DOI=10.1371/journal.pgen.1002471;
RA Etheridge T., Oczypok E.A., Lehmann S., Fields B.D., Shephard F.,
RA Jacobson L.A., Szewczyk N.J.;
RT "Calpains mediate integrin attachment complex maintenance of adult muscle
RT in Caenorhabditis elegans.";
RL PLoS Genet. 8:E1002471-E1002471(2012).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22479198; DOI=10.1371/journal.pgen.1002602;
RA Joyce P.I., Satija R., Chen M., Kuwabara P.E.;
RT "The atypical calpains: evolutionary analyses and roles in Caenorhabditis
RT elegans cellular degeneration.";
RL PLoS Genet. 8:E1002602-E1002602(2012).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which
CC catalyzes limited proteolysis of substrates (By similarity). Required
CC for assembly and maintenance of integrin attachment complexes which are
CC essential for maintenance of adult muscle (PubMed:22253611).
CC Proteolytic activity is activated in response to increased
CC intracellular Ca(2+) levels during cell degeneration and promotes
CC necrotic cell death (PubMed:12410314, PubMed:22479198).
CC {ECO:0000250|UniProtKB:P07384, ECO:0000269|PubMed:12410314,
CC ECO:0000269|PubMed:22253611, ECO:0000269|PubMed:22479198}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, M line
CC {ECO:0000269|PubMed:22479198}. Cytoplasm, myofibril, sarcomere
CC {ECO:0000269|PubMed:22479198}. Note=In body wall muscle cells,
CC localizes at M-lines extending over the H-zone, and at adhesion plaques
CC which form between adjacent cells. {ECO:0000269|PubMed:22479198}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=a {ECO:0000312|WormBase:C06G4.2a};
CC IsoId=P34308-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:C06G4.2b};
CC IsoId=P34308-2; Sequence=VSP_005247, VSP_005252;
CC Name=c {ECO:0000312|WormBase:C06G4.2c};
CC IsoId=P34308-3; Sequence=VSP_005249, VSP_005251;
CC Name=d {ECO:0000312|WormBase:C06G4.2d};
CC IsoId=P34308-4; Sequence=VSP_005248, VSP_005250;
CC -!- TISSUE SPECIFICITY: Expressed in muscle and neuronal tissues
CC (PubMed:12410314, PubMed:22479198). Expressed in the ventral and dorsal
CC nerve cord, intestinal and hypodermal tissues (PubMed:22479198).
CC {ECO:0000269|PubMed:12410314, ECO:0000269|PubMed:22479198}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in adult muscle
CC defects which include irregularities in sarcomeric structures,
CC disorganized integrin attachment complexes, and increased mitochondrial
CC fragmentation (PubMed:22253611). RNAi-mediated knockdown in integrin
CC attachment complex component mutants unc-112 (e669su250) and unc-52
CC (r367) blocks the protein degradation which normally results from
CC complex disruption (PubMed:22253611). RNAi-mediated knockdown
CC suppresses cell death in the neurodegenerative models deg-3 (u662),
CC gsa-1 (Q227L) and mec-4 (u231) (PubMed:12410314).
CC {ECO:0000269|PubMed:12410314, ECO:0000269|PubMed:22253611}.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; BX284603; CCD63432.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD63433.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD63434.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD63435.1; -; Genomic_DNA.
DR PIR; S44749; S44749.
DR PIR; S44750; S44750.
DR RefSeq; NP_498740.2; NM_066339.5. [P34308-2]
DR RefSeq; NP_498741.3; NM_066340.4. [P34308-1]
DR RefSeq; NP_741237.1; NM_171886.4.
DR RefSeq; NP_741238.1; NM_171201.1.
DR AlphaFoldDB; P34308; -.
DR SMR; P34308; -.
DR BioGRID; 41328; 14.
DR STRING; 6239.C06G4.2a; -.
DR MEROPS; C02.A03; -.
DR EPD; P34308; -.
DR PaxDb; P34308; -.
DR PeptideAtlas; P34308; -.
DR EnsemblMetazoa; C06G4.2a.1; C06G4.2a.1; WBGene00000542. [P34308-1]
DR EnsemblMetazoa; C06G4.2a.2; C06G4.2a.2; WBGene00000542. [P34308-1]
DR EnsemblMetazoa; C06G4.2b.1; C06G4.2b.1; WBGene00000542. [P34308-2]
DR EnsemblMetazoa; C06G4.2b.2; C06G4.2b.2; WBGene00000542. [P34308-2]
DR EnsemblMetazoa; C06G4.2c.1; C06G4.2c.1; WBGene00000542. [P34308-3]
DR EnsemblMetazoa; C06G4.2d.1; C06G4.2d.1; WBGene00000542. [P34308-4]
DR GeneID; 176122; -.
DR KEGG; cel:CELE_C06G4.2; -.
DR UCSC; C06G4.2a.1; c. elegans. [P34308-1]
DR CTD; 176122; -.
DR WormBase; C06G4.2a; CE37743; WBGene00000542; clp-1. [P34308-1]
DR WormBase; C06G4.2b; CE37744; WBGene00000542; clp-1. [P34308-2]
DR WormBase; C06G4.2c; CE00517; WBGene00000542; clp-1. [P34308-3]
DR WormBase; C06G4.2d; CE30486; WBGene00000542; clp-1. [P34308-4]
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00970000196060; -.
DR InParanoid; P34308; -.
DR OMA; LYMHSAS; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; P34308; -.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR PRO; PR:P34308; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000542; Expressed in larva and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031430; C:M band; IDA:WormBase.
DR GO; GO:0030017; C:sarcomere; IDA:WormBase.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; IMP:UniProtKB.
DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:UniProtKB.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; IGI:WormBase.
DR GO; GO:0060298; P:positive regulation of sarcomere organization; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR InterPro; IPR033883; C2_III.
DR InterPro; IPR022684; Calpain_cysteine_protease.
DR InterPro; IPR022682; Calpain_domain_III.
DR InterPro; IPR022683; Calpain_III.
DR InterPro; IPR036213; Calpain_III_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Hydrolase; Protease; Reference proteome;
KW Thiol protease.
FT CHAIN 1..780
FT /note="Calpain clp-1"
FT /id="PRO_0000207734"
FT DOMAIN 316..611
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT REGION 269..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 371
FT /evidence="ECO:0000250|UniProtKB:Q07009"
FT ACT_SITE 527
FT /evidence="ECO:0000250|UniProtKB:Q07009"
FT ACT_SITE 551
FT /evidence="ECO:0000250|UniProtKB:Q07009"
FT VAR_SEQ 76..121
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_005247"
FT VAR_SEQ 77..113
FT /note="SNYDQGGNGNSGDQQKRKRDMAKDLIGGIFDNVVNRK -> IFIFKIVRQKF
FT PKNSSSFFCVRKHLDSLKTSPCGLDQ (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_005249"
FT VAR_SEQ 77..100
FT /note="SNYDQGGNGNSGDQQKRKRDMAKD -> GGGSGGGGGGNNIGSLVGSLIGGG
FT (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_005248"
FT VAR_SEQ 101..121
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_005250"
FT VAR_SEQ 114..780
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_005251"
FT VAR_SEQ 708
FT /note="D -> DMNN (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_005252"
SQ SEQUENCE 780 AA; 83643 MW; C1DFA4E5671F7835 CRC64;
MADDEEEIIQ KVEVKPDEFN GLIGSIAGNL IRDKVGGAGG DILGGLASNF FGGGGGGGGG
GGGGGFGGGN GGFGGGSNYD QGGNGNSGDQ QKRKRDMAKD LIGGIFDNVV NRKGKKEQDN
YGGGGNYGGG GGNQGGGGGG GFNFNDIGGL INSMGGGGGG GQRQGGGGGG FGDILGGIGS
LIGGGGGGQY NGGGGNVNPN NLNGGMVNVI GNLIGEAAHR FLGVDPGTGR IIGAVAGNVI
MGLGGKDNSL GNIGKVILDN IISGKFRRDV DPFVRPGPDP DRGGGGSGPS PISPRPTTEP
QDFYELRDQC LESKRLFEDP QFLANDSSLF FSKRPPKRVE WLRPGEITRE PQLITEGHSR
FDVIQGELGD CWLLAAAANL TLKDELFYRV VPPDQSFTEN YAGIFHFQFW QYGKWVDVVI
DDRLPTSNGE LLYMHSASNN EFWSALLEKA YAKLFGSYEA LKGGTTSEAL EDMTGGLTEF
IDLKNPPRNL MQMMMRGFEM GSLFGCSIEA DPNVWEAKMS NGLVKGHAYS ITGCRIVDGP
NGQTCILRIR NPWGNEQEWN GPWSDNSREW RSVPDSVKQD MGLKFDHDGE FWMSFDDFMR
NFEKMEICNL GPDVMDEVYQ MTGVKAAGMV WAANTHDGAW VRNQTAGGCR NYINTFANNP
QFRVQLTDSD PDDDDELCTV IFAVLQKYRR NLKQDGLDNV PIGFAVYDAG NNRGRLSKQF
FAANKSAMRS AAFINLREMT GRFRVPPGNY VVVPSTFEPN EEAEFMLRVY TNGFIESEEL
