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   27-MAR-2024, entry version 172.
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}.
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; 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; 15.
DR   STRING; 6239.C06G4.2a.2; -.
DR   MEROPS; C02.A03; -.
DR   EPD; P34308; -.
DR   PaxDb; 6239-C06G4-2a; -.
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   AGR; WB:WBGene00000542; -.
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; 142935at2759; -.
DR   PhylomeDB; P34308; -.
DR   PRO; PR:P34308; -.
DR   Proteomes; UP000001940; Chromosome III.
DR   Bgee; WBGene00000542; Expressed in larva and 4 other cell types or 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:0070266; P:necroptotic process; 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   Gene3D; 2.60.120.380; -; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 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   PANTHER; PTHR10183; CALPAIN; 1.
DR   PANTHER; PTHR10183:SF379; CALPAIN-A-RELATED; 1.
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; Calpain large subunit, middle domain (domain III); 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 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
//