CAN5_CAEEL
ID CAN5_CAEEL Reviewed; 648 AA.
AC Q22036;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Calpain-5;
DE EC=3.4.22.- {ECO:0000269|PubMed:10783162};
DE AltName: Full=Sex-determining transformer protein 3;
GN Name=tra-3 {ECO:0000312|WormBase:LLC1.1};
GN Synonyms=clp-5 {ECO:0000312|WormBase:LLC1.1};
GN ORFNames=LLC1.1 {ECO:0000312|WormBase:LLC1.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000312|EMBL:AAB60256.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAB60256.1};
RX PubMed=8887539; DOI=10.1002/j.1460-2075.1996.tb00825.x;
RA Barnes T.M., Hodgkin J.;
RT "The tra-3 sex determination gene of Caenorhabditis elegans encodes a
RT member of the calpain regulatory protease family.";
RL EMBO J. 15:4477-4484(1996).
RN [2] {ECO:0000312|EMBL:CAB05248.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAB05248.1};
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, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-83.
RX PubMed=10783162;
RA Sokol S.B., Kuwabara P.E.;
RT "Proteolysis in Caenorhabditis elegans sex determination: cleavage of TRA-
RT 2A by TRA-3.";
RL Genes Dev. 14:901-906(2000).
RN [4]
RP FUNCTION, 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 [5]
RP 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).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF 126-TRP--LEU-648.
RX PubMed=26795495; DOI=10.1371/journal.ppat.1005389;
RA Zhang F., Peng D., Cheng C., Zhou W., Ju S., Wan D., Yu Z., Shi J.,
RA Deng Y., Wang F., Ye X., Hu Z., Lin J., Ruan L., Sun M.;
RT "Bacillus thuringiensis Crystal Protein Cry6Aa Triggers Caenorhabditis
RT elegans Necrosis Pathway Mediated by Aspartic Protease (ASP-1).";
RL PLoS Pathog. 12:E1005389-E1005389(2016).
CC -!- FUNCTION: Required for the correct female sexual development of the
CC soma and germline in hermaphrodite animals, while being fully
CC dispensable in males. Has calcium-dependent proteolytic activity and is
CC involved in the cleavage of tra-2, for which it acts as a potentiator.
CC Capable of calcium-dependent autolysis (PubMed:10783162). Part of the
CC necrosis cell death pathway (PubMed:12410314). Required for necrosis of
CC intestinal cells induced by B.thuringiensis endotoxin Cry6Aa
CC (PubMed:26795495). {ECO:0000269|PubMed:10783162,
CC ECO:0000269|PubMed:12410314, ECO:0000269|PubMed:26795495}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 3 Ca(2+) ions. {ECO:0000250};
CC -!- TISSUE SPECIFICITY: Expressed in neuronal, but not in GABA-ergic
CC neurons, intestinal, hypodermal and excretory tissues.
CC {ECO:0000269|PubMed:22479198}.
CC -!- DOMAIN: The calpain catalytic domain is essential for in vivo function
CC to promote female sexual development.
CC -!- DOMAIN: The C2 domain associated with the domain III is primarily
CC responsible for calcium binding.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown prevents neuronal
CC degeneration in a mec-4(u231), deg-1(u38) or gsa-1 gain-of-function
CC mutant background. {ECO:0000269|PubMed:12410314}.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
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DR EMBL; AH005324; AAB60256.1; -; Genomic_DNA.
DR EMBL; U12516; AAB60256.1; JOINED; Genomic_DNA.
DR EMBL; U12920; AAB60256.1; JOINED; Genomic_DNA.
DR EMBL; BX284604; CAB05248.1; -; Genomic_DNA.
DR PIR; S71885; S71885.
DR RefSeq; NP_502751.1; NM_070350.4.
DR AlphaFoldDB; Q22036; -.
DR SMR; Q22036; -.
DR BioGRID; 43468; 1.
DR STRING; 6239.LLC1.1; -.
DR MEROPS; C02.009; -.
DR iPTMnet; Q22036; -.
DR EPD; Q22036; -.
DR PaxDb; Q22036; -.
DR PeptideAtlas; Q22036; -.
DR PRIDE; Q22036; -.
DR EnsemblMetazoa; LLC1.1a.1; LLC1.1a.1; WBGene00006606.
DR GeneID; 178385; -.
DR KEGG; cel:CELE_LLC1.1; -.
DR UCSC; LLC1.1; c. elegans.
DR CTD; 178385; -.
DR WormBase; LLC1.1; CE16260; WBGene00006606; tra-3.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000172628; -.
DR HOGENOM; CLU_010982_3_2_1; -.
DR InParanoid; Q22036; -.
DR OMA; ICHIVNT; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; Q22036; -.
DR PRO; PR:Q22036; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00006606; Expressed in embryo and 4 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; ISS:WormBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:WormBase.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0019099; P:female germ-line sex determination; IMP:UniProtKB.
DR GO; GO:0042004; P:feminization of hermaphrodite soma; IMP:UniProtKB.
DR GO; GO:0042001; P:hermaphrodite somatic sex determination; IMP:WormBase.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IDA:WormBase.
DR GO; GO:0012501; P:programmed cell death; IEA:UniProtKB-KW.
DR GO; GO:0016540; P:protein autoprocessing; IDA:WormBase.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR CDD; cd04046; C2_Calpain; 1.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR033884; C2_Calpain.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
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; SM00239; C2; 1.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Calcium; Differentiation; Hydrolase; Necrosis;
KW Protease; Reference proteome; Sexual differentiation; Thiol protease.
FT CHAIN 1..648
FT /note="Calpain-5"
FT /id="PRO_0000207716"
FT DOMAIN 28..353
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 502..625
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 354..509
FT /note="Domain III"
FT ACT_SITE 83
FT /evidence="ECO:0000269|PubMed:10783162"
FT ACT_SITE 252
FT /evidence="ECO:0000250|UniProtKB:Q07009"
FT ACT_SITE 290
FT /evidence="ECO:0000250|UniProtKB:Q07009"
FT MUTAGEN 83
FT /note="C->S: Loss of tra-2 (isoform a) cleavage. Prevents
FT female sexual development."
FT /evidence="ECO:0000269|PubMed:10783162"
FT MUTAGEN 126..648
FT /note="Missing: Reduces susceptibility to B.thuringiensis
FT endotoxin Cry6Aa."
FT /evidence="ECO:0000269|PubMed:26795495"
SQ SEQUENCE 648 AA; 73614 MW; F6F56265FDCB80EC CRC64;
MTRSEKTRHF GNQNYEKLRK ICIKKKQPFV DTLFPPTNQS LFLEQRQSSD IVWKRPGELH
PDPHLFVEGA SPNDVTQGIL GNCWFVSACS ALTHNFKLLA QVIPDADDQE WSTKHAYAGI
FRFRFWRFGK WVEVVIDDLL PTRDGKLLFA RSKTPNEFWS ALLEKAFAKL YGCYENLVGG
HLSDALQDVS GGVAETLHVR KFLKDDPNDT ELKLFNDLKT AFDKGALVVA AIAARTKEEI
EESLDCGLVK GHAYAVSAVC TIDVTNPNER SFTSFIMGSK RKQNLIRLQN PWGEKEWNGA
WSDDSPEWQN VSASQLSTMG VQPANSDSDD GDFWMPWESF VHYFTDISLC QLFNTSVFSF
SRSYDEQIVF SEWTTNGKKS GAPDDRAGGC HNFKATFCNN PQYIFDIPSP NCSVMFALIQ
NDPSEGLKKR EPFVTIGMHV MKVENNRQYR VHTAMHPIAI SDYASGRSVY LHLQSLPRGR
YLLIPTTFAP KEQTLFMLRV YSDEHIHFSP LTKHAPKLGL LKCKSAQSVT RLTIHGVDFN
SASTGTHNVY AILKDSRKSF RTKTLSGVKS IQWDEQFLFH KSKNRQQYKI EVWEDRKMAR
DHLLAQSVII ALIDNENRDT TLQLTDPRGT VIGTVSVTVS AFDDPMYL
