CANA_DROME
ID CANA_DROME Reviewed; 828 AA.
AC Q11002; Q9V8U6; Q9V8U7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 18-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Calpain-A;
DE EC=3.4.22.-;
DE AltName: Full=Calcium-activated neutral proteinase A;
DE Short=CANP A;
DE Contains:
DE RecName: Full=Calpain-A catalytic subunit;
GN Name=CalpA; ORFNames=CG7563;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Canton-S; TISSUE=Larva;
RX PubMed=7929201; DOI=10.1016/s0021-9258(17)31508-9;
RA Emori Y., Saigo K.;
RT "Calpain localization changes in coordination with actin-related
RT cytoskeletal changes during early embryonic development of Drosophila.";
RL J. Biol. Chem. 269:25137-25142(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Canton-S;
RX PubMed=7823949; DOI=10.1128/mcb.15.2.824;
RA Theopold U., Pinter M., Daffre S., Tryselius Y., Friedrich P., Nassel D.R.,
RA Hultmark D.;
RT "CalpA, a Drosophila calpain homolog specifically expressed in a small set
RT of nerve, midgut, and blood cells.";
RL Mol. Cell. Biol. 15:824-834(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, ACTIVITY REGULATION, AND AUTOCATALYTIC
RP CLEAVAGE.
RX PubMed=10446155; DOI=10.1074/jbc.274.34.23893;
RA Jekely G., Friedrich P.;
RT "Characterization of two recombinant Drosophila calpains. CALPA and a novel
RT homolog, CALPB.";
RL J. Biol. Chem. 274:23893-23900(1999).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease. Involved in
CC the organization of the actin-related cytoskeleton during
CC embryogenesis. {ECO:0000269|PubMed:10446155,
CC ECO:0000269|PubMed:7929201}.
CC -!- ACTIVITY REGULATION: Activated by millimolar concentrations of calcium,
CC and by phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-
CC monophosphate, phosphatidylinositol and phosphatidic acid.
CC {ECO:0000269|PubMed:10446155}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7823949}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=B;
CC IsoId=Q11002-1; Sequence=Displayed;
CC Name=A;
CC IsoId=Q11002-2; Sequence=VSP_005244, VSP_005245;
CC -!- TISSUE SPECIFICITY: Localized to the anterior and posterior embryonic
CC poles just after fertilization. Becomes distributed around the polar
CC buds and just below the pole cells of the posterior pole during
CC cleavage cycles. During these nuclear divisions anterior localization
CC disappears. Localized to actin caps that underlie the plasma membrane,
CC immediately above each nucleus at cleavage cycles 8 and 9. Localized to
CC a small set of nerve, midgut and blood cells in adults.
CC {ECO:0000269|PubMed:7823949, ECO:0000269|PubMed:7929201}.
CC -!- PTM: Undergoes calcium-dependent autolytic cleavage between Lys-54 and
CC Asn-55, which is necessary for activation of the protein.
CC -!- MISCELLANEOUS: This protein binds calcium.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA55297.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X78555; CAA55298.1; -; mRNA.
DR EMBL; X78555; CAA55297.1; ALT_INIT; mRNA.
DR EMBL; Z46891; CAA86993.1; -; mRNA.
DR EMBL; Z46892; CAA86994.1; -; mRNA.
DR EMBL; AE013599; AAF57563.1; -; Genomic_DNA.
DR EMBL; AE013599; AAF57564.1; -; Genomic_DNA.
DR EMBL; AY051678; AAK93102.1; -; mRNA.
DR RefSeq; NP_001097378.1; NM_001103908.2. [Q11002-1]
DR RefSeq; NP_477047.1; NM_057699.5. [Q11002-1]
DR RefSeq; NP_477048.1; NM_057700.4. [Q11002-2]
DR AlphaFoldDB; Q11002; -.
DR SMR; Q11002; -.
DR BioGRID; 62895; 7.
DR DIP; DIP-23245N; -.
DR IntAct; Q11002; 1.
DR STRING; 7227.FBpp0085714; -.
DR MEROPS; C02.014; -.
DR SwissPalm; Q11002; -.
DR PaxDb; Q11002; -.
DR PRIDE; Q11002; -.
DR DNASU; 37232; -.
DR EnsemblMetazoa; FBtr0086529; FBpp0085714; FBgn0012051. [Q11002-1]
DR EnsemblMetazoa; FBtr0086530; FBpp0085715; FBgn0012051. [Q11002-2]
DR EnsemblMetazoa; FBtr0112869; FBpp0111782; FBgn0012051. [Q11002-1]
DR GeneID; 37232; -.
DR KEGG; dme:Dmel_CG7563; -.
DR CTD; 37232; -.
DR FlyBase; FBgn0012051; CalpA.
DR VEuPathDB; VectorBase:FBgn0012051; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000158966; -.
DR HOGENOM; CLU_010982_0_1_1; -.
DR InParanoid; Q11002; -.
DR OMA; EMNLIEW; -.
DR PhylomeDB; Q11002; -.
DR BRENDA; 3.4.22.B36; 1994.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 37232; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 37232; -.
DR PRO; PR:Q11002; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0012051; Expressed in second segment of antenna (Drosophila) and 52 other tissues.
DR ExpressionAtlas; Q11002; baseline and differential.
DR Genevisible; Q11002; DM.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; NAS:UniProtKB.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042335; P:cuticle development; IDA:FlyBase.
DR GO; GO:0050832; P:defense response to fungus; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IDA:FlyBase.
DR GO; GO:0008345; P:larval locomotory behavior; IMP:FlyBase.
DR GO; GO:0007520; P:myoblast fusion; IMP:FlyBase.
DR GO; GO:0016322; P:neuron remodeling; IMP:FlyBase.
DR GO; GO:0016540; P:protein autoprocessing; IDA:FlyBase.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
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; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
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 SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49758; SSF49758; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50203; CALPAIN_CAT; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 5.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autocatalytic cleavage; Calcium; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Protease;
KW Reference proteome; Repeat; Thiol protease.
FT CHAIN 1..828
FT /note="Calpain-A"
FT /id="PRO_0000026497"
FT CHAIN 55..828
FT /note="Calpain-A catalytic subunit"
FT /id="PRO_0000026498"
FT DOMAIN 1..14
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 88..387
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 579..614
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 699..734
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 729..764
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 764..799
FT /note="EF-hand 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 388..557
FT /note="Domain III"
FT REGION 558..577
FT /note="Linker"
FT REGION 578..828
FT /note="Domain IV"
FT ACT_SITE 143
FT /evidence="ECO:0000250"
FT ACT_SITE 299
FT /evidence="ECO:0000250"
FT ACT_SITE 327
FT /evidence="ECO:0000250"
FT BINDING 712
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 714
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 716
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 718
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 723
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 742
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 746
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 748
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 753
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT SITE 54..55
FT /note="Cleavage; by autolysis"
FT VAR_SEQ 554..565
FT /note="ENDDHVGYGGKA -> CVQVDNDNEFVY (in isoform A)"
FT /evidence="ECO:0000303|PubMed:7823949"
FT /id="VSP_005244"
FT VAR_SEQ 566..828
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:7823949"
FT /id="VSP_005245"
FT CONFLICT 35
FT /note="I -> Y (in Ref. 2; CAA86993/CAA86994)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="V -> I (in Ref. 2; CAA86994)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="N -> H (in Ref. 1; CAA55298/CAA55297)"
FT /evidence="ECO:0000305"
FT CONFLICT Q11002-2:554..565
FT /note="CVQVDNDNEFVY -> RTSRQ (in Ref. 2; CAA86994)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 828 AA; 93963 MW; 09576D1268BD569C CRC64;
MDDLRGFLRQ AGQEFLNAAG EAAMGAAKDV VGSVINEIFI KKEADTKRVL PSIKNMRVLG
EKSSSLGPYS EVQDYETILN SCLASGSLFE DPLFPASNES LQFSRRPDRH IEWLRPHEIA
ENPQFFVEGY SRFDVQQGEL GDCWLLAATA NLTQESNLFF RVIPAEQSFE ENYAGIFHFR
FWQYGKWVDV IIDDRLPTYN GELMYMHSTE KNEFWSALLE KAYAKLHGSY EALKGGSTCE
AMEDFTGGVS EWYDLKEAPG NLFTILQKAA ERNSMMGCSI EPDPNVTEAE TPQGLIRGHA
YSITKVCLID IVTPNRQGKI PMIRMRNPWG NEAEWNGPWS DSSPEWRYIP EEQKAEIGLT
FDRDGEFWMS FQDFLNHFDR VEICNLSPDS LTEDQQNSGK RKWEMSMYEG EWTPGVTAGG
CRNFLDTFWH NPQYIITLVD PDEEDEEGQC TVIVALMQKN RRSKRNMGME CLTIGFAIYS
LNDRELENRP QGLNFFRYKS SVGRSPHFIN TREVCARFKL PPGHYLIVPS TFDPNEEGEF
IIRVFSETQN NMEENDDHVG YGGKADTITP GFPTPKPIDP QKEGLRRLFD SIAGKDMEVD
WMELKRILDH SMRDDLPKPV VFNRFSNNMA FETQAAGPGD DGAGACGLLS LICGPFLKGT
PFEEQLGMND QSNKRLIGDN PADGGPVTAN AIVDETHGFS KDVCRSMVAM LDADKSGKLG
FEEFETLLSE IAKWKAIFKV YDVENTGRVS GFQLREALNS AGYHLNNRVL NVLGHRYGSR
DGKIAFDDFI MCAVKIKTYI DIFKERDTEK NETATFTLEE WIERTIYS
