CAN2_HUMAN
ID CAN2_HUMAN Reviewed; 700 AA.
AC P17655; A6NDG7; B7ZA96; E7ES58; Q16738; Q6PJT3; Q8WU26; Q9HBB1;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 6.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Calpain-2 catalytic subunit;
DE EC=3.4.22.53;
DE AltName: Full=Calcium-activated neutral proteinase 2;
DE Short=CANP 2;
DE AltName: Full=Calpain M-type;
DE AltName: Full=Calpain large polypeptide L2;
DE AltName: Full=Calpain-2 large subunit;
DE AltName: Full=Millimolar-calpain;
DE Short=M-calpain;
DE Flags: Precursor;
GN Name=CAPN2; Synonyms=CANPL2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-22.
RX PubMed=2852952; DOI=10.1021/bi00421a022;
RA Imajoh S., Aoki K., Ohno S., Emori Y., Kawasaki H., Sugihara H., Suzuki K.;
RT "Molecular cloning of the cDNA for the large subunit of the high-Ca2+-
RT requiring form of human Ca2+-activated neutral protease.";
RL Biochemistry 27:8122-8128(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-22.
RC TISSUE=Astrocytoma;
RX PubMed=10944468; DOI=10.1006/bbrc.2000.3282;
RA Ye Z., Connor J.R.;
RT "cDNA cloning by amplification of circularized first strand cDNAs reveals
RT non-IRE-regulated iron-responsive mRNAs.";
RL Biochem. Biophys. Res. Commun. 275:223-227(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-22; GLY-68; ARG-476;
RP GLN-521; GLN-568 AND GLN-677.
RG NIEHS SNPs program;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-22.
RC TISSUE=Pancreas, Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-79, AND VARIANTS GLU-22 AND GLY-68.
RC TISSUE=Lymph node;
RX PubMed=2539381; DOI=10.1016/s0021-9258(18)83364-6;
RA Hata A., Ohno S., Akita Y., Suzuki K.;
RT "Tandemly reiterated negative enhancer-like elements regulate transcription
RT of a human gene for the large subunit of calcium-dependent protease.";
RL J. Biol. Chem. 264:6404-6411(1989).
RN [8]
RP PROTEIN SEQUENCE OF 2-12.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP FUNCTION.
RX PubMed=17650508; DOI=10.1074/jbc.m609608200;
RA Sanchez-Sanchez F., Martinez-Redondo F., Aroca-Aguilar J.D.,
RA Coca-Prados M., Escribano J.;
RT "Characterization of the intracellular proteolytic cleavage of myocilin and
RT identification of calpain II as a myocilin-processing protease.";
RL J. Biol. Chem. 282:27810-27824(2007).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=10639123; DOI=10.1073/pnas.97.2.588;
RA Strobl S., Fernandez-Catalan C., Braun M., Huber R., Masumoto H.,
RA Nakagawa K., Irie A., Sorimachi H., Bourenkow G., Bartunik H., Suzuki K.,
RA Bode W.;
RT "The crystal structure of calcium-free human m-calpain suggests an
RT electrostatic switch mechanism for activation by calcium.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:588-592(2000).
RN [13]
RP VARIANT [LARGE SCALE ANALYSIS] GLU-22, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which
CC catalyzes limited proteolysis of substrates involved in cytoskeletal
CC remodeling and signal transduction. Proteolytically cleaves MYOC at
CC 'Arg-226' (PubMed:17650508). Proteolytically cleaves CPEB3 following
CC neuronal stimulation which abolishes CPEB3 translational repressor
CC activity, leading to translation of CPEB3 target mRNAs (By similarity).
CC {ECO:0000250|UniProtKB:O08529, ECO:0000269|PubMed:17650508}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity.; EC=3.4.22.53;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 7 Ca(2+) ions. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by 200-1000 micromolar concentrations of
CC calcium and inhibited by calpastatin.
CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit
CC (CAPNS1). Interacts with CPEB3; this leads to cleavage of CPEB3.
CC {ECO:0000250|UniProtKB:O08529, ECO:0000250|UniProtKB:Q07009}.
CC -!- INTERACTION:
CC P17655; P04632: CAPNS1; NbExp=5; IntAct=EBI-1028956, EBI-711828;
CC P17655; P55212: CASP6; NbExp=3; IntAct=EBI-1028956, EBI-718729;
CC P17655; P13473-2: LAMP2; NbExp=3; IntAct=EBI-1028956, EBI-21591415;
CC P17655; O60356: NUPR1; NbExp=3; IntAct=EBI-1028956, EBI-3908808;
CC P17655; P07237: P4HB; NbExp=3; IntAct=EBI-1028956, EBI-395883;
CC P17655; P60201-2: PLP1; NbExp=3; IntAct=EBI-1028956, EBI-12188331;
CC P17655; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-1028956, EBI-5280197;
CC P17655; P62826: RAN; NbExp=3; IntAct=EBI-1028956, EBI-286642;
CC P17655; Q9P1I4: ST13; NbExp=3; IntAct=EBI-1028956, EBI-25892254;
CC P17655; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-1028956, EBI-524753;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Translocates to
CC the plasma membrane upon Ca(2+) binding.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P17655-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P17655-2; Sequence=VSP_043027, VSP_043028;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH07686.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH11828.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/capn2/";
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DR EMBL; M23254; AAA35645.1; -; mRNA.
DR EMBL; AF261089; AAF99682.1; -; mRNA.
DR EMBL; AK316211; BAH14582.1; -; mRNA.
DR EMBL; AY835586; AAV80421.1; -; Genomic_DNA.
DR EMBL; AC096542; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC099065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007686; AAH07686.1; ALT_SEQ; mRNA.
DR EMBL; BC011828; AAH11828.1; ALT_SEQ; mRNA.
DR EMBL; BC021303; AAH21303.1; -; mRNA.
DR EMBL; J04700; AAA52760.1; -; Genomic_DNA.
DR CCDS; CCDS31035.1; -. [P17655-1]
DR CCDS; CCDS53478.1; -. [P17655-2]
DR PIR; S10590; CIHUH2.
DR RefSeq; NP_001139540.1; NM_001146068.1. [P17655-2]
DR RefSeq; NP_001739.2; NM_001748.4. [P17655-1]
DR PDB; 1KFU; X-ray; 2.50 A; L=2-700.
DR PDB; 1KFX; X-ray; 3.15 A; L=2-700.
DR PDB; 2NQA; X-ray; 2.20 A; A/B=48-346.
DR PDBsum; 1KFU; -.
DR PDBsum; 1KFX; -.
DR PDBsum; 2NQA; -.
DR AlphaFoldDB; P17655; -.
DR SMR; P17655; -.
DR BioGRID; 107274; 127.
DR ComplexPortal; CPX-2674; M-Calpain complex.
DR IntAct; P17655; 37.
DR MINT; P17655; -.
DR STRING; 9606.ENSP00000295006; -.
DR BindingDB; P17655; -.
DR ChEMBL; CHEMBL2382; -.
DR GuidetoPHARMACOLOGY; 2337; -.
DR MEROPS; C02.002; -.
DR GlyGen; P17655; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P17655; -.
DR MetOSite; P17655; -.
DR PhosphoSitePlus; P17655; -.
DR SwissPalm; P17655; -.
DR BioMuta; CAPN2; -.
DR DMDM; 317373596; -.
DR CPTAC; CPTAC-468; -.
DR CPTAC; CPTAC-469; -.
DR EPD; P17655; -.
DR jPOST; P17655; -.
DR MassIVE; P17655; -.
DR MaxQB; P17655; -.
DR PaxDb; P17655; -.
DR PeptideAtlas; P17655; -.
DR PRIDE; P17655; -.
DR ProteomicsDB; 53499; -. [P17655-1]
DR ProteomicsDB; 53500; -. [P17655-2]
DR Antibodypedia; 20748; 449 antibodies from 39 providers.
DR DNASU; 824; -.
DR Ensembl; ENST00000295006.6; ENSP00000295006.5; ENSG00000162909.18. [P17655-1]
DR Ensembl; ENST00000433674.6; ENSP00000413158.2; ENSG00000162909.18. [P17655-2]
DR GeneID; 824; -.
DR KEGG; hsa:824; -.
DR MANE-Select; ENST00000295006.6; ENSP00000295006.5; NM_001748.5; NP_001739.3.
DR UCSC; uc001hob.5; human. [P17655-1]
DR CTD; 824; -.
DR DisGeNET; 824; -.
DR GeneCards; CAPN2; -.
DR HGNC; HGNC:1479; CAPN2.
DR HPA; ENSG00000162909; Low tissue specificity.
DR MIM; 114230; gene.
DR neXtProt; NX_P17655; -.
DR OpenTargets; ENSG00000162909; -.
DR PharmGKB; PA26060; -.
DR VEuPathDB; HostDB:ENSG00000162909; -.
DR eggNOG; KOG0045; Eukaryota.
DR GeneTree; ENSGT00940000154784; -.
DR HOGENOM; CLU_010982_0_0_1; -.
DR InParanoid; P17655; -.
DR OMA; AFELCNI; -.
DR OrthoDB; 704215at2759; -.
DR PhylomeDB; P17655; -.
DR TreeFam; TF314748; -.
DR BRENDA; 3.4.22.53; 2681.
DR PathwayCommons; P17655; -.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
DR SignaLink; P17655; -.
DR SIGNOR; P17655; -.
DR BioGRID-ORCS; 824; 17 hits in 1076 CRISPR screens.
DR ChiTaRS; CAPN2; human.
DR EvolutionaryTrace; P17655; -.
DR GeneWiki; CAPN2; -.
DR GenomeRNAi; 824; -.
DR Pharos; P17655; Tchem.
DR PRO; PR:P17655; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P17655; protein.
DR Bgee; ENSG00000162909; Expressed in bronchial epithelial cell and 205 other tissues.
DR ExpressionAtlas; P17655; baseline and differential.
DR Genevisible; P17655; HS.
DR GO; GO:0110158; C:calpain complex; IPI:ComplexPortal.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0030864; C:cortical actin cytoskeleton; TAS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0031143; C:pseudopodium; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0008234; F:cysteine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0008092; F:cytoskeletal protein binding; NAS:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007520; P:myoblast fusion; IEA:Ensembl.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IEA:Ensembl.
DR GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR GO; GO:2001247; P:positive regulation of phosphatidylcholine biosynthetic process; IEA:Ensembl.
DR GO; GO:0016540; P:protein autoprocessing; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:BHF-UCL.
DR GO; GO:0032675; P:regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR CDD; cd00214; Calpain_III; 1.
DR CDD; cd00044; CysPc; 1.
DR CDD; cd16199; EFh_PEF_CAPN2; 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; IPR029539; CAPN2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR042736; EFh_PEF_CAPN2.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR001300; Peptidase_C2_calpain_cat.
DR PANTHER; PTHR10183:SF268; PTHR10183:SF268; 1.
DR Pfam; PF01067; Calpain_III; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR Pfam; PF00648; Peptidase_C2; 1.
DR PRINTS; PR00704; CALPAIN.
DR SMART; SM00720; calpain_III; 1.
DR SMART; SM00230; CysPc; 1.
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; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Calcium; Cell membrane;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Membrane; Metal-binding;
KW Protease; Reference proteome; Repeat; Thiol protease.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:22814378"
FT PROPEP 2..19
FT /note="Anchors to the small subunit"
FT /evidence="ECO:0000255"
FT /id="PRO_0000026487"
FT CHAIN 20..700
FT /note="Calpain-2 catalytic subunit"
FT /id="PRO_0000026488"
FT DOMAIN 45..344
FT /note="Calpain catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239"
FT DOMAIN 572..605
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 602..637
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 667..700
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 345..514
FT /note="Domain III"
FT REGION 515..529
FT /note="Linker"
FT REGION 530..700
FT /note="Domain IV"
FT ACT_SITE 105
FT /evidence="ECO:0000250"
FT ACT_SITE 262
FT /evidence="ECO:0000250"
FT ACT_SITE 286
FT /evidence="ECO:0000250"
FT BINDING 89
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 96
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 542
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 545
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 547
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 552
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 585
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 587
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 589
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 591
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 596
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 615
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 617
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 619
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 621
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 626
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 658
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 661
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 1..78
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043027"
FT VAR_SEQ 79
FT /note="T -> M (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043028"
FT VARIANT 22
FT /note="D -> E (in dbSNP:rs25655)"
FT /evidence="ECO:0000269|PubMed:10944468,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2539381,
FT ECO:0000269|PubMed:2852952, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:21269460"
FT /id="VAR_014435"
FT VARIANT 68
FT /note="S -> G (in dbSNP:rs2230083)"
FT /evidence="ECO:0000269|PubMed:2539381, ECO:0000269|Ref.4"
FT /id="VAR_021404"
FT VARIANT 476
FT /note="K -> R (in dbSNP:rs9804140)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021405"
FT VARIANT 521
FT /note="E -> Q (in dbSNP:rs28370127)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021406"
FT VARIANT 568
FT /note="K -> Q (in dbSNP:rs17599)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_014436"
FT VARIANT 677
FT /note="K -> Q (in dbSNP:rs2230082)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_021407"
FT CONFLICT 73..74
FT /note="IE -> MR (in Ref. 1; AAA35645)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="Q -> K (in Ref. 2; AAF99682)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="N -> S (in Ref. 2; AAF99682)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="F -> V (in Ref. 1; AAA35645 and 2; AAF99682)"
FT /evidence="ECO:0000305"
FT HELIX 4..16
FT /evidence="ECO:0007829|PDB:1KFU"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 32..42
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 60..68
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:1KFX"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:1KFX"
FT HELIX 105..115
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 118..124
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 136..144
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 146..155
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 169..175
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 177..189
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:2NQA"
FT TURN 204..206
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 224..233
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 264..274
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 277..285
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 302..306
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 309..315
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 321..327
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 328..334
FT /evidence="ECO:0007829|PDB:2NQA"
FT STRAND 336..341
FT /evidence="ECO:0007829|PDB:2NQA"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:1KFU"
FT TURN 367..370
FT /evidence="ECO:0007829|PDB:1KFU"
FT TURN 378..380
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 406..413
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 420..425
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 429..435
FT /evidence="ECO:0007829|PDB:1KFU"
FT TURN 442..444
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 450..455
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:1KFX"
FT STRAND 466..471
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 479..492
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 495..505
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 507..509
FT /evidence="ECO:0007829|PDB:1KFX"
FT STRAND 527..530
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 533..541
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 542..546
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 550..560
FT /evidence="ECO:0007829|PDB:1KFU"
FT TURN 561..564
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 574..582
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 586..588
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 595..612
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 622..624
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 627..630
FT /evidence="ECO:0007829|PDB:1KFU"
FT TURN 631..635
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 640..650
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 655..657
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 659..679
FT /evidence="ECO:0007829|PDB:1KFU"
FT STRAND 687..690
FT /evidence="ECO:0007829|PDB:1KFU"
FT HELIX 691..698
FT /evidence="ECO:0007829|PDB:1KFU"
SQ SEQUENCE 700 AA; 79995 MW; 8CF8294351A024E3 CRC64;
MAGIAAKLAK DREAAEGLGS HDRAIKYLNQ DYEALRNECL EAGTLFQDPS FPAIPSALGF
KELGPYSSKT RGIEWKRPTE ICADPQFIIG GATRTDICQG ALGDCWLLAA IASLTLNEEI
LARVVPLNQS FQENYAGIFH FQFWQYGEWV EVVVDDRLPT KDGELLFVHS AEGSEFWSAL
LEKAYAKING CYEALSGGAT TEGFEDFTGG IAEWYELKKP PPNLFKIIQK ALQKGSLLGC
SIDITSAADS EAITFQKLVK GHAYSVTGAE EVESNGSLQK LIRIRNPWGE VEWTGRWNDN
CPSWNTIDPE ERERLTRRHE DGEFWMSFSD FLRHYSRLEI CNLTPDTLTS DTYKKWKLTK
MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDEED GESGCTFLVG LIQKHRRRQR
KMGEDMHTIG FGIYEVPEEL SGQTNIHLSK NFFLTNRARE RSDTFINLRE VLNRFKLPPG
EYILVPSTFE PNKDGDFCIR VFSEKKADYQ AVDDEIEANL EEFDISEDDI DDGFRRLFAQ
LAGEDAEISA FELQTILRRV LAKRQDIKSD GFSIETCKIM VDMLDSDGSG KLGLKEFYIL
WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKMPC QLHQVIVARF ADDQLIIDFD
NFVRCLVRLE TLFKIFKQLD PENTGTIELD LISWLCFSVL
