3.4.22.54 26S proteasome regulatory subunit 6A + H2O - Homo sapiens ? - ? 390677 3.4.22.54 AHNAK nucleoprotein + H2O - Homo sapiens ? - ? 390167 3.4.22.54 AHNAK nucleoprotein + H2O AHNAK is lost in cells expressing active CAPN3. Conversely, AHNAK accumulates when calpain 3 is defective in skeletal muscle of calpainopathy patients Homo sapiens ? - ? 390167 3.4.22.54 AHNAK-N peptide + H2O a putative cleavage site is AHNAK-C2.2 Homo sapiens ? - ? 418445 3.4.22.54 ALDOA protein + H2O - Homo sapiens ? - ? 449541 3.4.22.54 aldolase A + H2O not an in vivo substrate or not detectable in total cell extracts Mus musculus ? - ? 404255 3.4.22.54 alpha-actinin-3 + H2O - Rattus norvegicus ? - ? 410712 3.4.22.54 alpha-fodrin + H2O - Rattus norvegicus ? - ? 410714 3.4.22.54 ANKRD23/CARP/MARP1 protein + H2O - Homo sapiens ? - ? 449571 3.4.22.54 annexin A1 + H2O - Homo sapiens ? - ? 391291 3.4.22.54 annexin A2 + H2O - Homo sapiens ? - ? 391292 3.4.22.54 annexin A7 + H2O - Homo sapiens ? - ? 391293 3.4.22.54 beta-catenin + H2O - Mus musculus ? - ? 361977 3.4.22.54 beta-catenin + H2O calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis Mus musculus ? - ? 361977 3.4.22.54 beta-oxidation enzyme + H2O - Homo sapiens ? - ? 449680 3.4.22.54 C/EBPa protein + H2O - Homo sapiens ? - ? 449721 3.4.22.54 calpastatin + H2O - Mus musculus ? - ? 381611 3.4.22.54 cardiac ankyrin repeat protein + H2O - Homo sapiens ? - ? 418536 3.4.22.54 connectin + H2O p94 binds to connectin at multiple sites including loci in the N2A and PEVK regions of connectin. Functionally, p94-N2A interactions suppress p94 autolysis and protected connectin from proteolysis. Dynamic nature of connectin molecule as a regulatory scaffold of p94 functions Homo sapiens ? - ? 390192 3.4.22.54 connectin + H2O p94 binds to connectin at multiple sites including loci in the N2A and PEVK regions of connectin. Functionally, p94-N2A interactions suppress p94 autolysis and protected connectin from proteolysis. Dynamic nature of connectin molecule as a regulatory scaffold of p94 functions Mus musculus ? - ? 390192 3.4.22.54 CTBP1 protein + H2O i.e. C-terminal binding protein 1 Homo sapiens ? - ? 449786 3.4.22.54 cyclin A + H2O - Mus musculus ? - ? 363683 3.4.22.54 cyclin A + H2O - Homo sapiens ? - ? 363683 3.4.22.54 cyclin A + H2O calpain 3-mediated cleavage of cyclin A in dividing myeloid pregenitor cells is important for the onset of differentiation Mus musculus additional information production of a truncated product that lacks the N-terminal destruction box required for its degradation at the end of mitosis. The cleaved form of cyclin A retains the cyclin-dependent kinase binding domain and forms active complexes with cdk2 ? 370640 3.4.22.54 cyclin A + H2O calpain 3-mediated cleavage of cyclin A in dividing myeloid pregenitor cells is important for the onset of differentiation Homo sapiens additional information production of a truncated product that lacks the N-terminal destruction box required for its degradation at the end of mitosis. The cleaved form of cyclin A retains the cyclin-dependent kinase binding domain and forms active complexes with cdk2 ? 370640 3.4.22.54 eukaryotic elongation factor 1-alpha 1 + H2O - Homo sapiens ? - ? 391947 3.4.22.54 eukaryotic elongation factor 1-alpha 2 + H2O - Homo sapiens ? - ? 391948 3.4.22.54 eukaryotic elongation factor 2 + H2O - Homo sapiens ? - ? 391949 3.4.22.54 eukaryotic translation initiation factor 3 subunit 7 + H2O - Homo sapiens ? - ? 391950 3.4.22.54 ezrin + H2O - Homo sapiens ? - ? 381857 3.4.22.54 filamin C + H2O - Homo sapiens ? - ? 363682 3.4.22.54 filamin C + H2O enzyme specifically cleaves the C-terminal portion Mus musculus ? - ? 363682 3.4.22.54 filamin C + H2O enzyme specifically cleaves the C-terminal portion Rattus norvegicus ? - ? 363682 3.4.22.54 filamin C + H2O enzyme specifically cleaves the C-terminal portion in living cells. Filamin C may be an in vivo substrate to c3, functioning to regulate protein-protein interactions with the sarcoglycans Mus musculus ? - ? 363682 3.4.22.54 filamin C + H2O enzyme specifically cleaves the C-terminal portion in living cells. Filamin C may be an in vivo substrate to c3, functioning to regulate protein-protein interactions with the sarcoglycans Rattus norvegicus ? - ? 363682 3.4.22.54 filamin-A + H2O - Homo sapiens ? - ? 391980 3.4.22.54 fodrin + H2O - Mus musculus ? - ? 405166 3.4.22.54 fructose bisphosphatealdolase A + H2O - Homo sapiens ? - ? 391997 3.4.22.54 glyceraldehyde-3-phosphate dehydrogenase + H2O - Homo sapiens ? - ? 95040 3.4.22.54 HSP60 + H2O - Mus musculus ? - ? 405438 3.4.22.54 IkappaB protein + H2O - Homo sapiens ? - ? 450069 3.4.22.54 importin-7 + H2O - Homo sapiens ? - ? 392247 3.4.22.54 M-cadherin + H2O - Mus musculus ? - ? 383236 3.4.22.54 M-cadherin + H2O calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis Mus musculus ? - ? 383236 3.4.22.54 MARP2/Ankrd2 + H2O - Homo sapiens ? - ? 390254 3.4.22.54 MARP2/Ankrd2 + H2O - Mus musculus ? - ? 390254 3.4.22.54 additional information a small in-frame deletion within the protease domain of muscle-specific calpain, p94 causes early-onset limb-girdle muscular dystrophy 2A Homo sapiens ? - ? 89 3.4.22.54 additional information the enzyme is associated with limb-girdle muscular dystrophy 2A Mus musculus ? - ? 89 3.4.22.54 additional information mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A Homo sapiens ? - ? 89 3.4.22.54 additional information limb-girdle muscular dystrophy type 2A is an autosomal recessive disorder characterized by selective atrophy of the proximal limb muscles. Its occurence is correlated, in a large number of patients, with defects ihn the human CAP3 gene. The most calpain 3 missense mutations are clustered in three areas that appear to affect intramolecular domain interactions and may impair the assembly and activation of this multi-domain protein Homo sapiens ? - ? 89 3.4.22.54 additional information important protein for normal muscle function. Mutations in the c3 gene result in limb-girdle muscular dystrophy type 2A Mus musculus ? - ? 89 3.4.22.54 additional information important protein for normal muscle function. Mutations in the c3 gene result in limb-girdle muscular dystrophy type 2A Rattus norvegicus ? - ? 89 3.4.22.54 additional information muscular dystrophy caused by mutations in CANP3 is found in patients from all countries examined so far Homo sapiens ? - ? 89 3.4.22.54 additional information two siblings originating from Reunion Island are affected by a limb-girdle muscular dystrophy type 2A and carry the same two mutations in the calpain gene: 946-1 AGtoAA, affecting a splice site, and S744G. They demonstrate the clinical variability possible with calpain-3 mutations Homo sapiens ? - ? 89 3.4.22.54 additional information autosomal recessive limb girdle muscular dystrophy is a clinically and genetically heterogenous group of diseases involving at least six different loci. Five genes have already been identified: calpain-3 at LGMD2A (15q15), and four members of the sarcoglycan (SG) complex, alpha-SG at LGMD2D (17q21), beta-SG at LGMD2E (4q12), gamma-SG at LGMD2C (13q12), and delta-SG at LGMD2F (5q33-q34). The gene product at LGMD2B (2p13-p16) is still unknown and at least one other gene is still unmapped Homo sapiens ? - ? 89 3.4.22.54 additional information limb-girdle muscular dystrophy: epidemiological study in Guipuzcoa, a small mountainous Basque province in northern Spain, finds the highest prevalence rate of LGMD described so far, 69 per million. Genetic studies demonstrate that 38 cases corresponde to the LGMD2A type, due to calpain-3 gene mutations. The particular calpain-3 mutation predominant in Basque chromosomes, exon 22, 2362AGtoTCATCT, has only been rarely found in the rest of the world. The clinical characteristics of the patients with calpain-3 gene mutations. The disease onset is between the ages of 8 and 15 years, in most cases in the pelvic girdle, and the patients become wheelchair-bound between 11 and 28 years after onset Homo sapiens ? - ? 89 3.4.22.54 additional information limb-girdle muscular dystrophy type 2A is an autosomal recessive disorder characterized mainly by symmetrical and selective atrophy of the proximal limb muscles. It derives from defects in the human CAPN3 gene. 97 distinct pathogenic calpain 3 mutations have been identified. The mutations are distributed along the entire length of the CAPN3 gene Homo sapiens ? - ? 89 3.4.22.54 additional information the selective distribution of the enzyme in T-lymphocytes, B-lymphocytes and natural killer cells , might be related to a specific function of this protease isoform in cells involved in the immune response Homo sapiens ? - ? 89 3.4.22.54 additional information calpain 3/p94 is not involved in postmortem proteolysis Mus musculus ? - ? 89 3.4.22.54 additional information loss-of-function mutations in the calpain 3 gene are associated with limb-girdle muscular dystrophy type 2A. Through the absence of cleavage of the cytoskeletal proteins, calpain 3 deficiency leads to abnormal sarcomers, impairment of muscle contractile capacity and death of muscle fibers Homo sapiens ? - ? 89 3.4.22.54 additional information neither the reduction of calpain 3 nor its aberrant activity is responsible for the muscular dystrophy with myositis (mdm). Overexpression of calpain 3 exacerbates muscular dystrophy with myositis (mdm) Mus musculus ? - ? 89 3.4.22.54 additional information skeletal muscle-specific calpain participates in the regulation of the conventional calpain-calpastatin system in skeletal muscle Mus musculus ? - ? 89 3.4.22.54 additional information cytoskeletal proteins are one class of its substrates Homo sapiens ? - ? 89 3.4.22.54 additional information NF-kappaB-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3 Homo sapiens ? - ? 89 3.4.22.54 additional information p94 is involved in regulation of the eukaryote protein synthesis system Homo sapiens ? - ? 89 3.4.22.54 additional information p94 proteolytic activity is involved in responses to muscle conditions, p94 inactivation causes limb-girdle muscular dystrophy Homo sapiens ? - ? 89 3.4.22.54 additional information p94 proteolytic activity is involved in responses to muscle conditions, p94 inactivation causes limb-girdle muscular dystrophy Mus musculus ? - ? 89 3.4.22.54 additional information calpain-3 does not cleave acetyl-coenzyme A acyltransferase, carnitine O-palmitoyl transferase II, carnitine acetyltransferase, and trifunctional protein alpha subunit Mus musculus ? - ? 89 3.4.22.54 additional information calpain 3 does not cleave PIAS4 Homo sapiens ? - ? 89 3.4.22.54 MyoD + H2O calpain 3 down-regulates MyoD protein levels Mus musculus ? - ? 412471 3.4.22.54 MyoD protein + H2O - Homo sapiens ? - ? 450308 3.4.22.54 myosin light chain 1 + H2O - Mus musculus ? - ? 385202 3.4.22.54 p94 + H2O best substrate for p94 is p94 itself Homo sapiens ? - ? 393159 3.4.22.54 PIAS3 + H2O - Homo sapiens ? - ? 418025 3.4.22.54 ryanodine receptor + H2O - Mus musculus ? - ? 410993 3.4.22.54 spectrin + H2O - Homo sapiens ? - ? 362513 3.4.22.54 succinyl-leucine-tyrosine-aminomethylcoumarin + H2O - Homo sapiens ? - ? 382848 3.4.22.54 talin + H2O - Homo sapiens ? - ? 358996 3.4.22.54 thioredoxin + H2O - Homo sapiens ? - ? 393662 3.4.22.54 titin + H2O - Mus musculus ? - ? 380771 3.4.22.54 titin + H2O - Homo sapiens ? - ? 380771 3.4.22.54 titin + H2O - Sus scrofa ? - ? 380771 3.4.22.54 titin + H2O - Bos taurus ? - ? 380771 3.4.22.54 titin + H2O calpain 3 expression is required for normal myofibril formation. Calpain 3 may influence the role of titin in sarcomere formation through proteolytic cleavage. The limb girdle muscular dystrophy 2A mutations in calpain C3 influence binding of calpain C3 to titin Mus musculus ? - ? 380771 3.4.22.54 titin + H2O the enzyme binds the C-terminus of titin at recognition motifs [LIMV]X(3,4) [LIMV]X(2)[LIMV][DE] and [LIMV]X(3,4)[LIMVA]X(2)[LIMV][DE] Homo sapiens ? - ? 380771 3.4.22.54 titin + H2O the enzyme binds the C-terminus of titin at recognition motifs [LIMV]X(3,4) [LIMV]X(2)[LIMV][DE] and [LIMV]X(3,4)[LIMVA]X(2)[LIMV][DE] Mus musculus ? - ? 380771 3.4.22.54 triosephosphate isomerase + H2O - Homo sapiens ? - ? 393716 3.4.22.54 tropomyosin + H2O - Rattus norvegicus ? - ? 366700 3.4.22.54 troponin I + H2O - Rattus norvegicus ? - ? 366701 3.4.22.54 troponins T + H2O - Rattus norvegicus ? - ? 411042 3.4.22.54 very long chain acyl-coenzyme A dehydrogenase + H2O an in vivo substrate for calpain-3 Mus musculus ? - ? 413055 3.4.22.54 vimentin + H2O - Homo sapiens ? - ? 393820 3.4.22.54 vinexin + H2O - Homo sapiens ? - ? 382962