Summary for peptidase C02.002: calpain-2

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namecalpain-2
Other namesCa2+-activated neutral protease, calpain II, calpain xCL-2 (Xenopus laevis), CAPN2 g.p. (Homo sapiens), milli-calpain, m-calpain
Domain architecture
MEROPS Classification
Classification Clan CA >> Subclan (none) >> Family C2 >> Subfamily A >> C02.002
Holotypecalpain-2 (Homo sapiens), Uniprot accession P17655 (peptidase unit: 75-327), MERNUM MER0000964
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00078
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.53
EnzymologyBRENDA database
Proteolytic eventsCutDB database (112 cleavages)
Activity statushuman: active (Sorimachi, 2004)
mouse: active (Azuma et al., 2003)
PhysiologyCalcium-dependent degradation of cytoskeletal proteins in mammalian cytosol. Implicated in anoxic neuronal cell death in stroke and spinal injuries.
KnockoutIn mouse, homozygous disruption of the gene for the calpain small subunit common to mu- and m-calpain eliminated both activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis. However, mutant embryos died at mid-gestation and displayed defects in the cardiovascular system, haemorrhaging, and accumulation of erythroid progenitors (Arthur et al., 2000). Experiments with RNAi and chemical inhibitors have indicated that calpain-2 plays an essential role in mitosis in cells in vitro (Honda et al., 2003).
Pharmaceutical relevanceA drug target for stroke and neural injuries (Huang & Wang, 2001). Also, calpain-mediated proteolysis may be a contributing factor in the insolubilization of crystallins occurring during normal maturation of lens or during cataract formation (Shih et al., 2001).
Pathways KEGGAlzheimer's disease
KEGGApoptosis
KEGGFocal adhesion
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Calpain-2
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/l/-Scissile bond-/-/-/- (based on 452 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 17 34 12 37 29 32 16 35
Pro 42 45 11 8 19 43 87 66
Ala 46 33 12 33 66 42 38 34
Val 25 31 48 12 24 21 29 21
Leu 29 37 124 25 31 36 23 25
Ile 8 10 27 5 7 17 10 11
Met 7 9 6 17 8 6 7 3
Phe 10 11 6 23 8 7 10 7
Tyr 9 8 10 18 5 8 9 6
Trp 5 6 1 7 2 1 4 5
Ser 42 31 33 45 77 58 27 35
Thr 27 19 42 37 31 24 14 31
Cys 2 1 3 2 1 1 1 1
Asn 13 19 16 15 11 13 18 14
Gln 32 24 30 27 22 23 11 18
Asp 10 18 8 10 8 13 8 17
Glu 37 32 18 18 24 40 17 31
Lys 29 30 16 50 30 27 43 27
Arg 28 28 16 47 43 25 54 26
His 8 10 4 15 3 8 7 7
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CAPN2 1q41 ENSG00000162909 824 CAPN2 114230
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Capn2 1:H4 ENSMUSG00000026509 12334 MGI:88264