Summary for peptidase C02.001: calpain-1

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

 

Names
MEROPS Namecalpain-1
Other namesCa2+-activated neutral protease, CAPN1 g.p. (Homo sapiens), calpain I, micro-calpain, mu-calpain
Domain architecture
MEROPS Classification
Classification Clan CA >> Subclan (none) >> Family C2 >> Subfamily A >> C02.001
Holotypecalpain-1 (Homo sapiens), Uniprot accession P07384 (peptidase unit: 85-337), MERNUM MER0000770
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00077
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.52
EnzymologyBRENDA database
Proteolytic eventsCutDB database (42 cleavages)
Activity statushuman: active (Sorimachi, 2004)
mouse: active (Azam et al., 2001)
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).
Mice in which the mu-calpain gene was specifically disrupted were viable and fertile, but abnormalities in platelet function were detected (Azam et al., 2001).
Pharmaceutical relevanceA drug target for stroke and neural injuries (Huang & Wang, 2001).
Pathways KEGGAlzheimer's disease
KEGGApoptosis
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Calpain-1
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/-Scissile bond-/-/-/- (based on 422 cleavages)
weblogo
Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 26 35 14 27 28 34 15 37
Pro 39 40 13 5 15 36 63 57
Ala 37 37 21 28 68 44 32 28
Val 14 31 40 11 26 25 23 18
Leu 32 32 99 16 38 23 22 20
Ile 7 12 15 4 8 20 13 13
Met 10 7 8 13 6 8 10 4
Phe 8 8 10 29 10 9 7 9
Tyr 5 6 10 24 3 3 7 8
Trp 5 10 3 9 3 3 8 3
Ser 46 31 45 44 60 45 26 30
Thr 24 19 33 36 27 22 23 28
Cys 1 1 2 3 1 1 3 2
Asn 14 10 15 17 9 15 18 14
Gln 22 21 24 24 21 29 18 20
Asp 10 7 13 9 5 8 6 12
Glu 30 31 14 23 13 36 7 20
Lys 27 38 16 47 33 27 42 27
Arg 25 21 13 37 40 17 48 22
His 10 8 4 15 6 6 7 9
Specificity from combinatorial peptides
 
Organism comment P4 P3 P2 P1 P1' P2' P3' P4' optimal substrate fluorophore or acceptor-donor pair Reference
Homo sapiens recombinant - P I/L F/Y - - - - xPIF+xxxx FAM-TAMRA Thomas et al., 2006
Rattus norvegicus recombinant F F L L/F M M/E R - FFLL+MMRx Edans-Dabcyl Cuerrier et al., 2005
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CAPN1 11q13.1 ENSG00000014216 823 CAPN1 114220
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Capn1 19:A ENSMUSG00000024942 12333 MGI:88263