$VAR1 = undef;

Summary for peptidase C02.001: calpain-1

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Substrates Pharma

Names
MEROPS Name	calpain-1
Other names	Ca2+-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
Holotype	calpain-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 type	Cysteine
Peplist	Included in the Peplist with identifier PL00077
NC-IUBMB	Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.52
Enzymology	BRENDA database
Proteolytic events	CutDB database (42 cleavages)
Activity status	human: active (Sorimachi, 2004) mouse: active (Azam et al., 2001)
Physiology	Calcium-dependent degradation of cytoskeletal proteins in mammalian cytosol. Implicated in anoxic neuronal cell death in stroke and spinal injuries.
Knockout	In 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 relevance	A drug target for stroke and neural injuries (Huang & Wang, 2001).
Pathways	KEGG	Alzheimer's disease
	KEGG	Apoptosis
Other databases	WIKIPEDIA	http://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	-/-/-/--/-/-/- (based on 431 cleavages)

Specificity matrix

Amino acid	P4	P3	P2	P1	P1'	P2'	P3'	P4'
Gly	27	35	14	29	29	36	17	38
Pro	39	40	13	5	15	37	66	58
Ala	37	39	21	28	68	45	32	28
Val	14	31	41	11	26	25	23	20
Leu	32	32	102	16	40	24	22	20
Ile	8	12	17	4	8	21	13	13
Met	10	7	9	14	7	8	10	4
Phe	8	8	10	30	10	9	7	9
Tyr	6	6	10	24	3	3	7	8
Trp	5	10	3	9	3	3	8	3
Ser	48	32	45	45	62	45	27	31
Thr	24	19	34	36	29	22	23	28
Cys	1	1	3	3	1	1	3	2
Asn	14	10	15	17	10	15	18	15
Gln	23	22	24	25	21	30	18	21
Asp	10	7	13	10	5	8	6	12
Glu	31	32	14	23	13	38	7	20
Lys	27	40	16	47	33	27	42	27
Arg	26	23	13	39	40	17	49	22
His	11	8	4	15	6	6	8	10

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	-	-	-	-	xPIFxxxx	FAM-TAMRA	Thomas et al., 2006
Rattus norvegicus	recombinant	F	F	L	L/F	M	M/E	R	-	FFLLMMRx	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