$VAR1 = undef;

Summary for peptidase C02.002: calpain-2

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

Names
MEROPS Name	calpain-2
Other names	Ca2+-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
Holotype	calpain-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 type	Cysteine
Peplist	Included in the Peplist with identifier PL00078
NC-IUBMB	Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.53
Enzymology	BRENDA database
Proteolytic events	CutDB database (112 cleavages)
Activity status	human: active (Sorimachi, 2004) mouse: active (Azuma et al., 2003)
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). 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 relevance	A 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	KEGG	Alzheimer's disease
	KEGG	Apoptosis
	KEGG	Focal adhesion
Other databases	WIKIPEDIA	http://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/--/-/-/- (based on 453 cleavages)

Specificity matrix

Amino acid	P4	P3	P2	P1	P1'	P2'	P3'	P4'
Gly	17	34	12	37	29	33	16	35
Pro	42	45	11	8	19	42	88	67
Ala	46	33	13	33	67	42	38	34
Val	25	31	49	12	24	21	29	21
Leu	29	37	124	25	31	36	23	25
Ile	8	10	26	5	7	18	10	11
Met	7	9	6	16	8	6	8	3
Phe	10	11	6	23	8	7	10	7
Tyr	10	8	10	18	5	8	9	6
Trp	5	6	1	7	2	1	4	5
Ser	42	31	33	45	76	58	27	36
Thr	27	19	42	37	32	24	14	31
Cys	2	1	3	2	1	1	1	1
Asn	13	19	16	15	11	13	18	14
Gln	32	25	30	27	22	23	11	18
Asp	10	18	8	10	8	13	8	17
Glu	36	32	18	19	24	40	17	31
Lys	30	30	16	50	30	27	43	27
Arg	28	28	16	48	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