CaMPDB :: Calpain

CL0890 : calpain 2

* Basic Information

Organism	Homo sapiens (human)
Protein Names	large subunit; calpain; large polypeptide L2; calcium-activated neutral proteinase; Calpain 2; large [catalytic] subunit; calpain 2, large subunit [Homo sapiens]; Calpain-2 catalytic subunit; 3.4.22.53; Calpain-2 large subunit; Calcium-activated neutral proteinase 2; CANP 2; Calpain M-type; M-calpain; Millimolar-calpain; Calpain large polypeptide L2
Gene Names	CAPN2; CANPL2; calpain 2, (m/II) large subunit
Gene Locus	1q41-q42; chromosome 1
GO Function	GO:0004198 - calpain activity [Evidence IEA]; GO:0005509 - calcium ion binding [Evidence IEA]

Entrez Protein	Entrez Nucleotide	Entrez Gene	UniProt	OMIM	HGNC	HPRD	KEGG
NP_001739	NM_001748	824	P17655	114230	1479	N/A	hsa:824

* Information From OMIM

Description: The calpains, or calcium-activated neutral proteases (EC 3.4.22.17), are nonlysosomal intracellular cysteine proteases. The mammalian calpains include 2 ubiquitous proteins, CAPN1 (OMIM:114220) and CAPN2, 2 stomach-specific proteins, and CAPN3 (OMIM:114240), which is muscle-specific. The ubiquitous enzymes are heterodimers with distinct large subunits associated with a common small subunit (CAPNS1; OMIM:114170), all of which are encoded by different genes.

» More (4) « Hide Below

Function: By quantitative RT-PCR, Ueyama et al. (1998) found that expression of calpain-1 and calpain-2 mRNA was significantly increased in muscle biopsy samples derived from 5 men with progressive muscular dystrophy (e.g., DMD; OMIM:310200) and 2 men and 3 women with amyotrophic lateral sclerosis (ALS; OMIM:105400) compared with controls.

Function: Morford et al. (2002) found that calpain-2, but not calpain-1, associated with membrane lipid rafts on human peripheral blood T cells and Jurkat T cells. Membrane raft-associated calpain activity in human T cells was enhanced with exogenous calcium. Calpain cleaved the cytoskeletal-associated protein talin (TLN1; OMIM:186745) during the first 30 minutes after cell stimulation. Morford et al. (2002) hypothesized that lipid raft-associated calpain-2 could function early in T-cell receptor signaling to facilitate immune synapse formation through cytoskeletal remodeling mechanisms.

Function: Using confocal microscopy and isopycnic density centrifugation, Hood et al. (2003) found that calpain-1, calpain-2, the small regulatory calpain subunit, and calpastatin (CAST; OMIM:114090) associated with the endoplasmic reticulum and Golgi apparatus of human fibroblasts and glioblastoma cells. The association between these proteins and the endoplasmic reticulum and Golgi apparatus increased in the glioblastoma cell line following laminin (see LAMA1; OMIM:150320) stimulation. Calpain-2 also colocalized with inositol 4,5-bisphosphate and with membrane lipid rafts.

Function: Adamec et al. (2002) investigated calpain-2 activation in a broad range of neurodegenerative diseases using immunofluorescence imaging. Activated calpain-2 was detected in all neurodegenerative diseases examined, including Alzheimer disease (AD; OMIM:104300), Down syndrome (OMIM:190685), and Pick disease (OMIM:172700), with the possible exception of frontotemporal dementia with inclusions (see OMIM:600274). Activated calpain-2 was detected in different cell types and colocalized with different pathologic structures. In neurons and glial cells, calpain-2 primarily colocalized with hyperphosphorylated tau protein (MAPT; OMIM:157140). In brains with AD neurofibrillary changes, colocalization of calpain-2 with phosphorylated tau was most extensive at transentorhinal stages of neurofibrillary degeneration rather than at later limbic stages. Aggregates of different proteins, such as huntingtin (HD; OMIM:143100) and alpha-synuclein (SNCA; OMIM:163890), were negative for activated calpain-2, indicating that the presence of pathologic inclusions was not by itself the stimulus responsible for calpain-2 activation.

* Structure Information

1. Primary Information

Length: 700 aa

Average Mass: 80.006 kDa

Monoisotopic Mass: 79.956 kDa

2. Domain Information

Annotated Domains: interpro / pfam / smart / prosite

Computationally Assigned Domains (Pfam+HMMER):

domain name	begin	end	score	e-value
Peptidase_C2 1.	45	344	808.0	6.2e-240
Calpain_III 1.	355	510	393.6	3.4e-115
efhand 1.	576	604	20.4	0.0074
efhand 2.	606	634	19.4	0.015
efhand 3.	671	699	4.0	7.6

3. Sequence Information

Fasta Sequence: CL0890.fasta

Amino Acid Sequence and Secondary Structures (PsiPred):

4. 3D Information

Known Structures in PDB: 1KFU (X-ray; 250 A; L=1-700), 1KFX (X-ray; 315 A; L=1-700), 2NQA (X-ray; 220 A; A=43-346)

* References

[PubMed ID: 17359359] Medana IM, Day NP, Hien TT, Mai NT, Bethell D, Phu NH, Turner GD, Farrar J, White NJ, Esiri MM, Cerebral calpain in fatal falciparum malaria. Neuropathol Appl Neurobiol. 2007 Apr;33(2):179-92.

» More (10) « Hide Below

[PubMed ID: 17192410] ... Nuzzi PA, Senetar MA, Huttenlocher A, Asymmetric localization of calpain 2 during neutrophil chemotaxis. Mol Biol Cell. 2007 Mar;18(3):795-805. Epub 2006 Dec 27.

[PubMed ID: 16652152] ... Carragher NO, Walker SM, Scott Carragher LA, Harris F, Sawyer TK, Brunton VG, Ozanne BW, Frame MC, Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function. Oncogene. 2006 Sep 21;25(42):5726-40. Epub 2006 May 1.

[PubMed ID: 16816119] ... Su Y, Cui Z, Li Z, Block ER, Calpain-2 regulation of VEGF-mediated angiogenesis. FASEB J. 2006 Jul;20(9):1443-51.

[PubMed ID: 16598790] ... Courdier-Fruh I, Briguet A, Utrophin is a calpain substrate in muscle cells. Muscle Nerve. 2006 Jun;33(6):753-9.

[PubMed ID: 12665801] ... Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J, Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31.

[PubMed ID: 1527057] ... Adachi Y, Kitahara-Ozawa A, Sugamura K, Lee WJ, Yodoi J, Maki M, Murachi T, Hatanaka M, Expression of calpain II gene in human hematopoietic system cells infected with human T-cell leukemia virus type I. J Biol Chem. 1992 Sep 25;267(27):19373-8.

[PubMed ID: 2209092] ... Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K, Four genes for the calpain family locate on four distinct human chromosomes. Cytogenet Cell Genet. 1990;53(4):225-9.

[PubMed ID: 2539381] ... Hata A, Ohno S, Akita Y, Suzuki K, Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit of calcium-dependent protease. J Biol Chem. 1989 Apr 15;264(11):6404-11.

[PubMed ID: 2852952] ... Imajoh S, Aoki K, Ohno S, Emori Y, Kawasaki H, Sugihara H, Suzuki K, Molecular cloning of the cDNA for the large subunit of the high-Ca2+-requiring form of human Ca2+-activated neutral protease. Biochemistry. 1988 Oct 18;27(21):8122-8.

[PubMed ID: 1067155] ... Kopp S, Reproducibility of response to a questionnaire on symptoms of masticatory dysfunction. Community Dent Oral Epidemiol. 1976 Sep;4(5):205-9.