Calpain-2 catalytic subunit (CAPN2)

The protein contains 700 amino acids for an estimated molecular weight of 79995 Da.

 

Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226' (PubMed:17650508). Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs (By similarity). (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  4. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs25655
dbSNP:rs2230083
dbSNP:rs9804140
dbSNP:rs28370127
dbSNP:rs17599
dbSNP:rs2230082

The reference OMIM entry for this protein is 114230

Calpain 2; capn2
Calpain, large polypeptide l2
Calpain ii, large subunit; canpl2
Calcium-activated neutral protease 2, catalytic subunit; canp2

DESCRIPTION

The calpains, or calcium-activated neutral proteases (EC 3.4.22.17), are nonlysosomal intracellular cysteine proteases. The mammalian calpains include 2 ubiquitous isoforms, calpain I (mu-calpain) and calpain II (m-calpain), 2 stomach-specific proteins, and CAPN3 (114240), which is muscle-specific. Calpain I and calpain II are heterodimers with distinct large subunits, encoded by the CAPN1 (114220) and CAPN2 genes, respectively, associated with a common small subunit (CAPNS1; 114170).

CLONING

By screening a human skeletal muscle cDNA library using the large subunits of rabbit and chicken CANP as probes, Imajoh et al. (1988) cloned CAPN2. The deduced protein contains 700 amino acids. N-terminal sequencing of CAPN2 purified from human liver indicated that the N-terminal methionine is removed, resulting in a mature 699-amino acid subunit with a calculated molecular mass of 79.9 kD. Comparison of the CAPN2 sequence with CAPN1 and the chicken CANP large subunit showed conservation of the 4-domain structure and of the active-site cysteine (cys140) in the protease domain (domain II) and the 4 putative Ca(2+)-binding sites in domain IV. Domain III, presumably a regulatory domain, is also highly conserved between the 3 proteins, but domain I is not.

GENE 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; 310200) and 2 men and 3 women with amyotrophic lateral sclerosis (ALS; 105400) compared with controls. 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; 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. 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; 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; 150320) stimulation. Calpain-2 also colocalized with inositol 4,5-bisphosphate and with membrane lipid rafts. 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; 104300), Down syndrome (190685), and Pick disease (172700), with the possible exception of frontotemporal dementia with inclusions (see 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; 157140). In brains with AD neurofibrillary changes, colocalization of calpain-2 with phosphorylated tau was mos ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 26, 2017: Protein entry updated
Automatic update: model status changed

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CAPN2

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 114230 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed