Calpain small subunit 1 (CAPNS1)
The protein contains 268 amino acids for an estimated molecular weight of 28316 Da.
Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs17878750 |
The reference OMIM entry for this protein is 114170
Calpain, small subunit 1; capns1
Calpain 4; capn4
Canps
Calcium-dependent protease, small subunit; cdps
DESCRIPTION
Calcium-dependent cysteine proteinases, or calpains (EC 3.4.22.17), are widely distributed in mammalian cells. There are 2 distinct molecular forms, calpains I and II, which differ in the quantity of calcium required. Both calpains I and II are heterodimeric; each is composed of 1 heavy (about 80 kD), CAPN1 (114220) and CAPN2 (114230), respectively, and 1 shared light (about 30 kD) subunit, CAPNS1. The heavy subunit has a catalytic function, and the light subunit is regulatory.CLONING
Ohno et al. (1986) gave the nucleotide sequence for a nearly full-length cDNA coding for the small subunit of human calcium-dependent protease. A human spleen cDNA library was the source. The human protein has 268 amino acids.GENE FUNCTION
Using cell biologic, pharmacologic, and genetic methods, Chandramohanadas et al. (2009) found that the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii, the causative agents of malaria and toxoplasmosis, respectively, used host cell calpains to facilitate parasite egress. Immunodepletion and inhibition experiments showed that calpain-1 was required for escape of P. falciparum from human erythrocytes. Similarly, elimination of both calpain-1 and calpain-2 via small interfering RNA against the common regulatory subunit CAPNS1 in human osteosarcoma cells or deletion of Capns1 in mouse embryonic fibroblasts blocked egress of T. gondii. Chandramohanadas et al. (2009) concluded that P. falciparum and T. gondii both exploit host cell calpains to facilitate escape from intracellular parasitophorous vacuoles and/or the host plasma membrane, a process required for parasite proliferation.BIOCHEMICAL FEATURES
- Crystal Structure Blanchard et al. (1997) reported the crystal structure of the Ca(2+)-binding domain (domain VI) of rat Capns1 at 2.3-angstrom resolution, both with and without bound Ca(2+). Monomers of domain VI formed dimers with or without Ca(2+). The domain VI monomer was compact, predominantly alpha helical, and incorporated 5 EF-hand supersecondary structural elements. Only EF1, EF2, and EF3 were able to bind Ca(2+) at physiologic Ca(2+) concentrations, and EF1 showed a novel Ca(2+) coordination pattern.MAPPING
By a combination of spot blot hybridization with sorted chromosomes and of Southern hybridization with human-mouse cell hybrid DNAs, using in each case a cDNA probe, Ohno et al. (1990) assigned the CANPS gene to chromosome 19.ANIMAL MODEL
Using targeted disruption of the mouse Capn4 gene and casein zymography analysis, Arthur et al. (2000) demonstrated that wildtype and heterozygote embryonic stem cell lysates maintained mu- and m-calpain (i.e., calpain I and II) activities, whereas mutant homozygote embryonic stem cell lysates did not. Immunoblot analysis showed that the m-calpain large subunit was lost in Capn4 -/- cells. Growth of fibroblasts from day 9.5 Capn4 -/- embryos was indistinguishable from those of wildtype and heterozygous mice. At day 10.5, Capn4 -/- mice had a normal cardiovascular system except for apparent defects in the development of heart chambers and the vessels leading to and from the heart. After day 11.5, the accumulation of nucleated erythroid cells correlated with the death of all Capn4 -/- embryos. Although unable to determine a physiologic function for calpain, Arthur et al. (2000) concluded that calpain is essential for life. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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 16, 2016: Protein entry updated
Automatic update: OMIM entry 114170 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed