Calmodulin-2 (CALM2)
The protein contains 149 amino acids for an estimated molecular weight of 16838 Da.
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). (updated: Sept. 12, 2018)
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.
No binding partner found
Biological Process
Calcium-mediated signaling
Detection of calcium ion
G protein-coupled receptor signaling pathway
G2/M transition of mitotic cell cycle
Microtubule cytoskeleton organization
Negative regulation of peptidyl-threonine phosphorylation
Negative regulation of ryanodine-sensitive calcium-release channel activity
Obsolete positive regulation by host of symbiont cAMP-mediated signal transduction
Positive regulation of cyclic-nucleotide phosphodiesterase activity
Positive regulation of DNA binding
Positive regulation of peptidyl-threonine phosphorylation
Positive regulation of phosphoprotein phosphatase activity
Positive regulation of protein autophosphorylation
Positive regulation of protein dephosphorylation
Positive regulation of protein serine/threonine kinase activity
Positive regulation of ryanodine-sensitive calcium-release channel activity
Regulation of cardiac muscle contraction
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
Regulation of cell communication by electrical coupling involved in cardiac conduction
Regulation of cytokinesis
Regulation of heart rate
Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
Regulation of ryanodine-sensitive calcium-release channel activity
Response to calcium ion
Substantia nigra development
Cellular Component
Calcium channel complex
Catalytic complex
Centrosome
Cytoplasm
Myelin sheath
Nucleus
Obsolete cell
Plasma membrane
Protein-containing complex
Sarcomere
Spindle microtubule
Spindle pole
Vesicle
Voltage-gated potassium channel complex
Molecular Function
Adenylate cyclase activator activity
Adenylate cyclase binding
Calcium channel inhibitor activity
Calcium ion binding
Disordered domain specific binding
Enzyme regulator activity
Ion channel binding
N-terminal myristoylation domain binding
Protein domain specific binding
Protein kinase binding
Protein phosphatase activator activity
Protein serine/threonine kinase activator activity
Titin binding
The reference OMIM entry for this protein is 114182
Calmodulin 2; calm2
Phkd2
CLONING
Sen Gupta et al. (1987) first identified and cloned the second calmodulin gene. Fischer et al. (1988) noted that, although the CALM1 (114180), CALM2, and CALM3 (114183) proteins are identical, at the nucleotide level they share only about 80% identity within their coding regions, and they contain no significant homology within their noncoding regions. Using a sequence from CALM3 as probe, Toutenhoofd et al. (1998) cloned CALM2 from a small intestine mucosa cDNA library. Northern blot analysis revealed a major 1.4-kb transcript in all tissues tested, with highest expression in brain. High levels of expression were also found in heart, placenta, lung, liver, skeletal muscle, and kidney, with lowest levels found in pancreas.GENE STRUCTURE
Toutenhoofd et al. (1998) determined that the CALM2 gene contains 6 exons and spans more than 16 kb. Within the 5-prime flanking region, CALM2 contains a TATA-like sequence, a far upstream CCAAT box, several AP1 (165160)-, AP2 (see 107580)-, and CRE (see 123811)-binding sites, and a repeated AGGGA motif that is found in other CALM genes.MAPPING
McPherson et al. (1991) tentatively assigned the CALM2 gene to chromosome 10 by study of somatic cell hybrids. However, by PCR-based amplification of CALM2-specific sequences using DNA from human/hamster cell hybrids as template, Berchtold et al. (1993) found that the CALM2 gene is located on chromosome 2. They regionalized the gene to 2p21.3-p21.1 by in situ hybridization.MOLECULAR GENETICS
- Long QT Syndrome 15 In a Hispanic girl with markedly prolonged QTc intervals and multiple episodes of ventricular fibrillation (LQT15; 616249), Crotti et al. (2013) performed exome sequencing and identified a heterozygous de novo missense mutation in the CALM2 gene (D96V; 114182.0001). In 5 unrelated patients of varying ancestry with long QT syndrome, Makita et al. (2014) identified heterozygosity for 5 different de novo missense mutations in the CALM2 gene (114182.0002-114182.0006). Functional analysis demonstrated significant reductions in calcium-binding affinity with the variants compared to wildtype calmodulin. ... More on the omim web site
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 114182 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).