Calmodulin-1 (CALM1)
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). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endomplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335).', '(Microbial infection) Required for Legionella pneumophila SidJ glutamylase activity. (updated: April 7, 2021)
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.
(right-click above to access to more options from the contextual menu)
No binding partner found
Biological Process
Activation of adenylate cyclase activity
Autophagosome membrane docking
Calcium-mediated signaling
Chemical synaptic transmission
Detection of calcium ion
Establishment of protein localization to mitochondrial membrane
Fc-epsilon receptor signaling pathway
G protein-coupled receptor signaling pathway
G2/M transition of mitotic cell cycle
Glycogen catabolic process
Inositol phosphate metabolic process
MAPK cascade
Microtubule cytoskeleton organization
Mitochondrion-endoplasmic reticulum membrane tethering
Muscle contraction
Negative regulation of high voltage-gated calcium channel activity
Negative regulation of peptidyl-threonine phosphorylation
Negative regulation of ryanodine-sensitive calcium-release channel activity
Obsolete cofactor metabolic process
Obsolete positive regulation by host of symbiont cAMP-mediated signal transduction
Organelle localization by membrane tethering
Platelet degranulation
Positive regulation of cyclic-nucleotide phosphodiesterase activity
Positive regulation of DNA binding
Positive regulation of nitric-oxide synthase activity
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 cell action potential
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 high voltage-gated calcium channel activity
Regulation of nitric-oxide synthase activity
Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
Regulation of rhodopsin mediated signaling pathway
Regulation of ryanodine-sensitive calcium-release channel activity
Regulation of synaptic vesicle endocytosis
Regulation of synaptic vesicle exocytosis
Response to amphetamine
Response to calcium ion
Response to corticosterone
Substantia nigra development
Tetrahydrobiopterin metabolic process
Viral process
Wnt signaling pathway, calcium modulating pathway
Cellular Component
Calcium channel complex
Catalytic complex
Centrosome
Cytoplasm
Cytosol
Extracellular region
Growth cone
Mitochondrial membrane
Myelin sheath
Nucleoplasm
Nucleus
Obsolete cell
Plasma membrane
Protein-containing complex
Sarcomere
Spindle microtubule
Spindle pole
Synaptic vesicle membrane
Vesicle
Voltage-gated potassium channel complex
Molecular Function
Adenylate cyclase activator activity
Adenylate cyclase binding
Calcium channel inhibitor activity
Calcium ion binding
Calcium-dependent protein binding
Disordered domain specific binding
Enzyme regulator activity
Inositol-1,4,5-trisphosphate 3-kinase activity
Ion channel binding
Ligand-gated ion channel activity
N-terminal myristoylation domain binding
Nitric-oxide synthase binding
Nitric-oxide synthase regulator activity
Phosphatidylinositol 3-kinase binding
Protein domain specific binding
Protein kinase binding
Protein phosphatase activator activity
Protein serine/threonine kinase activator activity
Ras guanyl-nucleotide exchange factor activity
Titin binding
Type 3 metabotropic glutamate receptor binding
The reference OMIM entry for this protein is 114180
Calmodulin 1; calm1
Phosphorylase kinase, delta subunit; phkd
DESCRIPTION
Calmodulin is the archetype of the family of calcium-modulated proteins of which nearly 20 members have been found. They are identified by their occurrence in the cytosol or on membranes facing the cytosol and by a high affinity for calcium. Calmodulin contains 149 amino acids and has 4 calcium-binding domains. Its functions include roles in growth and the cell cycle as well as in signal transduction and the synthesis and release of neurotransmitters.CLONING
Until the studies of Sen Gupta et al. (1987), only 1 human calmodulin cDNA had been reported. These authors found evidence of a second actively transcribed calmodulin gene in man. Calmodulin is the delta subunit of phosphorylase kinase, which has 3 other types of subunits. Although only 1 form of calmodulin has been found in humans, 3 distinct human cDNAs have been isolated that encode the identical polypeptide (Koller et al., 1990; Pegues and Friedberg, 1990). The existence of 3 expressible genes for calmodulin may indicate that one is a housekeeping gene and that the additional copies are differentially regulated to modulate calmodulin function. Rhyner et al. (1994) detected expression of CALM1 in all human tissues tested, although at varying levels. They identified 2 different CALM1-related pseudogenes. Toutenhoofd et al. (1998) found that all 3 CALM genes were expressed in human teratocarcinoma cells. CALM1 was expressed as a major 1.7-kb transcript and a minor 4.1-kb transcript. CALM1 was at least 5-fold less actively transcribed than CALM3 (114183).BIOCHEMICAL FEATURES
To determine how calcium/calmodulin activates calcium/calmodulin-dependent protein kinase I (CAMK1; 604998), Chin et al. (1997) characterized CAMK1 activation by calmodulin mutants with substitutions at hydrophobic residues. They found that CAMK1 activity is dependent on met124 within the C-terminal domain of calmodulin as well as on N-terminal hydrophobic residues of calmodulin. Kretsinger et al. (1986) described the crystal structure of calmodulin to 3.6-angstrom resolution. Schumacher et al. (2001) determined the crystal structure of calmodulin bound to KCNN2 (605879). The calmodulin-binding domain forms an elongated dimer with a calmodulin molecule bound at each end; each calmodulin wraps around 3 alpha-helices, 2 from 1 calmodulin-binding domain subunit and 1 from the other. Edema factor, the exotoxin of the anthrax bacillus, is transported into host cells by an anthrax-derived transporter, protective antigen. Together with lethal factor (see 603060), edema factor contributes significantly to both cutaneous and systemic anthrax and is an adenylyl cyclase activated by CALM1. Drum et al. (2002) described the crystal structures of edema factor alone and edema factor with CALM1 and 3-prime-deoxy-ATP. On calmodulin binding, an edema factor helical domain of 15 kD undergoes a 15-angstrom translation and a 30-degree rotation away from the edema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation.GENE STRUCTURE
Rhyner et al. (1994) found that the CALM1 gene contains 6 exons spread over about 10 kb of genomic DNA. The exon-intron structure was identical to that of CALM3. A cluster of transcription-start sites was identified 200 bp upstream of the ATG translation-start codon, and several putative regulatory elements were found in the 5-prime flanking region, as well as in intron 1. A short CAG trinucleotide repeat region w ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 114180 was added.