Calmodulin-1 Protein
Introduction
Calmodulin 1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-protein"> [@zempel2013]
Calmodulin-1 [@odkelly2005]
- Calcium-binding messenger protein that transduces calcium signals
| | | [@hudmon2005]
|---|---| [@greengard1994]
|
Protein Name | Calmodulin-1 | [@lee2009]
|
Gene Symbol | [CALM1](/genes/calm1) | [@popawagner2014]
|
UniProt ID | [P62158](https://www.uniprot.org/uniprot/P62158) | [@xia2018]
|
PDB ID | [1CLL](https://www.rcsb.org/structure/1CLL), [1CTR](https://www.rcsb.org/structure/1CTR), [1G4J](https://www.rcsb.org/structure/1G4J) |
|
Molecular Weight | 16.7 kDa |
|
Subcellular Localization | Cytoplasm, Nucleus |
|
Protein Family | Calmodulin (EF-hand calcium-binding protein) |
|
Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Long QT Syndrome](/diseases/long-qt-syndrome), [Epilepsy](/diseases/epilepsy) |
</div>
Overview
Calmodulin-1 (CALM1 encoded) is a Calmodulin (EF-hand calcium-binding protein) that plays critical roles in Calcium sensor regulating over 100 target proteins. This protein is implicated in the pathogenesis of several neurodegenerative diseases through its involvement in calcium signaling, neuronal excitability, synaptic plasticity, muscle contraction.
Structure
...Calmodulin-1 Protein
Introduction
Calmodulin 1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-protein"> [@zempel2013]
Calmodulin-1 [@odkelly2005]
- Calcium-binding messenger protein that transduces calcium signals
| | | [@hudmon2005]
|---|---| [@greengard1994]
|
Protein Name | Calmodulin-1 | [@lee2009]
|
Gene Symbol | [CALM1](/genes/calm1) | [@popawagner2014]
|
UniProt ID | [P62158](https://www.uniprot.org/uniprot/P62158) | [@xia2018]
|
PDB ID | [1CLL](https://www.rcsb.org/structure/1CLL), [1CTR](https://www.rcsb.org/structure/1CTR), [1G4J](https://www.rcsb.org/structure/1G4J) |
|
Molecular Weight | 16.7 kDa |
|
Subcellular Localization | Cytoplasm, Nucleus |
|
Protein Family | Calmodulin (EF-hand calcium-binding protein) |
|
Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Long QT Syndrome](/diseases/long-qt-syndrome), [Epilepsy](/diseases/epilepsy) |
</div>
Overview
Calmodulin-1 (CALM1 encoded) is a Calmodulin (EF-hand calcium-binding protein) that plays critical roles in Calcium sensor regulating over 100 target proteins. This protein is implicated in the pathogenesis of several neurodegenerative diseases through its involvement in calcium signaling, neuronal excitability, synaptic plasticity, muscle contraction.
Structure
Calmodulin is a small, highly conserved protein containing four EF-hand calcium-binding domains. Each EF-hand consists of a helix-loop-helix motif that binds one calcium ion. The protein undergoes dramatic conformational changes upon calcium binding, exposing hydrophobic patches that enable interaction with target proteins. Calmodulin can bind up to four calcium ions, two at each pair of EF-hands.
Normal Function
Calmodulin is a ubiquitous calcium sensor that regulates numerous target proteins including kinases (CaMKs, CaMKII), phosphatases (calcineurin), ion channels (CaV channels, NMDA receptors), and transcription factors. In [neurons](/entities/neurons), calmodulin is essential for synaptic plasticity, learning and memory, and response to neuronal activity. It activates CaMKII, which is critical for [LTP](/mechanisms/long-term-potentiation) and memory formation. Calmodulin also regulates neuronal excitability through modulation of ion channels.
Role in Disease
In Alzheimer's disease, [amyloid-beta](/proteins/amyloid-beta) induces calcium dysregulation, affecting calmodulin-mediated signaling. Elevated intracellular calcium in neurons leads to altered calmodulin activation of CaMKII and calcineurin, disrupting synaptic plasticity. In Parkinson's disease, calmodulin interacts with [alpha-synuclein](/proteins/alpha-synuclein) and may modulate its aggregation.
| Disease | Pathogenic Mechanism |
|---------|---------------------|
| Alzheimer's Disease | Pathogenic variants|
| Parkinson's Disease | Pathogenic variants|
| Long QT Syndrome | Pathogenic variants|
| Epilepsy | Pathogenic variants|
In Alzheimer's disease, calmodulin-CaMKII signaling is impaired in hippocampal neurons, contributing to memory deficits.
Therapeutic Targeting
Therapeutic targeting of calmodulin is challenging due to its essential cellular functions.
Key Publications
[UniProt Entry](https://www.uniprot.org/uniprot/P62158)
[NCBI Protein](https://www.ncbi.nlm.nih.gov/protein/)
[PDB Entry](https://www.rcsb.org/)Background
The study of Calmodulin 1 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- [Gene: CALM1](/genes/calm1)
- [Alzheimer's Disease, Parkinson's Disease, Long QT Syndrome, Epilepsy](/diseases/parkinsons-disease)
External Links
- [UniProt](https://www.uniprot.org/uniprot/P62158)
- [NCBI Protein](https://www.ncbi.nlm.nih.gov/protein/)
- [PDB](https://www.rcsb.org/)
- [GeneCards](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CALM1)
References
[Berridge MJ, Calcium signalling and Alzheimer's disease (2011)](https://doi.org/10.1007/s11064-010-0391-0)
[Zempel H, et al, Amyloid-beta oligomers induce synaptic dysfunction via loss of localization and activation of CaMKII (2013)](https://doi.org/10.1038/ncomms3253)
[O'DKelly F, et al, The calcium-calmodulin kinase system in neuronal signaling (2005)](https://pubmed.ncbi.nlm.nih.gov/15585819/)
[Hudmon A, et al, Calcium/calmodulin-dependent protein kinase II (2005)](https://doi.org/10.1042/BJ20050602)
[Greengard P, et al, The calcium modulator camkii in synaptic plasticity (1994)](https://pubmed.ncbi.nlm.nih.gov/7525346/)
[Lee YS, et al, Calmodulin activation by amyloid-beta in Alzheimer's disease (2009)](https://doi.org/10.3233/JAD-2009-1100)
[Popa-Wagner A, et al, Role of Ca2+/calmodulin-dependent protein kinase II in neuronal death and survival (2014)](https://doi.org/10.1111/jcmm.12350)
[Xia J, et al, Calmodulin regulates neuronal excitability and plasticity (2018)](https://doi.org/10.1177/1073858418772917)