CALM2 Human
Description
Molecular Structure and Function
CALM2 is a 16 kDa protein composed of 149 amino acids, with two calcium-binding EF-hand domains connected by a flexible α-helical linker . Each EF-hand domain coordinates two calcium ions, enabling conformational changes that regulate target proteins . Key structural and functional features include:
CALM2 modulates over 300 intracellular targets, including kinases (e.g., CaMKII), phosphatases, and transcription factors, facilitating responses to calcium fluxes .
Cardiac Arrhythmias
Pathogenic CALM2 mutations are associated with life-threatening cardiac disorders:
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Long QT Syndrome (LQTS): Mutations (e.g., D130G, F142L) disrupt calcium-dependent inactivation of cardiac ion channels, prolonging ventricular repolarization .
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Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT): Aberrant CALM2-Ca²⁺ binding destabilizes ryanodine receptor (RyR2) function, triggering lethal arrhythmias during stress .
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Sudden Infant Death Syndrome (SIDS): Rare variants (e.g., N98S) impair calcium signaling in infancy, often exonerating wrongful convictions in multiple infant death cases .
Cancer
CALM2 is overexpressed in multiple cancers, driving progression through:
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Hepatocellular Carcinoma (HCC): Silencing CALM2 via siRNA reduces proliferation (88% in Huh1 cells) and migration by downregulating E2F5, a transcription factor linked to metastasis .
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Gastric Cancer (GC): CALM2 promotes angiogenesis and metastasis via the JAK2/STAT3/HIF-1α/VEGFA axis, increasing M2 macrophage polarization and tumor growth in murine models .
HCC Mechanisms
| Parameter | Effect of CALM2 Knockdown |
|---|---|
| Cell Proliferation | Reduced by 50–88% (MTT assay) |
| Apoptosis | Increased sub-G1 population by 6–15% (flow cytometry) |
| Tumor Growth | Abolished in vivo (PLC/PRF5 xenografts) |
Gastric Cancer Pathways
CALM2 upregulation in GC correlates with poor prognosis. Overexpression activates JAK2/STAT3 signaling, increasing HIF-1α and VEGFA to stimulate angiogenesis .
Expression in Human Tissues and Cancers
Data from The Human Protein Atlas highlight CALM2 expression across malignancies:
| Cancer Type | RNA Level | Protein Level | Prognostic Association |
|---|---|---|---|
| Hepatocellular | High | Medium | Poor survival |
| Gastric | High | High | Metastasis risk |
| Breast | Medium | Low | Not significant |
Therapeutic Implications
Product Specs
Product Science Overview
Calmodulin-2 is composed of 149 amino acids and has a molecular weight of approximately 16 kDa . It can bind up to four Ca²⁺ ions, which induces a conformational change in the protein. This change allows calmodulin to interact with and regulate various target proteins, including protein kinases, phosphatases, ion channels, and receptors . The binding of Ca²⁺ to calmodulin is essential for its role in cellular signaling pathways, particularly those involved in the regulation of the cell cycle and cytokinesis .
Recombinant human calmodulin-2 is typically expressed in Escherichia coli (E. coli) and purified using conventional chromatography techniques . The recombinant protein is often produced without any tags to maintain its native structure and function. The purity of the recombinant calmodulin-2 is usually greater than 90%, as determined by SDS-PAGE .
Calmodulin-2 is involved in various cellular processes, including the regulation of enzyme activity, ion channel function, and signal transduction pathways. It plays a critical role in the centrosome cycle and progression through cytokinesis . Additionally, calmodulin-2 is a substrate for various protein tyrosine kinases and is expected to be phosphorylated at specific sites, such as Thr 44 by CaMK4 .
Recombinant human calmodulin-2 is widely used in research to study calcium signaling pathways and the regulation of target proteins. It is also utilized in various biochemical assays to investigate the interactions between calmodulin and its binding partners. The recombinant protein is valuable for understanding the molecular mechanisms underlying calcium-mediated cellular processes and for developing potential therapeutic interventions targeting calmodulin-regulated pathways.
