calml 2

Calmodulin (CaM) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of Calmodulin. Once bound to Ca2+, Calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases. Calmodulin is a small, highly conserved protein that is 148 amino acids long. The protein has two approximately symmetrical globular domains each containing a pair of EF-hand motifs (the N- and C-domain) separated by a flexible linker region for a total of four Ca2+ binding sites. Calmodulin mediates many crucial processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. Calmodulin is expressed in many cell types and can have different subcellular locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes, but it is always found intracellularly.

Calmodulin 2, also known as CALM2, is a calmodulin. Calmodulin 2 mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). It is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Calmodulin 2 gene may be a genetic determinant of hip osteoarthritis (OA). OA is a degenerative disease characterized by gradual loss of articular cartilage and is a leading cause of disability in elderly populations. CALM2 was most abundantly expressed in articular chondrocytes and OA cartilage.

Calcium/calmodulin-dependent protein kinase II beta (CAMK2B) is a member of the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. CaMKII is an important player in prostate cancer cells ability to escape apoptosis under androgen ablation and facilitate the progression of prostate cancer cells to an androgen independent state. As a multifunctional protein kinase, the loss of activity may play a critical role in initiating the changes leading to ischemia-induced cell death. CaMKII are found to be important for the functions of immune cells. CaMKII can be activated by TLR ligands, and in turn promotes both myeloid differentiating factor 88 and Toll/IL-1 receptor domain-containing adaptor protein-inducing IFN-beta-dependent inflammatory responses by directly activating TAK1 and IRF3. CAMKII has four subunit isoforms (alpha, beta, gamma, delta). It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. The alpha- and beta-isoforms have narrow distributions restricted mainly to neuronal tissues, but the gamma- and delta-isoforms are ubiquitously expressed within neuronal and non-neuronal tissues. CAMK2B is important for controlling the direction of plasticity at the parallel fiber-Purkinje cell synapse. CaMK2 is involved in neuronal survival through the reorganization of the neuroarchitecture and that the regulation of this role is controlled at the level of gene expression. Because CaMK2B influences the expression of many neuroreceptors and influences neural outgrowth and pruning, its altered expression in the cerebral cortex in schizophrenia or depression may contribute to schizophrenia and depression.