CAMK , also written as CaMK or CCaMK , is an abbreviation for the Ca/calmodulin-dependent protein kinase class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca) and calmodulin . When activated, the enzymes transfer phosphates from ATP to defined serine or threonine residues in other proteins, so they are serine/threonine-specific protein kinases . Activated CAMK is involved in the phosphorylation of transcription factors and therefore, in the regulation of expression of responding genes. CAMK also works to regulate the cell life cycle (i.e. programmed cell death), rearrangement of the cell's cytoskeletal network, and mechanisms involved in the learning and memory of an organism.
7-445: There are 2 common types of CAM Kinase proteins: specialized and multi-functional CAM kinases. Once calcium concentrations in the cell rise, CAM kinases become saturated and bind the maximum of four calcium molecules. This calcium saturation activates the kinase and allows it to undergo a conformational change which permits the kinase to bind to its phosphorylation target sites. CAMK removes a phosphate group from ATP, most typically using
14-479: A Mg ion, and adds it to the CAM protein, rendering it active. The CAM Kinase contains a highly concentrated glycine loop where the gamma phosphate from the donor ATP molecule is easily able to bind to the enzyme which then utilizes the metal ion to facilitate a smooth phosphate transfer to the target protein. This phosphate transfer then activates the kinase's target and completes the phosphorylation cycle. Figure 1 shows how
21-548: A regulatory domain, an association domain, and a calcium/calmodulin binding domain. Members of the CAMK enzyme class include, but are not limited to: Pseudokinases are pseudoenzymes , proteins that resemble enzymes structurally, but lack catalytic activity. Some of these pseudokinases that are related to the CAMK family include: Pseudokinase Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across
28-430: A wide variety of diseases, which has made them potential drug targets and antitargets ). Pseudokinases are made up of an evolutionary mixture of eukaryotic protein kinase (ePK) and non ePK-related pseudoenzyme proteins (e.g., FAM20A , which binds ATP and is pseudokinase due to a conserved glutamate to glutamine swap in the alpha-C helix. FAM20A is implicated in periodontal disease , and serves to control
35-550: The catalytic activity of FAM20C , an important physiological casein kinase that controls phosphorylation of proteins in the Golgi apparatus that are destined for secretion, such as the milk protein casein . A comprehensive evolutionary analysis confirms that pseudokinases group into multiple subfamilies, and these are found in the annotated kinome of organisms across the kingdoms of life, including prokaryotes, archaea and all eukaryotic lineages with an annotated proteome ; this data
42-622: The kingdoms of life. Pseudokinases have both physiological ( signal transduction ) and pathophysiological functions. The phrase pseudokinase was first coined in 2002. They were subsequently sub-classified into different 'classes'. Several pseudokinase-containing families are found in the human kinome , including the Tribbles pseudokinases, which are at the interface between kinase and ubiquitin E3 ligase signalling. The human pseudokinases (and their pseudophosphatase cousins) are implicated in
49-412: The presence of calcium or calmodulin allows for the activation of CAM kinases (CAMK II). All kinases have a common structure of a catalytic core including an ATP binding site along with a larger substrate binding site. The catalytic core is typically composed of β-strands with the substrate binding site composed of α-helices. Most all CAM kinases includes a variety of domains, including: a catalytic domain,
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