In mammalian cells, calcium/calmodulin-dependent protein kinase (CAMK) is composed of four different chains: alpha, beta, gamma, and delta; the enzyme is involved in the regulation of Ca(2+) homeostasis and excitation-contraction coupling (ECC) in heart by targeting ion channels. In order to better understand the role of CAMK in human cardiac disorders, changes in expression of the orthologous fly gene, Dmel\CaMKII , have assessed for heart function. Loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\CaMKII.
UAS constructs of the human genes Hsap\CAMK2D, Hsap\CAMK2A and Hsap\CAMK2B have been introduced into flies, but have not been characterized in the context of this human disease model.
Homozygous loss-of-function mutations of Dmel\CaMKII are lethal. Introduction of a mutation in the calmodulin-binding domain (M308V) results in animals with impaired heart function and a longer circadian rhythm period. Feeding of a chemical inhibitor of CAMK to wild-type adult flies results in reduced spontaneous heart rate without changes of the arrhythmicity index. CaMKII overexpression results in increased spontaneous frequency, decreased frequency variability, and modified intracellular Ca(2+) dynamics. Multiple genetic and physical interactions have been described for Dmel\CaMKII; see below and in the CaMKII gene report.
[updated Nov. 2020 by FlyBase; FBrf0222196]
The term "arrhythmia" refers to any change from the normal sequence of electrical impulses in the heart, such as atrial fibrillation, bradycardia (slow heartbeat), tachycardia (rapid heart rate), conduction disorders, rhythm disorders, ventricular fibrillation, premature contractions. Arrhythmias may be completely harmless or life-threatening. (http://www.heart.org/HEARTORG/Conditions/Arrhythmia/AboutArrhythmia/About-Arrhythmia_UCM_002010_Article.jsp)
These genes belong to the calcium/calmodulin-dependent protein kinase subfamily. In mammalian cells, calcium/calmodulin-dependent protein kinase is composed of four different chains: alpha, beta, gamma, and delta. This enzyme is involved in the regulation of Ca(2+) homeostasis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. [Gene Cards, CAMK2D; 2020.02.13]
Many to one: 4 human to 1 Drosophila; the human genes are CAMK2D, CAMK2A, CAMK2B, and CAMK2G.
Many to one: 4 human to 1 Drosophila; the human genes are CAMK2D, CAMK2A, CAMK2B, and CAMK2G.
Many to one: 4 human to 1 Drosophila; the human genes are CAMK2D, CAMK2A, CAMK2B, and CAMK2G.
Many to one: 4 human to 1 Drosophila; the human genes are CAMK2D, CAMK2A, CAMK2B, and CAMK2G.
High-scoring ortholog of human CAMK2D, CAMK2A, CAMK2B, and CAMK2G (1 Drosophila to 4 human). Dmel\CaMKII shares 70% identity and 78-80% similarity with CAMK2D and CAMK2A; it shares 56-63% identity and 63-73% similarity with CAMK2B and CAMK2G.
