CAMK2D

The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns

calcium/calmodulin-dependent protein kinase II delta

Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca2+ homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca2+ influx into the myocyte, Ca2+ release from the sarcoplasmic reticulum (SR), SR Ca2+ uptake and Na+ and K+ channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca2+ release via direct phosphorylation of RYR2 Ca2+ channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program. Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca2+ influx to myocytes by binding and phosphorylating the L-type Ca2+ channel subunit beta-2 CACNB2. In addition to Ca2+ channels, can target and regulate the cardiac sarcolemmal Na+ channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca2+ uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis. May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca2+ transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor.

Cardiac muscle cell contraction Source: BHF-UCL
Cellular response to calcium ion Source: BHF-UCL
Endoplasmic reticulum calcium ion homeostasis Source: BHF-UCL
Interferon-gamma-mediated signaling pathway Source: Reactome
Negative regulation of sodium ion transmembrane transport Source: BHF-UCL
Negative regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
Peptidyl-serine phosphorylation Source: BHF-UCL
Peptidyl-threonine phosphorylation Source: BHF-UCL
Positive regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
Positive regulation of cardiac muscle hypertrophy Source: UniProtKB
Protein autophosphorylation Source: BHF-UCL
Protein phosphorylation Source: UniProtKB
Regulation of calcium ion transmembrane transport via high voltage-gated calcium channel Source: BHF-UCL
Regulation of cardiac muscle cell action potential Source: BHF-UCL
Regulation of cardiac muscle cell action potential involved in regulation of contraction Source: BHF-UCL
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: UniProtKB
Regulation of cell communication by electrical coupling Source: BHF-UCL
Regulation of cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
Regulation of cell growth Source: UniProtKB
Regulation of cellular localization Source: UniProtKB
Regulation of cellular response to heat Source: Reactome
Regulation of heart contraction Source: UniProtKB
Regulation of heart rate by cardiac conduction Source: BHF-UCL
Regulation of histone deacetylase activity Source: BHF-UCL
Regulation of membrane depolarization Source: BHF-UCL
Regulation of relaxation of cardiac muscle Source: BHF-UCL
Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: BHF-UCL
Regulation of ryanodine-sensitive calcium-release channel activity Source: UniProtKB
Regulation of the force of heart contraction Source: BHF-UCL
Regulation of transcription by RNA polymerase II Source: BHF-UCL
Relaxation of cardiac muscle Source: BHF-UCL

Sarcolemma; Sarcoplasmic reticulum membrane

Autophosphorylation of Thr-287 following activation by Ca2+/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.