CAMK2D Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis 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. 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 Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) 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 Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) 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 Ca(2+) 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 Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Expressed in cardiac muscle and skeletal muscle. Isoform Delta 3, isoform Delta 2, isoform Delta 8 and isoform Delta 9 are expressed in cardiac muscle. Isoform Delta 11 is expressed in skeletal muscle. 10 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: CAMK group; CAMK2 family; EC; Kinase, protein; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of Human Ortholog: 2q42
Cellular Component:  axon initial segment; cytoplasm; cytosol; intercalated disc; neuromuscular junction; neuron projection; neuronal cell body; nucleus; perinuclear region of cytoplasm; protein-containing complex; sarcolemma; sarcoplasmic reticulum; sarcoplasmic reticulum membrane; T-tubule
Molecular Function:  ATP binding; calmodulin binding; calmodulin-dependent protein kinase activity; identical protein binding; ion channel binding; nitric-oxide synthase binding; protein binding; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activity; sodium channel inhibitor activity; titin binding
Biological Process:  calcium ion transport; cardiac muscle cell contraction; cardiac muscle contraction; cell growth involved in cardiac muscle cell development; cellular potassium ion homeostasis; endoplasmic reticulum calcium ion homeostasis; G1/S transition of mitotic cell cycle; negative regulation of sodium ion transmembrane transport; negative regulation of sodium ion transmembrane transporter activity; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; positive regulation of cardiac muscle cell apoptotic process; positive regulation of cardiac muscle hypertrophy; positive regulation of DNA biosynthetic process; positive regulation of ERK1 and ERK2 cascade; positive regulation of G2/M transition of mitotic cell cycle; positive regulation of Rac protein signal transduction; positive regulation of smooth muscle cell migration; positive regulation of vascular smooth muscle cell proliferation; protein autophosphorylation; protein complex oligomerization; protein phosphorylation; regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; regulation of cardiac muscle cell action potential; regulation of cardiac muscle cell action potential involved in regulation of contraction; regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; regulation of cell communication by electrical coupling; regulation of cell communication by electrical coupling involved in cardiac conduction; regulation of cellular localization; regulation of membrane depolarization; regulation of protein localization to plasma membrane; regulation of relaxation of cardiac muscle; regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; regulation of sodium ion transport; relaxation of cardiac muscle; response to hypoxia
Reference #:  P15791 (UniProtKB)
Alt. Names/Synonyms: Ca++/calmodulin-dependent protein kinase 2 delta subunit; Ca++/calmodulin-dependent protein kinase II delta subunit; Ca++/calmodulin-dependent protein kinase II, delta subunit; calcium/calmodulin-dependent protein kinase (CaM kinase) II delta; calcium/calmodulin-dependent protein kinase II delta; calcium/calmodulin-dependent protein kinase type II delta chain; Calcium/calmodulin-dependent protein kinase type II subunit delta; CaM kinase II subunit delta; caM-kinase II delta chain; CaMK-II subunit delta; CAMK1; Camk2; Camk2d; Camki; KCC2D; MGC124639; RATCAMKI
Gene Symbols: Camk2d
Molecular weight: 60,081 Da
Basal Isoelectric point: 6.84  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  GPCR Signaling to MAPKs  |  Microtubule Dynamics  |  Mitochondrial Control of Apoptosis  |  Phospholipase Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene