CAMK2D a protein kinase of the calcium/calmodulin-dependent protein kinase (CAMK) group that interacts with the sarcoplasmic reticulum membrane in cardiac and skeletal muscle. Regulates Ca2+ homeostatis and excitation-contraction coupling (ECC) in heart. Calmodulin binding induces conformational changes that relieve autoinhibition, permitting autophosphorylation at T287, rendering the kinase constitutively active and independent of Ca2+-binding. Targets 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. Also targets 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 S2808. 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 SCN5A and the K+ channel Kv4.3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLB), an endogenous inhibitor of SERCA2A, 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 PLB and TRDN, a ryanodine receptor-coupling factor. CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with RRAD and CACNB2. Ten isoforms of the human protein are produced by alternative splicing. Isoform Delta3, isoform Delta2, isoform Delta8 and isoform Delta9 are expressed in cardiac muscle. Isoform Delta11 is expressed in skeletal muscle. Activity is induced in skeletal muscle during exercise. The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization. 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: 3|3 G1
Cellular Component:  axon initial segment; cytoplasm; cytosol; intercalated disc; membrane; neuromuscular junction; neuron projection; neuronal cell body; nucleus; perinuclear region of cytoplasm; plasma membrane; protein-containing complex; sarcoplasmic reticulum; T-tubule
Molecular Function:  ATP binding; calmodulin binding; calmodulin-dependent protein kinase activity; identical protein binding; ion channel binding; kinase activity; nitric-oxide synthase binding; nucleotide binding; protein binding; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activity; sodium channel inhibitor activity; titin binding; transferase activity
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; 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 cell communication by electrical coupling; 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 #:  Q6PHZ2 (UniProtKB)
Alt. Names/Synonyms: 2810011D23Rik; 8030469K03Rik; [d]-CaMKII; calcium/calmodulin-dependent protein kinase II, delta; Calcium/calmodulin-dependent protein kinase type II subunit delta; CaM kinase II subunit delta; CaMK II; CaMK-II subunit delta; Camk2d; KCC2D; Kiaa4163; MGC60852; mKIAA4163; OTTMUSP00000027703; OTTMUSP00000027705
Gene Symbols: Camk2d
Molecular weight: 56,369 Da
Basal Isoelectric point: 6.81  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
Select Structure to View Below


Protein Structure Not Found.

Substrate Sequence Logo
Open Substrate Page

Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene