The Function of 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.
Protein names
Recommended name:
Calcium/calmodulin-dependent protein kinase type II subunit deltaAlternative name(s):
CaM kinase II subunit deltaCaMK-II subunit delta
- RS10023113 (CAMK2D) ??
- RS1880529 (CAMK2D) ??
- RS6858698 (CAMK2D) ??
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Top Gene-Substance Interactions
CAMK2D Interacts with These Diseases
| Disease | Score |
Substances That Increase CAMK2D
| Substances | Interaction | Organism | Category |
Substances That Decrease CAMK2D
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
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.
Gene Pathways:
Induction:
Activity is induced in skeletal muscle during exercise.
Enzyme Regulation:
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.
Molecular Function:
- Protein Serine/Threonine Kinase Activity
- Calmodulin-Dependent Protein Kinase Activity
- Ras Guanyl-Nucleotide Exchange Factor Activity
- Calmodulin Binding
- Atp Binding
- Sodium Channel Inhibitor Activity
- Titin Binding
- Protein Homodimerization Activity
- Ion Channel Binding
Biological Processes:
- G1/S Transition Of Mitotic Cell Cycle
- Mapk Cascade
- Regulation Of Cell Growth
- Response To Hypoxia
- Regulation Of The Force Of Heart Contraction
- Regulation Of Membrane Depolarization
- Regulation Of Transcription From Rna Polymerase Ii Promoter
- Protein Phosphorylation
- Calcium Ion Transport
- Regulation Of Heart Contraction
- Regulation Of G2/M Transition Of Mitotic Cell Cycle
- Positive Regulation Of Cardiac Muscle Hypertrophy
- Regulation Of Cell Communication By Electrical Coupling
- Positive Regulation Of Cardiac Muscle Cell Apoptotic Process
- Regulation Of Release Of Sequestered Calcium Ion Into Cytosol By Sarcoplasmic Reticulum
- Regulation Of Cardiac Muscle Contraction By Regulation Of The Release Of Sequestered Calcium Ion
- Positive Regulation Of Smooth Muscle Cell Migration
- Peptidyl-Serine Phosphorylation
- Peptidyl-Threonine Phosphorylation
- Cellular Potassium Ion Homeostasis
- Endoplasmic Reticulum Calcium Ion Homeostasis
- Positive Regulation Of Rac Protein Signal Transduction
- Protein Autophosphorylation
- Positive Regulation Of Smooth Muscle Cell Proliferation
- Protein Oligomerization
- Relaxation Of Cardiac Muscle
- Regulation Of Ryanodine-Sensitive Calcium-Release Channel Activity
- Interferon-Gamma-Mediated Signaling Pathway
- Regulation Of Cellular Localization
- Cell Growth Involved In Cardiac Muscle Cell Development
- Positive Regulation Of Erk1 And Erk2 Cascade
- Cellular Response To Calcium Ion
- Cardiac Muscle Cell Contraction
- Regulation Of Heart Rate By Cardiac Conduction
- Regulation Of Cardiac Muscle Cell Action Potential
- Regulation Of Cardiac Muscle Cell Action Potential Involved In Regulation Of Contraction
- Regulation Of Cellular Response To Heat
- Regulation Of Histone Deacetylase Activity
- Regulation Of Cell Communication By Electrical Coupling Involved In Cardiac Conduction
- Regulation Of Relaxation Of Cardiac Muscle
- Negative Regulation Of Sodium Ion Transmembrane Transport
- Regulation Of Calcium Ion Transmembrane Transport Via High Voltage-Gated Calcium Channel
- Negative Regulation Of Sodium Ion Transmembrane Transporter Activity