CAMK2D - Calcium/calmodulin-dependent protein kinase type II subunit delta - human protein (Function)
 
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CAMK2D »  Calcium/calmodulin-dependent protein kinase type II subunit delta   [ EC 2.7.11.17 ]  (CaMK-II subunit delta)
 
Gene name:  CAMK2D
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
3
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Calmodulin bindingdefinition[GO:0005516]  
1
  • BHF-UCL
Calmodulin-dependent protein kinase activitydefinition[GO:0004683]  
2
  • BHF-UCL
Ion channel bindingdefinition[GO:0044325]  
2
  • BHF-UCL
Nitric-oxide synthase bindingdefinition[GO:0050998] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
2
  • IntAct
Protein homodimerization activitydefinition[GO:0042803]  
1
  • BHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • BHF-UCL
Sodium channel inhibitor activitydefinition[GO:0019871]  
1
  • BHF-UCL
Titin bindingdefinition[GO:0031432]  
1
  • BHF-UCL
GO biological process 
Calcium ion transportdefinition[GO:0006816] silver  
1
  • Ortholog Compara
Cardiac muscle cell contractiondefinition[GO:0086003]  
1
  • BHF-UCL
Cell growth involved in cardiac muscle cell developmentdefinition[GO:0061049] silver  
1
  • Ortholog Compara
Cellular potassium ion homeostasisdefinition[GO:0030007] silver  
1
  • Ortholog Compara
Cellular response to calcium iondefinition[GO:0071277]  
1
  • BHF-UCL
Endoplasmic reticulum calcium ion homeostasisdefinition[GO:0032469]  
1
  • Ortholog Curator
G1/S transition of mitotic cell cycledefinition[GO:0000082] silver  
1
  • Ortholog Compara
Negative regulation of sodium ion transmembrane transportdefinition[GO:1902306]  
1
  • BHF-UCL
Negative regulation of sodium ion transmembrane transporter activitydefinition[GO:2000650]  
1
  • BHF-UCL
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
2
  • BHF-UCL
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
2
  • BHF-UCL
Positive regulation of cardiac muscle hypertrophydefinition[GO:0010613]  
1
  • UniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374] silver  
1
  • Ortholog Compara
Positive regulation of Rac protein signal transductiondefinition[GO:0035022] silver  
1
  • Ortholog Compara
Positive regulation of smooth muscle cell migrationdefinition[GO:0014911] silver  
1
  • Ortholog Compara
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661] silver  
1
  • Ortholog Compara
Protein autophosphorylationdefinition[GO:0046777]  
1
  • BHF-UCL
Protein oligomerizationdefinition[GO:0051259]  
1
  • BHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
2
  • BHF-UCL
  • UniProtKB
Regulation of cardiac muscle cell action potentialdefinition[GO:0098901]  
1
  • Ortholog Curator
Regulation of cardiac muscle cell action potential involved in regulation of contractiondefinition[GO:0098909]  
1
  • BHF-UCL
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium iondefinition[GO:0010881]  
2
  • UniProtKB
  • BHF-UCL
Regulation of cell communication by electrical couplingdefinition[GO:0010649]  
1
  • Ortholog Curator
Regulation of cell communication by electrical coupling involved in cardiac conductiondefinition[GO:1901844]  
1
  • BHF-UCL
Regulation of cell growthdefinition[GO:0001558]  
1
  • UniProtKB
Regulation of cellular localizationdefinition[GO:0060341]  
1
  • UniProtKB
Regulation of G2/M transition of mitotic cell cycledefinition[GO:0010389] silver  
1
  • Ortholog Compara
Regulation of generation of L-type calcium currentdefinition[GO:1902514]  
1
  • Ortholog Curator
Regulation of heart contractiondefinition[GO:0008016]  
1
  • UniProtKB
Regulation of heart rate by cardiac conductiondefinition[GO:0086091]  
1
  • BHF-UCL
Regulation of histone deacetylase activitydefinition[GO:1901725]  
1
  • BHF-UCL
Regulation of membrane depolarizationdefinition[GO:0003254]  
1
  • BHF-UCL
Regulation of relaxation of cardiac muscledefinition[GO:1901897]  
1
  • BHF-UCL
Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulumdefinition[GO:0010880]  
1
  • Ortholog Curator
Regulation of ryanodine-sensitive calcium-release channel activitydefinition[GO:0060314]  
2
  • UniProtKB
  • BHF-UCL
Regulation of the force of heart contractiondefinition[GO:0002026]  
1
  • BHF-UCL
Regulation of transcription from RNA polymerase II promoterdefinition[GO:0006357]  
1
  • BHF-UCL
Relaxation of cardiac muscledefinition[GO:0055119]  
1
  • BHF-UCL
Response to hypoxiadefinition[GO:0001666] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.17: ATP + a protein ADP + a phosphoprotein.  
1
  • UniProtKB
It is regulated in the following manner
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.  
2
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Calcium signaling pathway  hsa04020+817  
Cholinergic synapse  hsa04725+817  
Dopaminergic synapse  hsa04728+817  
ErbB signaling pathway  hsa04012+817  
Gastric acid secretion  hsa04971+817  
Glioma  hsa05214+817  
GnRH signaling pathway  hsa04912+817  
Long-term potentiation  hsa04720+817  
Melanogenesis  hsa04916+817  
Neurotrophin signaling pathway  hsa04722+817  
Olfactory transduction  hsa04740+817  
Oocyte meiosis  hsa04114+817  
Tuberculosis  hsa05152+817  
Wnt signaling pathway  hsa04310+817  
According to Reactome, this protein belongs to the following pathways:
CREB phosphorylation through the activation of CaMKII  REACT_20642  
CREB phosphorylation through the activation of Ras  REACT_20568  
HSF1-dependent transactivation  REACT_264164  
Interferon gamma signaling  REACT_25078  
Ras activation uopn Ca2+ infux through NMDA receptor  REACT_20546  
Trafficking of AMPA receptors  REACT_18307  
Unblocking of NMDA receptor, glutamate binding and activation  REACT_20594  
Note 
Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy in PubMed:10189359.  
1
  • UniProtKB
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: CAMK2D
GenomeRNAi: 817
PRO: PR:Q13557
Chemistry
GuidetoPHARMACOLOGY: 1558