Application | Comment | Organism |
---|---|---|
medicine | CaMKII inhibition may be a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
autocamide-2-related inhibitory peptide | i.e. AIP, used in its myristoylated form | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
sarcoplasmic reticulum | - |
Homo sapiens | 16529 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Ca2+ | required | Homo sapiens | |
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + ryanodine receptor type 2 | Homo sapiens | i.e. RyR2 | ADP + phosphorylated ryanodine receptor type 2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
heart | Left ventricular myocardial tissue | Homo sapiens | - |
myocardium | - |
Homo sapiens | - |
myocyte | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + ryanodine receptor type 2 | i.e. RyR2 | Homo sapiens | ADP + phosphorylated ryanodine receptor type 2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Ca2+/calmodulin-dependent protein kinase II | - |
Homo sapiens |
CaMKII | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at room temperature | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens | |
Calmodulin | required | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
metabolism | in human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca2+ leak. In the transition from hypertrophy to heart failure, the diastolic Ca2+ leak increases and disturbed Ca2+ cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. PKA-dependent RyR2 phosphorylation is not increased in heart failure and is independent of previous beta-blocker treatment. In heart failure, CaMKII inhibition but not inhibition of PKA yields a reduction of the SR Ca2+ leak. PKA inhibition further reduced SR Ca2+ load and systolic Ca2+ transients. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction | Homo sapiens |
physiological function | In hypertrophy, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA) both phosphorylated RyR2 at levels that were not different from healthy myocardium. In heart failure, the sarcoplasmic reticulum Ca2+ leak is nearly doubled compared with hypertrophy, which leads to reduced systolic Ca2+ transients, a depletion of sarcoplasmic reticulum Ca2+ storage and elevated diastolic Ca2+ levels. This is accompanied by a significantly increased CaMKII-dependent phosphorylation of RyR2. In heart failure, CaMKII inhibition but not inhibition of PKA yields a reduction of the sarcoplasmic reticulum Ca2+ leak | Homo sapiens |