Search Results
Overview
| Uniprot ID | Q13557 |
|---|---|
| Protein Name | Calcium/calmodulin-dependent protein kinase type II subunit delta |
| Gene Name | CAMK2D |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 301 | FNARRKLKGAILTTM |
| 318 | TRNFSAAKSLLKKPD |
| 322 | SAAKSLLKKPDGVKE |
| 43 | TGQEYAAKIINTKKL |
Function
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 (PubMed:17179159). 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 (PubMed:16690701). 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. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Biological Process | GO:0048168 | regulation of neuronal synaptic plasticity |
| Cellular Component | GO:0005954 | calcium- and calmodulin-dependent protein kinase complex |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0030666 | endocytic vesicle membrane |
| Cellular Component | GO:0016020 | membrane |
| Cellular Component | GO:0043005 | neuron projection |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0014069 | postsynaptic density |
| Cellular Component | GO:0042383 | sarcolemma |
| Cellular Component | GO:0033017 | sarcoplasmic reticulum membrane |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:0004683 | calcium/calmodulin-dependent protein kinase activity |
| Molecular Function | GO:0005516 | calmodulin binding |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0042803 | protein homodimerization activity |
| Molecular Function | GO:0106310 | protein serine kinase activity |
| Molecular Function | GO:0004674 | protein serine/threonine kinase activity |
| Molecular Function | GO:0019871 | sodium channel inhibitor activity |
| Molecular Function | GO:0031432 | titin binding |
| Molecular Function | GO:0044325 | transmembrane transporter binding |
| Biological Process | GO:0086003 | cardiac muscle cell contraction |
| Biological Process | GO:0071277 | cellular response to calcium ion |
| Biological Process | GO:0032469 | endoplasmic reticulum calcium ion homeostasis |
| Biological Process | GO:0060291 | long-term synaptic potentiation |
| Biological Process | GO:1902306 | negative regulation of sodium ion transmembrane transport |
| Biological Process | GO:0010666 | positive regulation of cardiac muscle cell apoptotic process |
| Biological Process | GO:0010613 | positive regulation of cardiac muscle hypertrophy |
| Biological Process | GO:0006468 | protein phosphorylation |
| Biological Process | GO:1902514 | regulation of calcium ion transmembrane transport via high voltage-gated calcium channel |
| Biological Process | GO:0098901 | regulation of cardiac muscle cell action potential |
| Biological Process | GO:0098909 | regulation of cardiac muscle cell action potential involved in regulation of contraction |
| Biological Process | GO:0010881 | regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion |
| Biological Process | GO:0010649 | regulation of cell communication by electrical coupling |
| Biological Process | GO:1901844 | regulation of cell communication by electrical coupling involved in cardiac conduction |
| Biological Process | GO:0001558 | regulation of cell growth |
| Biological Process | GO:0060341 | regulation of cellular localization |
| Biological Process | GO:0008016 | regulation of heart contraction |
| Biological Process | GO:0086091 | regulation of heart rate by cardiac conduction |
| Biological Process | GO:0003254 | regulation of membrane depolarization |
| Biological Process | GO:1903076 | regulation of protein localization to plasma membrane |
| Biological Process | GO:1901897 | regulation of relaxation of cardiac muscle |
| Biological Process | GO:0010880 | regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum |
| Biological Process | GO:0060314 | regulation of ryanodine-sensitive calcium-release channel activity |
| Biological Process | GO:0002026 | regulation of the force of heart contraction |
| Biological Process | GO:0006357 | regulation of transcription by RNA polymerase II |
| Biological Process | GO:0055119 | relaxation of cardiac muscle |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.
[3] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.