Human Gene CAMK2D (ENST00000394524.7) from GENCODE V44
Description: Homo sapiens calcium/calmodulin dependent protein kinase II delta (CAMK2D), transcript variant 2, mRNA. (from RefSeq NM_172128) RefSeq Summary (NM_172128): The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns.[provided by RefSeq, Nov 2008]. Gencode Transcript: ENST00000394524.7 Gencode Gene: ENSG00000145349.20 Transcript (Including UTRs) Position: hg38 chr4:113,451,032-113,761,445 Size: 310,414 Total Exon Count: 18 Strand: - Coding Region Position: hg38 chr4:113,454,512-113,761,068 Size: 306,557 Coding Exon Count: 18
ID:KCC2D_HUMAN DESCRIPTION: RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit delta; Short=CaM kinase II subunit delta; Short=CaMK-II subunit delta; EC=2.7.11.17; 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. 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. 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. SUBUNIT: 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 (By similarity). SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Peripheral membrane protein; Cytoplasmic side (Probable). Sarcoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (Probable). 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. INDUCTION: Activity is induced in skeletal muscle during exercise. DOMAIN: The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization. PTM: Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state. MISCELLANEOUS: Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy in PubMed:10189359. SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=BAD92525.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13557
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000165 MAPK cascade GO:0001558 regulation of cell growth GO:0002026 regulation of the force of heart contraction GO:0003254 regulation of membrane depolarization GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006468 protein phosphorylation GO:0007399 nervous system development GO:0008016 regulation of heart contraction GO:0010613 positive regulation of cardiac muscle hypertrophy GO:0010649 regulation of cell communication by electrical coupling GO:0010666 positive regulation of cardiac muscle cell apoptotic process GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0030154 cell differentiation GO:0032469 endoplasmic reticulum calcium ion homeostasis GO:0046777 protein autophosphorylation GO:0051259 protein oligomerization GO:0055119 relaxation of cardiac muscle GO:0060314 regulation of ryanodine-sensitive calcium-release channel activity GO:0060333 interferon-gamma-mediated signaling pathway GO:0060341 regulation of cellular localization GO:0071277 cellular response to calcium ion GO:0086003 cardiac muscle cell contraction GO:0086091 regulation of heart rate by cardiac conduction GO:0098901 regulation of cardiac muscle cell action potential GO:0098909 regulation of cardiac muscle cell action potential involved in regulation of contraction GO:1901725 regulation of histone deacetylase activity GO:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction GO:1901897 regulation of relaxation of cardiac muscle GO:1902306 negative regulation of sodium ion transmembrane transport GO:1902514 regulation of calcium ion transmembrane transport via high voltage-gated calcium channel GO:2000650 negative regulation of sodium ion transmembrane transporter activity
US Server
