Human Gene CAMK2D (uc003ibl.2) Description and Page Index
Description: Homo sapiens calcium/calmodulin-dependent protein kinase II delta (CAMK2D), transcript variant 4, mRNA. RefSeq Summary (NM_172115): 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]. Transcript (Including UTRs) Position: hg19 chr4:114,378,344-114,683,083 Size: 304,740 Total Exon Count: 17 Strand: - Coding Region Position: hg19 chr4:114,378,487-114,682,224 Size: 303,738 Coding Exon Count: 17
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=184.108.40.206; 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;
Genetic Association Studies of Complex Diseases and Disorders
E-Selectin Andrew D Paterson et al. Arteriosclerosis, thrombosis, and vascular biology 2009, Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin., Arteriosclerosis, thrombosis, and vascular biology.
ABO is a major locus for serum soluble E-selectin levels. We excluded population stratification, fine-mapped the association to sub-A alleles, and also document association with additional variation in the ABO region.
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.
Pfam Domains: PF00069 - Protein kinase domain PF07714 - Protein tyrosine kinase PF08332 - Calcium/calmodulin dependent protein kinase II association domain PF13474 - SnoaL-like domain PF14534 - Domain of unknown function (DUF4440)
ModBase Predicted Comparative 3D Structure on Q13557
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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
AK025368 - Homo sapiens cDNA: FLJ21715 fis, clone COL10287, highly similar to AF071569 Homo sapiens multifunctional calcium/calmodulin-dependent protein kinase II delta2 isoform mRNA. AK294517 - Homo sapiens cDNA FLJ53470 complete cds, highly similar to Calcium/calmodulin-dependent protein kinase type II delta chain (EC 220.127.116.11). AK055642 - Homo sapiens cDNA FLJ31080 fis, clone HSYRA2001615, highly similar to Calcium/calmodulin-dependent protein kinase type II delta chain (EC 18.104.22.168). AF071569 - Homo sapiens multifunctional calcium/calmodulin-dependent protein kinase II delta2 isoform mRNA, complete cds. AB209288 - Homo sapiens mRNA for calcium/calmodulin-dependent protein kinase II delta isoform 1 variant protein. BC032784 - Homo sapiens calcium/calmodulin-dependent protein kinase II delta, mRNA (cDNA clone MGC:44911 IMAGE:5178265), complete cds. AY987011 - Homo sapiens calcium/calmodulin-dependent protein kinase II delta mRNA, complete cds, alternatively spliced. EU176241 - Synthetic construct Homo sapiens clone IMAGE:100006427; FLH182803.01X; RZPDo839H07250D calcium/calmodulin-dependent protein kinase (CaM kinase) II delta (CAMK2D) gene, encodes complete protein. KJ896536 - Synthetic construct Homo sapiens clone ccsbBroadEn_05930 CAMK2D gene, encodes complete protein. KJ905159 - Synthetic construct Homo sapiens clone ccsbBroadEn_14565 CAMK2D gene, encodes complete protein. DQ895255 - Synthetic construct Homo sapiens clone IMAGE:100009715; FLH182796.01L; RZPDo839C05139D calcium/calmodulin-dependent protein kinase (CaM kinase) II delta (CAMK2D) gene, encodes complete protein. AB384909 - Synthetic construct DNA, clone: pF1KB4158, Homo sapiens CAMK2D gene for calcium/calmodulin-dependent protein kinase type II delta chain, complete cds, without stop codon, in Flexi system. U50361 - Human calcium, calmodulin-dependent protein kinase II delta mRNA, partial cds. U73738 - Human calcium/calmodulin-dependent protein kinase II delta E mRNA, partial cds. EF139846 - Homo sapiens clone 1-4 calcium/calmodulin-dependent protein kinase II splice variant (CAMK2D) mRNA, partial sequence; alternatively spliced. BC022558 - Homo sapiens calcium/calmodulin-dependent protein kinase II delta, mRNA (cDNA clone IMAGE:4794502), partial cds. AJ252239 - Homo sapiens partial mRNA for calcium/calmodulin dependent protein kinase II delta (CaMK II delta gene). JD065186 - Sequence 46210 from Patent EP1572962. JD124637 - Sequence 105661 from Patent EP1572962. JD075743 - Sequence 56767 from Patent EP1572962. JD336951 - Sequence 317975 from Patent EP1572962. JD222570 - Sequence 203594 from Patent EP1572962. JD174177 - Sequence 155201 from Patent EP1572962. JD203962 - Sequence 184986 from Patent EP1572962. JD140763 - Sequence 121787 from Patent EP1572962. JD142252 - Sequence 123276 from Patent EP1572962. JD399317 - Sequence 380341 from Patent EP1572962. JD193180 - Sequence 174204 from Patent EP1572962.