Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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calcium/calmodulin dependent protein kinase II alpha(CAMK2A) calcium/calmodulin dependent protein kinase II alpha(CAMK2A) Related Genes Homo sapiens
CHROMOSOME 5,
CYTOBAND 5q33.1,
ENSEMBL_GENE_ID ENSG00000070808,
GENERIF_SUMMARY Four distinct isoforms of CAMKII were isolated. Two of them were characterized as CaMKII alpha and beta subunits.CaMKII expression is developmentally regulated in human fetal and adult brain, the NPY Y(1) receptor induces the expression of CRE containing target genes through the CaM kinase-CREB pathway, role in cell communication, CaMKII alpha mRNA expression is significantly reduced in the prefrontal cortex of patients with bipolar illness., Calcium/calmodulin-dependent protein kinase II binds to Raf-1 and modulates integrin-stimulated ERK activation, measured differences in CaMKII binding affinities for CaM play a minor role in the autophosphorylation of the enzyme, largely dictated by autophosphorylation rate for alpha, beta, gamma and delta isoforms, CaMKII-alpha may be related with beta-amyloid more closely than being involved in tau hyperphosphorylation in Alzheimer's disease, novel mechanism for Ca2+-dependent negative-feedback regulation of NR2B-containing NMDARs in a CaMKII activity- and autophosphorylation-dependent manner that may modulate NMDAR-mediated synaptic plasticity, activation of the IKK/NFkappaB signaling cascade by SSTR2 requires a complicated network consisting of Galpha(14), protein kinase C, CamkII, ERK, and c-Src, The expression of CaMKII alpha was significantly elevated in depression., The expression of CaMKIIalpha is significantly elevated in depression (29%), but not in schizophrenia or bipolar disorder, compared to healthy controls., EGF has the ability to abrogate the PP2A function in the maintenance of beta1 integrin-mediated cell adhesion by dissociation of PP2A-IQGAP1-CaMKII from beta1 integrin-Rac through activation of CaMKII, CD44 interaction with LARG and EGFR plays a pivotal role in Rho/Ras co-activation, PLC epsilon-Ca2+ signaling, and Raf/ERK up-regulation required for CaMKII-mediated cytoskeleton function and in head and neck squamous cell carcinoma progression, voltage-dependent facilitation of the Ca(v)1.2 channel depends on the phosphorylation of Ser1512/Ser1570 by calmodulin kinase II, To characterize the human alphaCaMKII promoter, a promoter-reporter gene assay using different cell lines, was developed., Amphetamine sensitization in rats, an animal model of schizophrenia, results in significant increase in CaMKII beta and a nonsignificant increase in CaMKII alpha mRNA., Skeletal muscle CaMKII kinase isoform expression and serum response factor phosphorylation is higher with endurance-type exercise training, adaptations that are restricted to active muscle., alpha-CaMKII controls the growth of human osteosarcoma by regulating cell cycle progression, These findings revealed that TNF-alpha induced VCAM-1 expression via multiple signaling pathways., hCaMKIINalpha suppresses tumor growth by inducing cell cycle arrest via p27 stabilization, Mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/-) have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus, Phosphorylation or a phosphorylation mimicking mutation on NR2B (NR2B-S1303D) abolishes the Ca(2+)/calmodulin-independent binding whereas it allows the Ca(2+)/calmodulin-dependent binding of alpha-CaMKII in vitro., Data show that data provide a novel mechanism whereby CaMKII may regulate the proteasome in neurons to facilitate remodeling of synaptic connections through protein degradation., Knockdown of spinal CaMKIIalpha attentuates opioid-induced hyperalgesia., Data show that he calmodulin-CKII peptide system allows the study of photounbinding under different dissociation constants without changing the molecular system., Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation., 20 single nucleotide polymorphisms had suggestive associations with conduct disorder, nine of which were located in known genes, including CAMK2A, Kv4.3 K channels contribute to cell apoptosis and necrosis through activating CaMKII., A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration., Findigs show that the F-actin-binding protein alpha-actinin-2 targets CaMKIIalpha to F-actin in cells by binding to the CaMKII regulatory domain., The role of CaMKII in regulating GLUT4 expression in skeletal muscle., The decrease in CaMKII signaling in the absence of CAPN3 is associated with a reduction of muscle adaptation response., Inactivating the alphaCamKII transgene eliminates both the IA-type potassium current-mediated firing decrease and the elevated behavioral response to cocaine., Rem2 has a role in neuronal plasticity hrough co-trafficking with CaMKIIa, results suggest that the CAMK2A gene may influence spatial and non-SWM performance in humans without any corresponding gross changes in frontal cortex or hippocampal anatomy., These results suggest that Osterix is a novel target of CaMKII and the activity of Osterix can be modulated by a novel mechanism involving CaMKII during osteoblast differentiation., found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene., we describe for the first time, two patients with MFD and ID and for whom a deletion encompassing TCOF1 and CAMK2A has been identified, CAMK2A SNPs were associated with Alzheimer disease and mild cognitive impairment. AG genotype at the CAMK2A-rs3822606 was associated with AD risk., Overexpression of a T253D phosphomimic form of calcium/calmodulin-dependent protein kinase type II subunit alpha significantly decreases proliferation, and cells accumulate in mitosis, specifically in metaphase., CaMKII-mediated recruitment and upregulation of CYLD is expected to remove K63-linked polyubiquitins and facilitate proteasomal degradation at the postsynaptic density., a novel regulation of CaMKII by another second messenger system and indicate its involvement in excitotoxic neuronal cell death., Ca2+/calmodulin-dependent protein kinase-II (CaMKII) has a key role in the plasticity of glutamatergic synapses of the brain., CaMKII phosphorylates SCN5A in vitro on 23 novel serine sites as was identified by mass spectrometry; reduced S516 phosphorylation has been found in human heart failure.,
OFFICIAL_GENE_SYMBOL CAMK2A,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., enzyme regulation:Autophosphorylation of Thr-286 allows the kinase to switch from a calmodulin-dependent to a calmodulin-independent state., function:CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily., similarity:Contains 1 protein kinase domain., subcellular location:Postsynaptic lipid rafts., subunit:CAMK2 is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits. Interacts with BAALC, MPDZ, SYN1, CAMK2N2 and SYNGAP1.,
calcium/calmodulin dependent protein kinase II beta(CAMK2B) calcium/calmodulin dependent protein kinase II beta(CAMK2B) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 22q12, 22q12|7p14.3-p14.1,
ENSEMBL_GENE_ID ENSG00000058404,
GENERIF_SUMMARY mRNA levels are elevated in the frontal cortex in schizophrenia., Four distinct isoforms of CAMKII were isolated. Two of them were characterized as CaMKII alpha and beta subunits.expression is developmentally regulated in both human fetal and adult brain to different degrees, role in cell communication, CaMK II regulates c-FLIP expression and phosphorylation, thus modulating Fas-mediated signaling in glioma cells, exercise increases the activity of CaMKII in skeletal muscle, suggesting that it may have a role in regulating skeletal muscle function and metabolism during exercise in humans, measured differences in CaMKII binding affinities for CaM play a minor role in the autophosphorylation of the enzyme, largely dictated by autophosphorylation rate for alpha, beta, gamma and delta isoforms, the function of CaMK II is essential for PAF-induced macrophage priming, while CaMK IV is not specific for priming by PAF and appears to have a direct link in TLR4-mediated events, presence of a CaMKIIbeta isoform that can target the SR presumably via its membrane anchor alphaKAP defines a previously unrecognized Ca2+/CaM regulatory system in myocardium, thrombomodulin induces Ca2+ signals and nitric oxide synthesis through EGFR and calmodulin kinase II, expression significantly elevated in frontal cortex in schizophrenia & depression; because CaMKIIbeta influences expression of neuroreceptors & neural outgrowth & pruning, altered expression in schizophrenia or depression may contribute to these diseases, The expression of CaMKII beta was significantly elevated in schizophrenia and in depression., Regulated degradation of liprinalpha1 is important for proper LAR receptor distribution, and could provide a mechanism for localized control of dendrite and synapse morphogenesis by activity and CaMKII., These FLIM versions of Camui could be useful for elucidating the function of CaMKII both in vitro and in vivo., The novel cGMP/PKG/ROS/calmodulin/CaMKII signaling pathway may regulate cardiomyocyte excitability by opening K(ATP) channels and contribute to cardiac protection against ischemia-reperfusion injury., Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation., Promoter methylations of CAMK2B and ARFGEF1 are novel epigenetic markers identified in breast cancer cell lines., Study presents the crystal structure of an autoinhibited full-length human CaMKII holoenzyme, revealing an unexpected compact arrangement of kinase domains docked against a central hub, with the calmodulin-binding sites completely inaccessible., beta-carotene reverses the IL-1beta-mediated reduction in paraoxonase-1 expression via induction of the CaMKKII pathway in human endothelial cells, Due to similarity of structure variations, we suggest that these compounds may have an effect on beta-CaMKII and that sengesterone may have a similar efficacy as the control.,
OFFICIAL_GENE_SYMBOL CAMK2B,
SP_COMMENT alternative products:The variable region of the CAMK2B protein is encoded by at least 7 exons (V1 to V7). Alternative splicing within this region gives rise to CAMK2B isoforms, catalytic activity:ATP + a protein = ADP + a phosphoprotein., enzyme regulation:Autophosphorylation of CAMK2 plays an important role in the regulation of the kinase activity., function:CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release. Member of the NMDAR signaling complex in excitatory synapses, it may regulate NMDAR-dependent potentiation of the AMPAR and synaptic plasticity., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily., similarity:Contains 1 protein kinase domain., subunit:CAMK2 is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits. Interacts with SYNGAP1 and CAMK2N2 (By similarity). Interacts with MPDZ., tissue specificity:Widely expressed. Expressed in adult and fetal brain. Expression is slightly lower in fetal brain.,
calcium/calmodulin dependent protein kinase II delta(CAMK2D) calcium/calmodulin dependent protein kinase II delta(CAMK2D) Related Genes Homo sapiens
CHROMOSOME 4,
CYTOBAND 4q26,
ENSEMBL_GENE_ID ENSG00000145349,
GENERIF_SUMMARY role in cell communication, measured differences in CaMKII binding affinities for CaM play a minor role in the autophosphorylation of the enzyme, largely dictated by autophosphorylation rate for alpha, beta, gamma and delta isoforms, HDAC4 as a specific downstream substrate of CaMKIIdeltaB in cardiac cells and have broad applications for the signaling pathways leading to cardiac hypertrophy and heart failure., Chronic upregulation/activation of CaMKIID, and PKD in heart failure shifts HDAC5 out of the nucleus, derepressing transcription of hypertrophic genes., The cloned, expressed CAMK2delta6 protein comigrated with D52 kinase and colocalized with D52 protein in T84 and HEK293 cells. These findings support a role for CAMK2delta6 in the mediation of D52 phosphorylation., Calcium/Calmodulin-dependent protein kinase II delta 6 (CaMKIIdelta6) and RhoA is involved in thrombin-induced endothelial barrier dysfunction, The crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, is described., This study shows for the first time that CAMKII inhibition acutely improves contractility in human heart failure where CAMKIIdelta expression is increased., Single nucleotide polymorphism in CAMK2D gene is associated with epithelial ovarian cancer., Data show that Pcp4 overexpression induces precocious neuronal differentiation, and is associated with an increase in CaMKIIdelta activation., suggest that CaMKII and calcineurin provide a switch-like mechanism that controls Ca-dependent LIMK1, SSH1L and cofilin activation, and subsequently actin cytoskeletal reorganization, End-stage failing human hearts had more phosphorylation at CaMKII-dependent titin sites, contributing to their mechanical dysfunction & establishing a new role for CaMKIIdelta in regulating diastolic passive properties of healthy & diseased hearts., Our studies suggest that CaMKII is a molecular signal that couples increased reactive oxygen species with atrial fibrillation and that therapeutic strategies to decrease oxidized CaMKII may prevent or reduce it., CAMKIIdelta is required for PP1gamma-exacerbated apoptosis of cardiomyocytes., CaMKIID specifically phosphorylates Thr-457 on CEACAM1-SF, which in turn regulates the process of lumen formation via apoptosis of the central acinar cells., This study showed that AKAP12,CAMK2D and a molecular pathway(cyclic amp)association to outcome of depressive during citalopram treatment., Study found a significant association with disordered gambling and rs167771 (DRD3) and with rs381572 (CAMK2D) in humans, Reveal a novel in vivo function of CaMKIIdelta in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIdelta controls cardiac hypertrophy., CaMKIId activity is up-regulated in the myocardium of diabetic patients and mouse models of diabetes, where it promotes pathological signaling that includes hypertrophy, fibrosis and apoptosis.,
OFFICIAL_GENE_SYMBOL CAMK2D,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., enzyme regulation:Autophosphorylation of CAMK2 plays an important role in the regulation of the kinase activity., function:CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release., miscellaneous:Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily., similarity:Contains 1 protein kinase domain., subunit:CAMK2 is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits., 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.,
calcium/calmodulin dependent protein kinase II gamma(CAMK2G) calcium/calmodulin dependent protein kinase II gamma(CAMK2G) Related Genes Homo sapiens
CHROMOSOME 10,
CYTOBAND 10q22,
ENSEMBL_GENE_ID ENSG00000148660,
GENERIF_SUMMARY role in cell communication, cloning, genomic structure and detection of variants in subjects with Type II diabetes, measured differences in CaMKII binding affinities for CaM play a minor role in the autophosphorylation of the enzyme, largely dictated by autophosphorylation rate for alpha, beta, gamma and delta isoforms, CaMKIIgamma is necessary to suppress MCAK depolymerase activity in vivo., A transgenic, constitutively active, Ca2+-independent form of CaMKgamma reduces positive selection of T cells by maintaining association of SHP-2 with the T cell receptor (TCR) complex, and halting TCR signaling., Amphetamine in a cell line induces a robust increase in cytosolic Ca2+ and concomitant activation of calcium/calmodulin-dependent protein kinase II (CaMKII)., Significant cross-talk between calcium and retinoic acid signaling pathways regulates the differentiation of myeloid leukemia cells., insulin in the presence of Angiotensin II inhibits protein phosphatase-2A (PP-2A) and stimulates autonomous CaM kinase II activities and thus vascular smooth muscle migration, IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Galphaq interaction and protein kinase C-alpha/CaMKII activation in H9c2 cardiomyoblast cells., CaMKIIgamma is a critical regulator of multiple signaling networks regulating the proliferation of myeloid leukemia cells, In Turner yndrome, loss of voltage-dependent inactivation is an upstream initiating event for arrhythmia phenotypes that are ultimately dependent on CaMKII activation., increased RyR2-dependent Ca2+ leakage due to enhanced CaMKII activity is an important downstream effect of CaMKII in individuals susceptible to AF induction., These data demonstrate that alphaKAP exhibits a novel interaction with SERCA2a and may serve to spatially position CaMKII isoforms at the SR and to uniquely modulate the phosphorylation of PLN., P2X7 receptor-triggered signalling pathways that regulate neurite formation in neuroblastoma cells., Study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism that involves inter-holoenzyme T286-region/T-site interaction., The interaction between CaMKII and its binding proteins was altered by the phosphorylation state of both the CaMKII and the partner., CaMKII is a molecular link translating intracellular calcium changes, which are intrinsically associated with glioma migration, to changes in ClC-3 conductance required for cell movement, Our results suggest a first observation that CaMKII regulates TRAIL-mediated apoptosis of fibroblast-like synovial cells through Akt, standing an upstream of caspase-8-dependent cascades., These results indicated that PP6 and CaMKII regulated apoptosis by controlling the expression level of p27., Ca(2+)/calmodulin-dependent kinase II participate in control of cell cycle progression and survival of irradiated CML cells., study shows CaMKII is recruited to the immunological synapse where it interacts with and phosphorylates Bcl10; propose a mechanism whereby Ca(2+) signals can be integrated at the immunological synapse through CaMKII-dependent phosphorylation of Bcl10, increases in Ca(2+) lead to CaMKII activation and subsequent Lck-dependent p66Shc phosphorylation on Serine 36. This event causes both mitochondrial dysfunction and impaired Ca(2+) homeostasis, which synergize in promoting Jurkat T-cell apoptosis., study demonstrates that premitotic condensation involves the activation of ClC-3 by Ca(2+)/calmodulin-dependent protein kinase II in glioma cells, CaMKII binding to and phosphorylation of the NHE3 C terminus are parts of the physiologic regulation of NHE3 that occurs in fibroblasts as well as in the brush border of an intestinal Na(+)-absorptive cell., CaMKII was also necessary for the phosphorylation of Raf-1 at S338 by serum, fibronectin and Ras., we review the cellular colocalization of CaMKII isoforms with special regard to the cell-type specificity of isoform expression in brain--REVIEW, 75-84% of wild type)., These findings revealed a fundamental role of CaMKII in the enteric nervous system., The CaMKII phosphorylation motif in the Nav1.5 DI-DII cytoplasmic loop is a critical point for proarrhythmic changes., Data indicate that CaMKII gamma as a specific and critical target of berbamine for its antileukemia activity., results show that CAMKII and calmodulin contribute to IKK complex activation and thus to the induction of NF-kappaB in response to H. pylori infection, Activated CaMK-II interacts with the C-terminal domain of diacylglycerol lipase-alpha (DGLalpha) and inhibits DGLalpha activity., the chronic gain-of-function defect in RyR2 due to CaMKII hyperphosphorylation is a novel mechanism that contributes to pathogenesis of type 2 diabetes, CaMKII overexpression in mushroom body neurons increases activity dependent calcium responses., Our data suggest that berbamine and its derivatives are promising agents to suppress liver cancer growth by targeting CAMKII, it can be concluded that CaMKII regulates the activity of ASIC1, which is associated with the ability of GBM cells to migrate., our findings described a previously uncharacterized role of CaMKIIgamma in non-small cell lung cancer, CAMKIIgamma, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease., When inhibiting CaMKII, B-cell activating factor (BAFF) is attenuated and mediates protein phosphatase (PP)2A-Erk1/2 signaling and B-cell proliferation., CaMKII-dependent microtube polymerization may be responsible for the enhanced uptake of PEI/ON complexes in A549 cells under oxidative stress conditions., Inhibition of CaMKII activity results in an upregulation of CaMKIV mRNA and protein in leukemia cell lines., Dysfunction in CaMKII-based signaling has been linked with a host of cardiovascular phenotypes including heart failure and arrhythmia, and CaMKII levels are elevated in human and animal disease models of heart disease., High CaMKIIgamma expression is associated with lung cancer., Demonstrate that calcium/CaMKIIgamma/AKT signaling can regulate apoptosis and autophagy simultaneously in colorectal cancer cells.,
OFFICIAL_GENE_SYMBOL CAMK2G,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., enzyme regulation:Autophosphorylation of CAMK2 plays an important role in the regulation of the kinase activity., function:CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily., similarity:Contains 1 protein kinase domain., subunit:CAMK2 is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits.,