Gene Report
Basic Information
| Approved Symbol | CAMK2A |
|---|---|
| Approved Name | calcium/calmodulin-dependent protein kinase II alpha |
| Previous Symbol | CAMKA |
| Previous Name | "calcium/calmodulin-dependent protein kinase (CaM kinase) II alpha" |
| Symbol Alias | KIAA0968, CaMKIINalpha |
| Name Alias | "CaM-kinase II alpha chain", "calcium/calmodulin-dependent protein kinase II alpha-B subunit", "CaM kinase II alpha subunit", "CaMK-II alpha subunit", "calcium/calmodulin-dependent protein kinase type II alpha chain" |
| Location | 5q32 |
| Position | chr5:149669189-149669403 (-) |
| External Links |
Entrez Gene: 815 Ensembl: ENSG00000070808 UCSC: uc003lrt.2 HGNC ID: 1460 |
| No. of Studies (Positive/Negative) | 1(1/0)
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| Type | Literature-origin; Protein mapped |
Positive relationships between CAMK2A and MDD (count: 1)
| Name in Literature | Reference | Research Type | Statistical Result | Relation Description | |
|---|---|---|---|---|---|
| Calcium/calmodulin-dependent protein kinase IIA | Lima, 2002 | patients and normal controls | Genes differentially expressed in major depression Genes differentially expressed in major depression |
Positive relationships between CAMK2A and other components at different levels (count: 0)
Positive relationship network of CAMK2A in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
| Genetic/Epigenetic Locus | Protein and Other Molecule | Cell and Molecular Pathway | Neural System | Cognition and Behavior | Symptoms and Signs | Environment | MDD |
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2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between CAMK2A and MDD (count: 0)
Negative relationships between CAMK2A and other components at different levels (count: 0)
CAMK2A related SNPs in MK4MDD (count: 0)
CAMK2A related proteins in MK4MDD (count: 1)
| Approved Name | UniportKB | No. of Studies (Positive/Negative) | Source | |
|---|---|---|---|---|
| Calcium/calmodulin-dependent protein kinase type II subunit alpha | Q9UQM7 | 1(1/0) | Literature-origin |
CAMK2A related GO terms (count: 52)
Literature-origin GO terms | ||||
| ID | Name | Type | Evidence | |
|---|---|---|---|---|
| GO:0030054 | cell junction | cellular component | IEA | |
| GO:0007268 | synaptic transmission | biological process | TAS | |
| GO:0016301 | kinase activity | molecular function | IDA[17052756] | |
| GO:0000165 | MAPK cascade | biological process | TAS | |
Gene mapped GO terms | ||||
| ID | Name | Type | Evidence | |
|---|---|---|---|---|
| GO:0035254 | glutamate receptor binding | molecular function | ISS | |
| GO:0007265 | Ras protein signal transduction | biological process | TAS | |
| GO:0042734 | presynaptic membrane | cellular component | IEA | |
| GO:0048168 | regulation of neuronal synaptic plasticity | biological process | ISS | |
| GO:0038166 | angiotensin-activated signaling pathway | biological process | IDA[20584908] | |
| GO:0005829 | cytosol | cellular component | TAS | |
| GO:1902108 | regulation of mitochondrial membrane permeability involved in apoptotic process | biological process | ISS | |
| GO:0006468 | protein phosphorylation | biological process | IDA[17052756] | |
| GO:0004683 | calmodulin-dependent protein kinase activity | molecular function | IEA | |
| GO:0097481 | neuronal postsynaptic density | cellular component | IEA | |
| GO:0005739 | mitochondrion | cellular component | ISS | |
| GO:0007411 | axon guidance | biological process | TAS | |
| GO:0005886 | plasma membrane | cellular component | TAS | |
| GO:0004674 | protein serine/threonine kinase activity | molecular function | ISS | |
| GO:0034605 | cellular response to heat | biological process | TAS | |
| GO:0032553 | ribonucleotide binding | molecular function | IEA | |
| GO:0032553 | ribonucleotide binding | molecular function | IEA | |
| GO:0032553 | ribonucleotide binding | molecular function | IEA | |
| GO:0018105 | peptidyl-serine phosphorylation | biological process | ISS | |
| GO:0006816 | calcium ion transport | biological process | ISS | |
| GO:0000082 | G1/S transition of mitotic cell cycle | biological process | ISS | |
| GO:0000186 | activation of MAPKK activity | biological process | TAS | |
| GO:0046777 | protein autophosphorylation | biological process | ISS | |
| GO:0008286 | insulin receptor signaling pathway | biological process | TAS | |
| GO:0051928 | positive regulation of calcium ion transport | biological process | ISS | |
| GO:0048011 | neurotrophin TRK receptor signaling pathway | biological process | TAS | |
| GO:0005515 | protein binding | molecular function | IPI[17052756|19453375] | |
| GO:0048010 | vascular endothelial growth factor receptor signaling pathway | biological process | TAS | |
| GO:0005654 | nucleoplasm | cellular component | TAS | |
| GO:1900034 | regulation of cellular response to heat | biological process | TAS | |
| GO:0005524 | ATP binding | molecular function | IEA | |
| GO:0007264 | small GTPase mediated signal transduction | biological process | TAS | |
| GO:0046928 | regulation of neurotransmitter secretion | biological process | ISS | |
| GO:0010666 | positive regulation of cardiac muscle cell apoptotic process | biological process | ISS | |
| GO:0060333 | interferon-gamma-mediated signaling pathway | biological process | TAS | |
| GO:0030666 | endocytic vesicle membrane | cellular component | TAS | |
| GO:0007173 | epidermal growth factor receptor signaling pathway | biological process | TAS | |
| GO:0032553 | ribonucleotide binding | molecular function | IEA | |
| GO:0008543 | fibroblast growth factor receptor signaling pathway | biological process | TAS | |
| GO:0002931 | response to ischemia | biological process | ISS | |
| GO:0005516 | calmodulin binding | molecular function | IPI[20668654] | |
| GO:0019221 | cytokine-mediated signaling pathway | biological process | TAS | |
| GO:0042803 | protein homodimerization activity | molecular function | IPI[20668654] | |
| GO:0032553 | ribonucleotide binding | molecular function | IEA | |
| GO:0045087 | innate immune response | biological process | TAS | |
| GO:0005634 | nucleus | cellular component | IDA[21630459] | |
| GO:0038095 | Fc-epsilon receptor signaling pathway | biological process | TAS | |
| GO:0051092 | positive regulation of NF-kappaB transcription factor activity | biological process | IMP[17052756] | |
CAMK2A related KEGG pathways (count: 10)
Literature-origin KEGG pathway | ||||
| ID | Name | Brief Description | Full Description | |
|---|---|---|---|---|
| hsa04020 | calcium signaling_pathway | Calcium signaling pathway | Ca2+ that enters the cell from the outside is a principal so...... Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs). The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it. The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM). More... | |
Gene mapped KEGG pathways | ||||
| ID | Name | Brief Description | Full Description | |
|---|---|---|---|---|
| hsa04114 | oocyte meiosis | Oocyte meiosis | During meiosis, a single round of DNA replication is followe...... During meiosis, a single round of DNA replication is followed by two rounds of chromosome segregation, called meiosis I and meiosis II. At meiosis I, homologous chromosomes recombine and then segregate to opposite poles, while the sister chromatids segregate from each other at meoisis II. In vertebrates, immature oocytes are arrested at the PI (prophase of meiosis I). The resumption of meiosis is stimulated by progesterone, which carries the oocyte through two consecutive M-phases (MI and MII) to a second arrest at MII. The key activity driving meiotic progression is the MPF (maturation-promoting factor), a heterodimer of CDC2 (cell division cycle 2 kinase) and cyclin B. In PI-arrested oocytes, MPF is initially inactive and is activated by the dual-specificity CDC25C phosphatase as the result of new synthesis of Mos induced by progesterone. MPF activation mediates the transition from the PI arrest to MI. The subsequent decrease in MPF levels, required to exit from MI into interkinesis, is induced by a negative feedback loop, where CDC2 brings about the activation of the APC (anaphase-promoting complex), which mediates destruction of cyclin B. Re-activation of MPF for MII requires re-accumulation of high levels of cyclin B as well as the inactivation of the APC by newly synthesized Emi2 and other components of the CSF (cytostatic factor), such as cyclin E or high levels of Mos. CSF antagonizes the ubiquitin ligase activity of the APC, preventing cyclin B destruction and meiotic exit until fertilization occurs. Fertilization triggers a transient increase in cytosolic free Ca2+, which leads to CSF inactivation and cyclin B destruction through the APC. Then eggs are released from MII into the first embryonic cell cycle. More... | |
| hsa04310 | wnt signaling_pathway | Wnt signaling pathway | Wnt proteins are secreted morphogens that are required for b...... Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin. More... | |
| hsa04720 | long term_potentiation | Long-term potentiation | Hippocampal long-term potentiation (LTP), a long-lasting inc...... Hippocampal long-term potentiation (LTP), a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. Tetanic stimulation of afferents in the CA1 region of the hippocampus induces glutamate release and activation of glutamate receptors in dendritic spines. A large increase in i resulting from influx through NMDA receptors leads to constitutive activation of CaM kinase II (CaM KII). Constitutively active CaM kinase II phosphorylates AMPA receptors, resulting in potentiation of the ionic conductance of AMPA receptors. Early-phase LTP (E-LTP) expression is due, in part, to this phosphorylation of the AMPA receptor. It is hypothesized that postsynaptic Ca2+ increases generated through NMDA receptors activate several signal transduction pathways including the Erk/MAP kinase and cAMP regulatory pathways. The convergence of these pathways at the level of the CREB/CRE transcriptional pathway may increase expression of a family of genes required for late-phase LTP (L-LTP). More... | |
| hsa04740 | olfactory transduction | Olfactory transduction | Within the compact cilia of the olfactory receptor neurons (...... Within the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be transmitted to the brain. Odorant molecules bind to a receptor protein (R) coupled to an olfactory specific Gs-protein (G) and activate a type III adenylyl cyclase (AC), increasing intracellular cAMP levels. cAMP targets an olfactory-specific cyclic-nucleotide gated ion channel (CNG), allowing cations, particularly Na and Ca, to flow down their electrochemical gradients into the cell, depolarizing the ORN. Furthermore, the Ca entering the cell is able to activate a Ca-activated Cl channel, which would allow Cl to flow out of the cell, thus further increasing the depolarization. Elevated intracellular Ca causes adaptation by at least two different molecular steps: inhibition of the activity of adenylyl cyclase via CAMKII-dependent phosphorylation and down-regulation of the affinity of the CNG channel to cAMP.Longer exposure to odorants can stimulate particulate guanylyl cyclase in cilia to produce cGMP and activate PKG, leading to a further increase in amount and duration of intracellular cAMP levels, which may serve to convert inactive forms of protein kinase A (PKA2) to active forms (PKA*). As part of a feedback loop, PKA can inhibit the activation of particulate guanylyl cyclase. More... | |
| hsa04916 | melanogenesis | Melanogenesis | Cutaneous melanin pigment plays a critical role in camouflag...... Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism. More... | |
| hsa05214 | glioma | Glioma | Glioblastoma multiforme (GBM) formation is either de novo (p...... Glioblastoma multiforme (GBM) formation is either de novo (primary GBMs) or due to the progression of a lower grade glioma to a higher grade one through the acquisition of additional mutations (secondary GBMs). In primary GBM, disruption of the p53 pathway often occurs through loss of ARF, or less frequently through amplification of MDM2. Disruption of the RB pathway occurs through loss of INK4A. Amplification and/or mutation of the epidermal growth factor receptor (EGFR) is the most frequently detected genetic defect that is associated with primary GBM. In secondary GBM, loss of p53 and activation of the growth-factorreceptor-tyrosine-kinase signalling pathway (such as through overexpression of PDGF/PDGFR ) initiates tumour formation,whereas disruption of the retinoblastoma (RB) pathway contributes to the progression of tumour development. Loss of PTEN has been implicated in both pathways, although it is much more common in the pathogenesis of primary GBM. More... | |
| hsa04722 | neurotrophin signaling_pathway | Neurotrophin signaling pathway | Neurotrophins are a family of trophic factors involved in di...... Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory. More... | |
| hsa04912 | gnrh signaling_pathway | GnRH signaling pathway | Gonadotropin-releasing hormone (GnRH) secretion from the hyp...... Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes. More... | |
| hsa04012 | erbb signaling_pathway | ErbB signaling pathway | The ErbB family of receptor tyrosine kinases (RTKs) couples ...... The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. Similarly, the phosphatidylinositol-3-kinase (PI-3K) pathway is directly or indirectly activated by most ErbBs. Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase. More... | |
CAMK2A related BioCarta pathways (count: 5)
Gene mapped BioCarta pathways | ||||
| ID | Name | Brief Description | Full Description | |
|---|---|---|---|---|
| BIOPEPTIDES_PATHWAY | biopeptides pathway | Bioactive Peptide Induced Signaling Pathway | Many different peptides act as signaling molecules, includin...... Many different peptides act as signaling molecules, including the proinflammatory peptide bradykinin, the protease enzyme thrombin, and the blood pressure regulating peptide angiotensin. While these three proteins are distinct in their sequence and physiology, and act through different cell surface receptors, they share in a common class of cell surface receptors called G-protein coupled receptors (GPCRs). Other polypeptide ligands of GPCRs include vasopressin, oxytocin, somatostatin, neuropeptide Y, GnRH, leutinizing hormone, follicle stimulating hormone, parathyroid hormone, orexins, urotensin II, endorphins, enkephalins, and many others. GPCRs are a broad and diverse gene family that respond not only to peptide ligands but also small molecule neurotransmitters (acetylcholine, dopamine, serotonin and adrenaline), light, odorants, taste, lipids, nucleotides, and ions. The main signaling mechanism used by GPCRs is to interact with G-protein GTPase proteins coupled to downstream second messenger systems including intracellular calcium release and cAMP production. The intracellular signaling systems used by peptide GPCRs are similar to those used by all GPCRs, and are typically classified according to the G-protein they interact with and the second messenger system that is activated. For Gs-coupled GPCRs, activation of the G-protein Gs by receptor stimulates the downstream activation of adenylate cyclase and the production of cyclic AMP, while Gi-coupled receptors inhibit cAMP production. One of the key results of cAMP production is activation of protein kinase A. Gq-coupled receptors stimulate phospholipase C, releasing IP3 and diacylglycerol. IP3 binds to a receptor in the ER to cause the release of intracellular calcium, and the subsequent activation of protein kinase C, calmodulin-dependent pathways. In addition to these second messenger signaling systems for GPCRs, GPCR pathways exhibit crosstalk with other signaling pathways including tyrosine kinase growth factor receptors and map kinase pathways. Transactivation of either receptor tyrosine kinases like the EGF receptor or focal adhesion complexes can stimulate ras activation through the adaptor proteins Shc, Grb2 and Sos, and downstream Map kinases activating Erk1 and Erk2. Src kinases may also play an essential intermediary role in the activation of ras and map kinase pathways by GPCRs. More... | |
| CREB_PATHWAY | creb pathway | Transcription factor CREB and its extracellular signals | The transcription factor CREB binds the cyclic AMP response ...... The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity. Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133. Phosphorylation occurs at Ser133 via p44/42 MAP Kinase and p90RSK and also via p38 MAP Kinase and MSK1. CREB exhibit deficiencies in spatial learning tasks, while flies overexpressing or lacking CREB show enhanced or diminished learning, respectively. More... | |
| PGC1A_PATHWAY | pgc1a pathway | Regulation of PGC-1a | Peroxisome proliferator-activated receptor gamma coactivator...... Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a tissue-specific coactivator that enhances the activity of many nuclear receptors and coordinates transcriptional programs important for energy metabolism and energy homeostasis. Inappropriate increases in PGC-1a activity have been linked to a number of pathological conditions including heart failure and diabetes. PGC-1a is highly expressed in metabolically active tissues including brown fat, skeletal muscle and heart. PGC-1a has been implicated in mitochondrial biogenesis in the heart and increased mitochondrial respiration in brown fat. PGC-1a is a coactivator for many factors including, CBP, Scr-1, PPARa, GR (glucocorticoid receptor), THR (thyroid hormone receptor), several orphan receptors and MEF2. This pathway illustrates two of the cofactor regulatory factors MEF2 and PPARa) and an example orphan receptor feedback inhibition loop. Glut4 is used as an example of the downstream elements leading to changes in metabolism. Ichida et al discovered the ERRa repression of PGC-1a. Their results suggest a novel mechanism of transcriptional control wherein ERR-a can function as a specific molecular repressor of PGC-1a. This suggests that other co-activators might also have specific repressors, adding another layer of combinatorial complexity in transcriptional regulation. Czubryt et al identified PGC-1 a as a key target of the MEF2/HDAC regulatory pathway and demonstrated this pathway's importance in maintenance of cardiac mitochondrial function. The linking of MEF2/HDAC provides an potential explanation for the increase in mitochondrial number observed in response to CaMK signaling. More... | |
| CACAM_PATHWAY | cacam pathway | Ca++/ Calmodulin-dependent Protein Kinase Activation | The calcium/calmodulin-dependent kinases (CaMKs) are involve...... The calcium/calmodulin-dependent kinases (CaMKs) are involved in a large number of cellular responses induced by hormones, neurotransmitters and other signalling. Elevation of calcium functions as a major second messenger, where the intracellular concentration of calcium can be maintained at extremely low levels and susequently increased following specific calcium-mobilizing stimuli. There are many buffers to the calcium fluxuations including membrane pumps and calcium-binding proteins that create discrete spatial control of its effectors and their targets. The current family of multifunctional calcium/calmodulin (CaM)-dependent protein kinases (CaMKs) consists of CaMKI, CaMKII and CaMKIV. These kinases translate and co-ordinate the calcium fluxuations into the appropriate cellular responses via phosphorylation. These kinases are partially regulated by the intracellular calcium receptor calmodulin (CaM), have common as well as unique features in their structure, regulation and activation. CaMKII, CaMKI and CaMKIV, have an autoregulatory domain that restricts or inhibits enzymic activity in the absence of calcium/CaM. Calcium/CaM binding alone produces maximal activity of CaMKII, whereas CaMKI and CaMKIV have an activation loop that requires phosphorylation of a threonine residue by CaMK kinase (CaMKK) for maximal activity. Two genes (alpha and beta) for CaMKK, which is also regulated by CaM, have been identified. The highest expression of these isoforms occurs in the brain but the activity of the CaMKs has been identified in most cell types. CaMKIV has a post-calmodulin autophosphorylation step that is not observed in CaMKI. The CaMKII multimer can autophosphorylate either the autoregulatory domain or the CaM-binding domain, producing diverse effects in its regulation and sensitivity to Calcium/CaM. Autophosphorylation of CaMKII can produce Calcium/CaM- independent activity (autonomous activity), without affecting its maximal Calcium/CaM-stimulated activity. The CaMKII autophosphorylation involves a kinase cascade of sorts, with each subunit of the multimeric enzyme acting as both kinase and kinase kinase. Autophosphorylation establishes a 1000-fold increase in the affinity for its activator Calcium/CaM (also known as CaM trapping); however, autophosphorylation within the CaM-binding domain following CaM dissociation of activated/autophosphorylated enzyme restricts or prevents CaM from rebinding (CaM capping). The mechanisms and consequences of autophosphorylation are central to the CaMKII enzyme's complex regulatory behavior enabling it to become differentially activated at different frequencies and levels of calcium spikes. The target proteins for the CaMKs are very similar. An example target of the CaMKs is the transcriptional activating protein CREB. The phosphorylation states of CREB after CaMK phosphorlyation differ by the additional phosphorylation of CREB at serine 142 that functions as an additional inhibitory site. This difference appears to be the result of adjacent amino acids. More... | |
| STATHMIN_PATHWAY | stathmin pathway | Stathmin and breast cancer resistance to antimicrotubule agents | Stathmin is a ubiquitous, cytosolic 19-kDa protein, which is...... Stathmin is a ubiquitous, cytosolic 19-kDa protein, which is phosphorylated on up to four sites in response to many regulatory signals within cells. Its molecular characterization indicates a functional organization including an N-terminal regulatory domain that bears the phosphorylation sites, linked to a putative alpha-helical binding domain predicted to participate in coiled-coil, protein-protein interactions. In addtion to the protein kinases that phospjhorylate Stathmin such as CaMK, MAPK, p34cdc2, PKA, a few other proteins have been suggested to interact with stathmin in vivo. One of them was identified as BiP, a member of the hsp70 heat-shock protein family. Another is a previously unidentified, putative serine/threonine kinase, KIS, which might be regulated by stathmin or, more likely, be part of the kinases controlling its phosphorylation state. Finally, two proteins, CC1 and CC2, predicted to form alpha-helices participating in coiled-coil interacting structures. It has been also suggest that the action of antimicrotubule drugs can be affected by stathmin in at least two ways: (a) altered drug binding; and (b) growth arrest at the G2 to M boundary. Mutant p53 breast cancers exhibiting high levels of stathmin may be resistant to antimicrotubule agents. More... | |
CAMK2A related Reactome pathways (count: 8)
Gene mapped Reactome pathways | |||
| ID | Name | Description | |
|---|---|---|---|
| REACT_15370 | neuroransmitter receptor_binding_and_downstream_transmission_in_the_postsynaptic_cell | The neurotransmitter in the synaptic cleft released by the p...... The neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein coupled receptors that function to transmit the signals from the post-synaptic membrane to the cell body. More... | |
| REACT_20563 | activation of_nmda_receptor_upon_glutamate_binding_and_postsynaptic_events | NMDA receptors are a subtype of ionotropic glutamate recepto...... NMDA receptors are a subtype of ionotropic glutamate receptors that are specifically activated by a glutamate agonist N-methyl-D-aspartate (NMDA). Activation of NMDA receptor involves opening of the ion channel that allows the influx of Ca2+. NMDA receptors are central to activity dependent changes in synaptic strength and are predominantly involved in the synaptic plasticity that pertain to learning and memory. A unique feature of NMDA receptor unlike other glutamate receptors is the requirement of dual activation of the NMDA receptor, which require both voltage dependent and ligand dependent activation. At resting membrane potential the NMDA receptors are blocked by Mg2+. The voltage dependent Mg2+ block is relieved upon depolarization of the post-synpatic membrane. The ligand dependent activation of the NMDA receptor requires co-activation by two ligands, namely glutamate and glycine. NMDA receptors are coincidence detector, and are activated only if there is simultaneous activation of both pre and post-synaptic cell. Upon activation NMDA receptors allow the influx of Ca2+ that initiates various molecular signaling cascades that are involved in the process of learning and memory. More... | |
| REACT_13477 | transmission across_chemical_synapses | Chemical synapses are specialized junctions that are used fo...... Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell. More... | |
| REACT_20546 | ras activation_uopn_ca2_infux_through_nmda_receptor | Ca2+ influx through the NMDA receptor leads to the activatio...... Ca2+ influx through the NMDA receptor leads to the activation of Ras kinase via the activation of RasGRF. More... | |
| REACT_20593 | post nmda_receptor_activation_events | Ca2+ influx through the NMDA receptor initiates subsequent m...... Ca2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca2+ within the spine leads to phosphorylation of Cyclic AMP Response Element binding protein (CREB) at serine 133 which is involved in the transcription of genes that results in long lasting changes in the synapse. The phosphorylation of CREB by increased Ca2+ can be brought about by distinct molecular pathways that may involve MAP kinase, activation of adenylate cyclase, activation of CaMKII and/or the activation of CaMKIV. More... | |
| REACT_20642 | creb phosphorylation_through_the_activation_of_camkii | Ca2+ signal generated through NMDA receptor in the post-syna...... Ca2+ signal generated through NMDA receptor in the post-synaptic neuron activates adenylate cyclase signal transduction, leading to the activation of PKA and phosphorylation and activation of CREB-induced transcription. The isoforms of adenylate cyclase that are activated by Ca2+ in the brain are I, III and IX. More... | |
| REACT_18307 | trafficking of_ampa_receptors | Repetitive presynaptic activity causes long lasting changes ...... Repetitive presynaptic activity causes long lasting changes in the postsynaptic transmission by changing the type and the number of AMPA receptors. These changes are brought about by trafficking mechanisms that are mainly controlled by activity dependent phosphorylation/desphosphorylation of the GluR1/GluR2 subunits. More... | |
| REACT_20568 | creb phophorylation_through_the_activation_of_ras | Ca2+ influx through the NMDA receptor initiates subsequent m...... Ca2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca2+ within the spine leads to phosphorylation of Cyclic AMP Response Element binding protein (CREB) at serine 133 which is involved in the transcription of genes that results in long lasting changes in the synapse. The phosphorylation of CREB by increased Ca2+ can be brought about by distinct molecular pathways that may involve MAP kinase, activation of adenylate cyclase, activation of CaMKII and/or the activation of CaMKIV. More... | |
CAMK2A related interactors from protein-protein interaction data in HPRD (count: 32)