Gene Report
Basic Information
| Approved Symbol | CACNA1C |
|---|---|
| Approved Name | calcium channel, voltage-dependent, L type, alpha 1C subunit |
| Previous Symbol | CCHL1A1, CACNL1A1 |
| Symbol Alias | Cav1.2, CACH2, CACN2, TS, LQT8 |
| Location | 12p13.3 |
| Position | chr12:2162416-2807115 (+) |
| External Links |
Entrez Gene: 775 Ensembl: ENSG00000151067 UCSC: uc001qjy.3 HGNC ID: 1390 |
| No. of Studies (Positive/Negative) | 1(1/0)
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| Type | Literature-origin; SNP mapped |
Positive relationships between CACNA1C and MDD (count: 0)
Positive relationships between CACNA1C and other components at different levels (count: 7)
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Positive relationship network of CACNA1C 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 CACNA1C and MDD (count: 0)
Negative relationships between CACNA1C and other components at different levels (count: 0)
CACNA1C related SNPs in MK4MDD (count: 1)
| #rs | Location | Annotation | No. of Studies (Positive/Negative) | |
|---|---|---|---|---|
| rs1006737 | chr12:2345295(Forward) | intron_variant | 2(2/0) |
CACNA1C related proteins in MK4MDD (count: 1)
| Approved Name | UniportKB | No. of Studies (Positive/Negative) | Source | |
|---|---|---|---|---|
| Voltage-dependent L-type calcium channel subunit alpha-1C | Q13936 | 0(0/0) | Gene mapped |
CACNA1C related GO terms (count: 35)
Literature-origin GO terms | ||||
| ID | Name | Type | Evidence | |
|---|---|---|---|---|
| GO:0007268 | synaptic transmission | biological process | IEA | |
Gene mapped GO terms | ||||
| ID | Name | Type | Evidence | |
|---|---|---|---|---|
| GO:0005886 | plasma membrane | cellular component | IDA[11206130]; TAS | |
| GO:0030018 | Z disc | cellular component | ISS | |
| GO:0008217 | regulation of blood pressure | biological process | IEA | |
| GO:0008542 | visual learning | biological process | IEA | |
| GO:0002095 | caveolar macromolecular signaling complex | cellular component | IEA | |
| GO:0046872 | metal ion binding | molecular function | IEA | |
| GO:0035585 | calcium-mediated signaling using extracellular calcium source | biological process | TAS[11576544] | |
| GO:0046620 | regulation of organ growth | biological process | IEA | |
| GO:0007204 | elevation of cytosolic calcium ion concentration | biological process | IDA[12130699] | |
| GO:0051393 | alpha-actinin binding | molecular function | IPI[17110593] | |
| GO:0006112 | energy reserve metabolic process | biological process | TAS | |
| GO:0007411 | axon guidance | biological process | TAS | |
| GO:0044281 | small molecule metabolic process | biological process | TAS | |
| GO:0014069 | postsynaptic density | cellular component | IDA[14140941] | |
| GO:0019229 | regulation of vasoconstriction | biological process | IEA | |
| GO:0017156 | calcium ion-dependent exocytosis | biological process | IEA | |
| GO:0005516 | calmodulin binding | molecular function | IPI[15140941] | |
| GO:0005891 | voltage-gated calcium channel complex | cellular component | IDA[12130699] | |
| GO:0060083 | smooth muscle contraction involved in micturition | biological process | IEA | |
| GO:0042593 | glucose homeostasis | biological process | IEA | |
| GO:0050796 | regulation of insulin secretion | biological process | TAS | |
| GO:0005245 | voltage-gated calcium channel activity | molecular function | IDA[8392192] | |
| GO:0010881 | regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion | biological process | TAS[11576544] | |
| GO:0043025 | neuronal cell body | cellular component | IEA | |
| GO:0005737 | cytoplasm | cellular component | IDA[11206130] | |
| GO:0086064 | cell communication by electrical coupling involved in cardiac conduction | biological process | TAS[11576544] | |
| GO:0043198 | dendritic shaft | cellular component | IEA | |
| GO:0016021 | integral to membrane | cellular component | IDA[8392192] | |
| GO:0005515 | protein binding | molecular function | IPI[15140941] | |
| GO:0030252 | growth hormone secretion | biological process | IEA | |
| GO:0007628 | adult walking behavior | biological process | IEA | |
| GO:0008331 | high voltage-gated calcium channel activity | molecular function | TAS[11576544] | |
| GO:0030073 | insulin secretion | biological process | IEA | |
| GO:0060402 | calcium ion transport into cytosol | biological process | TAS[19095005] | |
CACNA1C related KEGG pathways (count: 11)
Literature-origin KEGG pathway | ||||
| ID | Name | Brief Description | Full Description | |
|---|---|---|---|---|
| hsa04270 | vascular smooth_muscle_contraction | Vascular smooth muscle contraction | The vascular smooth muscle cell (VSMC) is a highly specializ...... The vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regulate the blood flow and pressure. The principal mechanisms that regulate the contractile state of VSMCs are changes in cytosolic Ca2+ concentration (c). In response to vasoconstrictor stimuli, Ca2+ is mobilized from intracellular stores and/or the extracellular space to increase c in VSMCs. The increase in c, in turn, activates the Ca2+-CaM-MLCK pathway and stimulates MLC20 phosphorylation, leading to myosin-actin interactions and, hence, the development of contractile force. The sensitivity of contractile myofilaments or MLC20 phosphorylation to Ca2+ can be secondarily modulated by other signaling pathways. During receptor stimulation, the contractile force is greatly enhanced by the inhibition of myosin phosphatase. Rho/Rho kinase, PKC, and arachidonic acid have been proposed to play a pivotal role in this enhancement. The signaling events that mediate relaxation include the removal of a contractile agonist (passive relaxation) and activation of cyclic nucleotide-dependent signaling pathways in the continued presence of a contractile agonist (active relaxation). Active relaxation occurs through the inhibition of both Ca2+ mobilization and myofilament Ca2+ sensitivity in VSMCs. More... | |
| hsa05412 | arrhythmogenic right_ventricular_cardiomyopathy_arvc | Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an...... Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVD/C. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death. More... | |
| 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 | |
|---|---|---|---|---|
| hsa04260 | cardiac muscle_contraction | Cardiac muscle contraction | Contraction of the heart is a complex process initiated by t...... Contraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation of voltage-dependent L-type Ca channels (DHP receptors) upon membrane depolarization triggers the release of Ca2+ via Ca2+ release channels (ryanodine receptors) of sarcoplasmic reticulum (SR) through a Ca2+ -induced Ca release (CICR) mechanism. Ca2+ ions released via the CICR mechanism diffuse through the cytosolic space to contractile proteins to bind to troponinC resulting in the release of inhibition induced by troponinI. The Ca2+ binding to troponinC thereby triggers the sliding of thin and thick filaments, that is, the activation of a crossbridge and subsequent cardiac force development and/or cell shortening. Recovery occurs as Ca2+ is pumped out of the cell by the Na+/Ca2+ exchanger (NCX) or is returned to the sarcoplasmic reticulum (SR) by sarco(endo)plasmic Ca2+ -ATPase (SERCA) pumps on the non-junctional region of the SR. More... | |
| hsa05414 | dilated cardiomyopathy | Dilated cardiomyopathy | Dilated cardiomyopathy (DCM) is a heart muscle disease chara...... Dilated cardiomyopathy (DCM) is a heart muscle disease characterised by dilation and impaired contraction of the left or both ventricles that results in progressive heart failure and sudden cardiac death from ventricular arrhythmia. Genetically inherited forms of DCM (familial DCM) have been identified in 25-35% of patients presenting with this disease, and the inherited gene defects are an important cause of familial DCM. The pathophysiology may be separated into two categories: defects in force generation and defects in force transmission. In cases where an underlying pathology cannot be identified, the patient is diagnosed with an idiopathic DCM. Current hypotheses regarding causes of idiopathic DCM focus on chronic viral myocarditis and/or on autoimmune abnormalities. Viral myocarditis may progress to an autoimmune phase and then to progressive cardiac dilatation. Antibodies to the beta1-adrenergic receptor (beta1AR), which are detected in a substantial number of patients with idiopathic DCM, may increase the concentration of intracellular cAMP and intracellular Ca2+, a condition often leading to a transient hyper-performance of the heart followed by depressed heart function and heart failure. More... | |
| hsa04930 | type ii_diabetes_mellitus | Type II diabetes mellitus | Insulin resistance is strongly associated with type II diabe...... Insulin resistance is strongly associated with type II diabetes. Diabetogenic factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Serine/threonine phosphorylation, interaction with SOCS, regulation of the expression, modification of the cellular localization, and degradation represent the molecular mechanisms stimulated by them. Various kinases (ERK, JNK, IKKbeta, PKCzeta, PKCtheta and mTOR) are involved in this process. The development of type II diabetes requires impaired beta-cell function. Chronic hyperglycemia has been shown to induce multiple defects in beta-cells. Hyperglycemia has been proposed to lead to large amounts of reactive oxygen species (ROS) in beta-cells, with subsequent damage to cellular components including PDX-1. Loss of PDX-1, a critical regulator of insulin promoter activity, has also been proposed as an important mechanism leading to beta-cell dysfunction. Although there is little doubt as to the importance of genetic factors in type II diabetes, genetic analysis is difficult due to complex interaction among multiple susceptibility genes and between genetic and environmental factors. Genetic studies have therefore given very diverse results. Kir6.2 and IRS are two of the candidate genes. It is known that Kir6.2 and IRS play central roles in insulin secretion and insulin signal transmission, respectively. More... | |
| hsa04010 | mapk signaling_pathway | MAPK signaling pathway | The mitogen-activated protein kinase (MAPK) cascade is a hig...... The mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals express at least four distinctly regulated groups of MAPKs, extracellular signal-related kinases (ERK)-1/2, Jun amino-terminal kinases (JNK1/2/3), p38 proteins (p38alpha/beta/gamma/delta) and ERK5, that are activated by specific MAPKKs: MEK1/2 for ERK1/2, MKK3/6 for the p38, MKK4/7 (JNKK1/2) for the JNKs, and MEK5 for ERK5. Each MAPKK, however, can be activated by more than one MAPKKK, increasing the complexity and diversity of MAPK signalling. Presumably each MAPKKK confers responsiveness to distinct stimuli. For example, activation of ERK1/2 by growth factors depends on the MAPKKK c-Raf, but other MAPKKKs may activate ERK1/2 in response to pro-inflammatory stimuli. 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... | |
| hsa05410 | hypertrophic cardiomyopathy_hcm | Hypertrophic cardiomyopathy (HCM) | Hypertrophic cardiomyopathy (HCM) is a primary myocardial di...... Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in 11 genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myofilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction. 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... | |
| hsa05010 | alzheimers disease | Alzheimer's disease | Alzheimer's disease (AD) is a chronic disorder that slowly d...... Alzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specifically the more amyloidogenic form, Abeta42. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress. More... | |
CACNA1C related BioCarta pathways (count: 0)
CACNA1C related Reactome pathways (count: 9)
Gene mapped Reactome pathways | |||
| ID | Name | Description | |
|---|---|---|---|
| REACT_1505 | integration of_energy_metabolism | Many hormones that affect individual physiological processes...... Many hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insulin mediates the storage of excess nutrients, glucagon is involved in the mobilization of energy resources in response to low blood glucose levels, principally by stimulating hepatic glucose output. Small doses of glucagon are sufficient to induce significant glucose elevations. These hormone-driven regulatory pathways enable the body to sense and respond to changed amounts of nutrients in the blood and demands for energy. Glucagon and Insulin act through various metabolites and enzymes that target specific steps in metabolic pathways for sugar and fatty acids. The processes responsible for the long-term control of fat synthesis and short term control of glycolysis by key metabolic products and enzymes are annotated in this module as six specific pathways: Pathway 1. Glucagon signalling in metabolic pathways: In response to low blood glucose, pancreatic alpha-cells release glucagon. The binding of glucagon to its receptor results in increased cAMP synthesis, and Protein Kinase A - Copyright National Academy of Sciences, U.S.A.). More... | |
| REACT_16921 | glucose regulation_of_insulin_secretion | Increased blood glucose levels from dietary carbohydrate nor...... Increased blood glucose levels from dietary carbohydrate normally trigger insulin release from the beta cells of the pancreas. Glucose catabolism in the beta cell is the transducer that links increased glucose levels to insulin release. Glucose uptake and glycolysis generate cytosolic pyruvate; pyruvate is transported to mitochondria and converted both to oxaloacetate which increases levels of TCA cycle intermediates, and to acetyl-CoA which is oxidized to CO2 via the TCA cycle. The rates of ATP synthesis and transport to the cytosol increase, plasma membrane ATP-sensitive inward rectifying potassium channels. Elevated calcium concentrations near the plasma membrane cause insulin secretion in two phases: an initial high rate within minutes of glucose stimulation and a slow, sustained release lasting longer than 30 minutes. In the initial phase, 50-100 insulin granules already docked at the membrane are exocytosed. Exocytosis is rendered calcium-dependent by Synaptotagmin V/IX, a calcium-binding membrane protein located in the membrane of the docked granule, although the exact action of Synapototagmin in response to calcium is unknown. Calcium also causes a translocation of reserve granules within the cell towards the plasma membrane for release in the second, sustained phase of secretion. Human cells contain L-type. More... | |
| REACT_18334 | ncam signaling_for_neurite_out_growth | The neural cell adhesion molecule, NCAM, is a member of the ...... The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. The role of NCAM in neural differentiation and synaptic plasticity is presumed to depend on the modulation of intracellular signal transduction cascades. NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons. NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements. More... | |
| REACT_18339 | inhibition of_insulin_secretion_by_adrenaline_noradrenaline | The catecholamines adrenaline (epinephrine) and noradrenalin...... The catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) inhibit insulin secretion from pancreatic beta cells. Four effects are seen in the cells: 1. Inhibition of exocytosis of secretory granules, the major effect. 2. Opening of ATP-sensitive potassium channels (KATP channels) and repolarization of the cell. 3. Closing of L-type voltage-dependent calcium channels and inhibition of calcium influx. 4. Inhibition of adenylyl cyclase activity. The first event in adrenaline/noradrenaline signaling in beta cells is the binding of adrenaline or noradrenaline to alpha-2 adrenergic receptors, which are G-protein coupled receptors. Binding activates the alpha subunits in heterotrimeric Gi and Go complexes to exchange GDP for GTP, forming the active G alpha:GTP complex. Experiments using specific antibodies against the alpha subunits in mice show that Gi alpha-1, Gi alpha-2, and Go alpha-2 are responsible for adrenergic effects. The exact beta and gamma subunits of the heterotrimeric G-proteins are unknown. After activation by GTP, the heterotrimeric complex dissociates into the G alpha:GTP complex and the beta:gamma complex. The G alpha:GTP complex causes the inhibition of exocytosis by an unknown mechanism that involves protein acylation. This is responsible for most of the observed inhibition of insulin secretion. Additionally, the G alpha:GTP complex activates (opens) KATP channels, allowing the cell to repolarize. The beta:gamma complex inhibits (closes) voltage-dependent calcium channels, reducing the intracellular calcium concentration, and inhibits adenylyl cyclase, reducing the intracellular cAMP concentration. More... | |
| REACT_15380 | diabetes pathways | ||
| REACT_18325 | regulation of_insulin_secretion | Pancreatic beta cells integrate signals from several metabol...... Pancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or inhibit the amount of insulin secreted in response to glucose. Factors which increase insulin secretion include the incretin hormones Glucose-dependent insulinotropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1), acetylcholine, and fatty acids. Factors which inhibit insulin secretion include adrenaline and noradrenaline. More... | |
| REACT_18266 | axon guidance | Axon guidance / axon pathfinding is the process by which neu...... Axon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, which senses the guidance cues in the environment through guidance cue receptors and responds by undergoing cytoskeletal changes that determine the direction of axon growth. Guidance cues present in the surrounding environment provide the necessary directional information for the trip. These extrinsic cues have been divided into attractive or repulsive signals that tell the growth cone where and where not to grow. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules and their receptors that guide axons. These include netrins, Slits, semaphorins, and ephrins, and their cognate receptors, DCC and or uncoordinated-5 (UNC5), roundabouts (Robo), neuropilin and Eph. In addition, many other classes of adhesion molecules are also used by growth cones to navigate properly which include NCAM and L1CAM. More... | |
| REACT_18274 | regulation of_insulin_secretion_by_glucagon_like_peptide_1 | Glucagon-like Peptide-1 (GLP-1) is secreted by L-cells in th...... Glucagon-like Peptide-1 (GLP-1) is secreted by L-cells in the intestine in response to glucose and fatty acids. GLP-1 circulates to the beta cells of the pancreas where it binds a G-protein coupled receptor, GLP-1R, on the plasma membrane. The binding activates the heterotrimeric G-protein G(s), causing the alpha subunit of G(s) to exchange GDP for GTP and dissociate from the beta and gamma subunits. The activated G(s) alpha subunit interacts with Adenylyl Cyclase VIII (Adenylate Cyclase VIII, AC VIII) and activates AC VIII to produce cyclic AMP (cAMP). cAMP then has two effects: 1) cAMP activates Protein Kinase A (PKA), and 2) cAMP activates Epac1 and Epac2, two guanyl nucleotide exchange factors. Binding of cAMP to PKA causes the catalytic subunits of PKA to dissociate from the regulatory subunits and become an active kinase. PKA is known to enhance insulin secretion by closing ATP-sensitive potassium channels, closing voltage-gated potassium channels, releasing calcium from the endoplasmic reticulum, and affecting insulin secretory granules. The exact mechanisms for PKA's action are not fully known. After prolonged increases in cAMP, PKA translocates to the nucleus where it regulates the PDX-1 and CREB transcription factors, activating transcription of the insulin gene. cAMP produced by AC VIII also activates Epac1 and Epac2, which catalyze the exchange of GTP for GDP on G-proteins, notably Rap1A.. Rap1A regulates insulin secretory granules and is believed to activate the Raf/MEK/ERK mitogenic pathway leading to proliferation of beta cells. The Epac proteins also interact with RYR calcium channels on the endoplasmic reticulum, the SUR1 subunits of ATP-sensitive potassium channels, and the Piccolo:Rim2 calcium sensor at the plasma membrane. More... | |
| REACT_18312 | ncam1 interactions | The neural cell adhesion molecule, NCAM1 is generally consid...... The neural cell adhesion molecule, NCAM1 is generally considered as a cell adhesion mediator, but it is also considered to be a signal transducing receptor molecule. NCAM1 is involved in multiple cis- and trans-homophilic interactions. It is also involved in several heterophilic interactions with a broad range of other molecules, thereby modulating diverse biological phenomena including cellular adhesion, migration, proliferation, differentiation, survival and synaptic plasticity. More... | |
CACNA1C related interactors from protein-protein interaction data in HPRD (count: 8)
| Gene | Interactor | Interactor in MK4MDD? | Experiment Type | PMID | |
|---|---|---|---|---|---|
| CACNA1C | CABP1 | No | in vitro;in vivo | 15140941 | |
| CACNA1C | GNB1 | No | yeast 2-hybrid | 15953418 | |
| CACNA1C | SRI | No | in vitro | 9668070 | |
| CACNA1C | RIMS1 | No | in vitro | 11438519 | |
| CACNA1C | CACNB3 | No | in vitro | 15170217 | |
| CACNA1C | RYR2 | Yes | in vitro | 11576544 | |
| CACNA1C | PRKACA | No | in vitro;in vivo | 8612821 , 9247274 , 8664319 | |
| CACNA1C | PPM1A | Yes | in vitro;in vivo | 15728831 |