Gene Report

Basic Information

Approved Symbol	ITPR1
Approved Name	inositol 1,4,5-trisphosphate receptor, type 1
Previous Symbol	SCA15, SCA16
Previous Name	spinocerebellar ataxia 15, "spinocerebellar ataxia 16"
Symbol Alias	Insp3r1, IP3R1
Location	3p26.1
Position	chr3:4535032-4889524 (+)
External Links	Entrez Gene: 3708 Ensembl: ENSG00000150995 UCSC: uc021wsi.1 HGNC ID: 6180
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin; SNP mapped

Positive relationships between ITPR1 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
ITPR1	Sequeira, 2007	patients and normal controls		Selected differentially expressed genes in hippocampus Selected differentially expressed genes in hippocampus

Positive relationships between ITPR1 and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
ITPR1		Hippocampus(hippocampus)	brain morphology and function	Sequeira, 2007	patients and normal controls		Selected differentially expressed genes in hippocampus Selected differentially expressed genes in hippocampus

Positive relationship network of ITPR1 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

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
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 ITPR1 and MDD (count: 0)

Negative relationships between ITPR1 and other components at different levels (count: 0)

ITPR1 related SNPs in MK4MDD (count: 1)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs9311395	chr3:4741821(Forward)	intron_variant	1(0/1)

ITPR1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Inositol 1,4,5-trisphosphate receptor type 1	Q14643	0(0/0)	Gene mapped

ITPR1 related GO terms (count: 26)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	biological process	ISS
GO:0048011	nerve growth factor receptor signaling pathway	biological process	TAS
GO:0006816	calcium ion transport	biological process	NAS[7852357]
GO:0035091	phosphatidylinositol binding	molecular function	ISS
GO:0007173	epidermal growth factor receptor signaling pathway	biological process	TAS
GO:0005783	endoplasmic reticulum	cellular component	NAS[8648241]
GO:0031095	platelet dense tubular network membrane	cellular component	TAS
GO:0050796	regulation of insulin secretion	biological process	TAS
GO:0008543	fibroblast growth factor receptor signaling pathway	biological process	TAS
GO:0007596	blood coagulation	biological process	TAS
GO:0016021	integral to membrane	cellular component	IEA
GO:0001666	response to hypoxia	biological process	IDA[19120137]
GO:0015085	calcium ion transmembrane transporter activity	molecular function	TAS[7500840]
GO:0005515	protein binding	molecular function	IPI
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0007202	activation of phospholipase C activity	biological process	TAS
GO:0051209	release of sequestered calcium ion into cytosol	biological process	ISS
GO:0006112	energy reserve metabolic process	biological process	TAS
GO:0005218	intracellular ligand-gated calcium channel activity	molecular function	ISS
GO:0005220	inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity	molecular function	ISS; TAS[8648241]
GO:0048016	inositol phosphate-mediated signaling	biological process	ISS; TAS[8648241]
GO:0031094	platelet dense tubular network	cellular component	IDA[10828023]
GO:0005789	endoplasmic reticulum membrane	cellular component	TAS
GO:0031088	platelet dense granule membrane	cellular component	IDA[10828023]
GO:0030168	platelet activation	biological process	TAS
GO:0007165	signal transduction	biological process	NAS[8648241]; TAS

ITPR1 related KEGG pathways (count: 10)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
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...
hsa04070	phosphatidylinositol signaling_system	Phosphatidylinositol signaling system
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...
hsa04730	long term_depression	Long-term depression	Cerebellar long-term depression (LTD), thought to be a molec...... Cerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and Purkinje cells (PCs) induced by the conjunctive activation of PFs and climbing fiber (CF). Multiple signal transduction pathways have been shown to be involved in this process. Activation of PFs terminating on spines in dendritic branchlets leads to glutamate release and activation of both AMPA and mGluRs. Activation of CFs, which make multiple synaptic contacts on proximal dendrites, also via AMPA receptors, opens voltage-gated calcium channels (VGCCs) and causes a generalized influx of calcium. These cellular signals, generated from two different synaptic origins, trigger a cascade of events culminating in a phosphorylation-dependent, long-term reduction in AMPA receptor sensitivity at the PF-PC synapse. This may take place either through receptor internalization and/or through receptor desensitization. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05016	huntingtons disease	Huntington's disease	Huntington disease (HD) is an autosomal-dominant neurodegene...... Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2+ signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NR2B/NR1 NMDAR activity, and destabilizing mitochondrial Ca2+ handling. As a result, stimulation of glutamate receptors leads to supranormal Ca2+ responses in HD MSN and mitochondrial Ca2+ overload. The mHtt translocates to the nucleus, where it forms intranuclear inclusions, though they are not primarily responsible for toxicity. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction. More...
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...
hsa04540	gap junction	Gap junction	Gap junctions contain intercellular channels that allow dire...... Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation. 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...
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...

ITPR1 related BioCarta pathways (count: 0)

ITPR1 related Reactome pathways (count: 16)

ID	Name	Description
Gene mapped Reactome pathways
REACT_19375	regulation of_insulin_secretion_by_free_fatty_acids	Free fatty acids augment the glucose-triggered secretion of ...... Free fatty acids augment the glucose-triggered secretion of insulin. The augmentation is believed to be due to the additive effects of the activation of the free fatty acid receptor 1 (FFAR1 or GPR40) and the metabolism of free fatty acids within the pancreatic beta cell. This module describes each pathway. More...
REACT_604	hemostasis	Two principal mechanisms limit blood loss after vascular inj...... Two principal mechanisms limit blood loss after vascular injury. Initially, platelets are activated, adhere to the site of the injury, and aggregate into a plug that limits blood loss. Proteins and small molecules released from activated platelets stimulate the plug formation process, and fibrinogen from the plasma forms bridges between activated platelets. These events allow the initiation of the clotting cascade, the second mechanism to limit blood loss. Negatively charged phospholipids exposed on cell surfaces at the site of injury and on activated platelets interact with tissue factor, setting off a cascade of reactions leading to generation of fibrin and the formation of an insoluble fibrin clot that strengthens the platelet plug. More...
REACT_15380	diabetes pathways
REACT_15426	plc beta_mediated_events	The phospholipase C (PLC) family of enzymes is both diverse ...... The phospholipase C (PLC) family of enzymes is both diverse and complex. The isoforms beta, gamma and delta (each have subtypes) make up the members of this family. PLC hydrolyzes phosphatidylinositol bisphosphate (PIP2) into two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores while DAG activates protein kinase C isoforms which are involved in regulatory functions. More...
REACT_19184	downstream events_in_gpcr_signaling	G protein-coupled receptors. The beta:gamma G-protein dimer ...... G protein-coupled receptors. The beta:gamma G-protein dimer is also involved in downstream signaling , and some receptors form part of metastable complexes of receptor and accessory proteins such as the arrestins. GPCRs are involved in many diverse signaling events , using a variety of pathways that include modulation of adenylyl cyclase, phospholipase C, the mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK) c-Jun-NH2-terminal kinase (JNK) and p38 MAPK. More...
REACT_12079	plc gamma1_signalling	The activation of phosphlipase C-gamma (PLC-gamma) and subse...... The activation of phosphlipase C-gamma (PLC-gamma) and subsequent mobilization of calcium from intracellular stores are essential for neurotrophin secretion. PLC-gamma is activated through the phosphorylation by TrkA receptor kinase and this form hydrolyses PIP2 to generate inositol tris-phosphate (IP3) and diacylglycerol (DAG). IP3 promotes the release of Ca2+ from internal stores and this results in activation of enzymes such as protein kinase C and Ca2+ calmodulin-regulated protein kinases. More...
REACT_12056	trka signalling_from_the_plasma_membrane	Trk receptors signal from the plasma membrane and from intra...... Trk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes is slower but long lasting. Signalling from the plasma membrane is annotated here. TRK signalling leads to proliferation in some cell types and neuronal differentiation in others. Proliferation is the likely outcome of short term signalling, as observed following stimulation of EGFR (EGF receptor). Long term signalling via TRK receptors, instead, was clearly shown to be required for neuronal differentiation in response to neurotrophins. More...
REACT_18283	g alpha_q_signalling_events	The classic signalling route for G alpha (q) is activation o...... The classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gq participates in many other signalling events including direct interaction with RhoGEFs that stimulate RhoA activity and inhibition of PI3K. Both in vitro and in vivo, the G-protein Gq seems to be the predominant mediator of the activation of platelets. More...
REACT_11061	signalling by_ngf	Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles i...... Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in minute amounts, by a variety of tissues. They signal through two types of receptors: TRK tyrosine kinase receptors (TRKA, TRKB, TRKC), which specifically interact with the different neurotrophins, and p75NTR, which interacts with all neurotrophins. TRK receptors are reported in a variety of tissues in addition to neurons. p75NTRs are also widespread. Neurotrophins and their receptors are synthesized as several different splice variants, which differ in terms of their biological activities. The nerve growth factor (NGF) was the first growth factor to be identified and has served as a model for studying the mechanisms of action of neurotrophins and growth factors. The mechanisms by which NGF generates diverse cellular responses have been studied extensively in the rat pheochromocytoma cell line PC12. When exposed to NGF, PC12 cells exit the cell cycle and differentiate into sympathetic neuron-like cells. Current data show that signalling by the other neurotrophins is similar to NGF signalling. More...
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_20	formation of_platelet_plug	Hemostasis is a physiological response that culminates in th...... Hemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Acute vessel injury results in its constriction to reduce the loss of blood. Under normal conditions vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in character. Under acute vascular trauma vasoconstrictor mechanisms predominate and the endothelium becomes prothrombotic, procoagulatory and proinflammatory in nature. This is achieved by a reduction of endothelial dilating agents: adenosine, NO and prostacyclin; and the direct action of ADP, serotonin and thromboxane on vascular smooth muscle cells to elicit their contraction. The chief trigger for the change in endothelial function that leads to the formation of haemostatic thrombus is the loss of the endothelial cell barrier between blood and ECM components. Circulating platelets identify and discriminate areas of endothelial lesions; here, they adhere to the exposed sub endothelium. Their interaction with the various thrombogenic substrates and locally generated or released agonists results in platelet activation. This process is described as possessing two stages, firstly, adhesion - the initial tethering to a surface, and secondly aggregation - the platelet-platelet cohesion. 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_798	platelet activation	Platelet activation begins with the initial binding of adhes...... Platelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists. Intracellular signaling reactions will then enhance the adhesive and procoagulant properties of tethered platelets or of platelets circulating in the proximity. From the subendothelial adhesive substrates, collagen and possibly vWF are the main inducers of platelet activation. GP VI is the most potent collagen receptor initiating signal generation, an ability derived from its interaction with the FcRI gamma chain. This results in the phosphorylation of the gamma-chain by the non-receptor tyrosine kinases of the Src family. The phosphotyrosine motif is recognized by the SH2 domains of Syk, a tyrosine kinase. This association activates the Syk enzyme, leading to activation. Four PARs are identified, of which PARs 1 ,3 and 4 are substrates for thrombin. PAR 1 is the predominant thrombin receptor, PAR 3 is minimally expressed and PAR 4 is less responsive to thrombin. Platelets do not store PAR1, due to limited protein synthesis, they are capable of responding to thrombin only once. Platelet activation further results in the scramblase-mediated transport of negatively-charged phospholipids to the platelet surface. These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase complex (formed by the activated forms of the blood coagulation factors factor VIII and factor I). More...
REACT_18405	regulation of_insulin_secretion_by_acetylcholine	Acetylcholine released by parasympathetic nerve endings in t...... Acetylcholine released by parasympathetic nerve endings in the pancreas causes a potentiation of insulin release when glucose is present at concentrations greater than about 7 mM. Acetylcholine binds the Muscarinic Acetylcholine Receptor M3 on pancreatic beta cells. The binding has two effects: an increase in permeability of the cell to Na+ ions through an unknown mechanism, and the activation of Phospholipase C beta-1 through a heterotrimeric G protein, G(q). After acetylcholine binds the Muscarinic Acetycholine Receptor M3, the receptor activates the G protein Gq by causing the alpha subunit of Gq to exchange GDP for GTP. Activation of Gq in turn activates Phospholipase C beta-1. Phospholipase C beta-1 hydrolyzes the phosphodiester bond at the third position of phosphoinositol 4,5-bisphosphate, producing diacylglycerols (DAG) and inositol 1,4,5-trisphosphate. DAG remains in the cell membrane and causes Protein Kinase C alpha (PKC alpha) to translocate from the cytosol to the membrane. This results in the activation of PKC alpha which then phosphorylates target proteins on serine and threonine residues. One known target of PKC alpha is Myristoylated Alanine-rich C Kinase Substrate (MARCKS), which is believed to affect vesicle transport and may be responsible for the increased traffic of insulin granules seen in response to acetylcholine. Inositol trisphophate binds a receptor, the IP3 receptor, on calcium stores in the cell (probably the endoplasmic reticulum). The release of calcium into the cytosol stimulates the exocytosis of insulin granules. More...
REACT_2202	effects of_pip2_hydrolysis	Hydrolysis of phosphatidyl inositol-bisphosphate (PIP2) by p...... Hydrolysis of phosphatidyl inositol-bisphosphate (PIP2) by phospholipase C (PLC) produces diacylglycerol (DAG) and inositol triphosphate (IP3). Both are potent second messengers. IP3 diffuses into the cytosol, but as DAG is a hydrophobic lipid it remains within the plasma membrane. IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, while DAG activates the conventional and unconventional protein kinase C (PKC) isoforms, facilitating the translocation of PKC from the cytosol to the plasma membrane. The effects of DAG are mimicked by tumor-promoting phorbol esters. DAG is also a precursor for the biosynthesis of prostaglandins, the endocannabinoid 2-arachidonoylglycerol and an activator of a subfamily of TRP-C (Transient Receptor Potential Canonical) cation channels 3, 6, and 7. More...
REACT_15295	opioid signalling	Opioids are chemical substances similar to opiates, the acti...... Opioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as the enkephalins, the endorphins or the dynorphins. Opioids possess powerful analgesic and sedative effects, and are widely used as pain-killers. Their main side-effect is the rapid establishment of a strong addiction. Opioids receptors are G-protein coupled receptors (GPCR). There are four classes of receptors: mu (MOR), kappa (KOR) and delta (DOR), and the nociceptin receptor (NOP). More...

ITPR1 related interactors from protein-protein interaction data in HPRD (count: 27)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
ITPR1	CCNB1	No	in vitro	16237118
ITPR1	TRPC3	No	in vitro;in vivo	9853757 , 11524429 , 15104175 , 12606542 , 15623527
ITPR1	LYN	No	in vitro	11782428
ITPR1	CA8	No	in vivo;yeast 2-hybrid	12611586
ITPR1	CABP1	No	in vitro;in vivo	14570872 , 14685260 , 12032348
ITPR1	ARHGAP1	No	yeast 2-hybrid	14697242
ITPR1	TRPC4	No	in vitro;yeast 2-hybrid	11163362
ITPR1	BANK1	No	in vivo	11782428
ITPR1	CDK1	No	in vitro;in vivo	14635192 , 16237118
ITPR1	RYR2	Yes	in vivo	12754204
ITPR1	GRM1	Yes	in vivo	9808459
ITPR1	PRKACA	No	in vitro;in vivo	8132598 , 12529267
ITPR1	ITPR3	No	in vivo	7559486
ITPR1	MRVI1	No	in vivo	10724174
ITPR1	ITPRIP	No	in vitro;in vivo;yeast 2-hybrid	16990268
ITPR1	HOMER2	No	in vitro;in vivo	9808459
ITPR1	HOMER1	No	in vitro;in vivo	9808459
ITPR1	HOMER3	No	in vitro;in vivo	9808459
ITPR1	AHCYL1	No	in vitro;in vivo	12525476
ITPR1	FKBP1A	No	yeast 2-hybrid	9346894
ITPR1	PRKG1	No	in vitro;in vivo	8132598
ITPR1	STARD13	No	in vivo;yeast 2-hybrid	14697242
ITPR1	BCL2	No	in vitro	15613488
ITPR1	EPB41L1	No	in vitro;in vivo;yeast 2-hybrid	12676536 , 12444087
ITPR1	FYN	No	in vitro	14761954
ITPR1	RHOA	Yes	in vitro;in vivo	12766172
ITPR1	ERP44	No	in vitro;in vivo	15652484

Gene Report

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways

Gene mapped Reactome pathways