Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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inositol 1,4,5-trisphosphate receptor type 1(ITPR1) inositol 1,4,5-trisphosphate receptor type 1(ITPR1) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3p26-p25,
ENSEMBL_GENE_ID ENSG00000150995,
GENERIF_SUMMARY results indicate the InsP3R channel does not significantly differ functionally in terms of Ca2+ release rates between isoforms, involved in the activation of store-mediated Ca(2+) entry by coupling to Trp1 in normal human platelets, study demonstrates the functional presence of type I InsP(3)R-operated Ca(2+) channels in human oocytes and further suggests an active role of InsP(3) in triggering the Ca(2+) rise and secondary activation phenomena at fertilization, IP3R interaction with TRPC1 is signaled by Rho activation at the plasma membrane of endothelial cells, and Ca2+ entry is triggered following store depletion, Mutation analysis from two representative affected family members excluded the coding region of the ITPR1 gene from being involved in the pathogenesis of spinocerebellar ataxia type 15., These results indicate that inositol 1,4,5-trisphosphate receptors may be a specific target for cdc2/CyB during cell cycle progression., differential expression of the IP(3)R subtype is critical for various forms of Ca(2+) signaling, and, particularly, IP(3)R1 and IP(3)R3 have opposite roles in generating Ca(2+) oscillations, one function of tyrosine phosphorylation of IP3R1-Y353 is to enhance Ca2+ signaling in lymphocytes, The causative gene for some Japanese spinocerebellar ataxia is allelic to SCA15., Altered mRNA expression is associated with prostate cancer recurrence., PLSCR1 binds to the promoter region of the IP3R1 gene to enhance its expression, PC2 and IP3R functionally interact and modulate intracellular Ca2+ signaling, Cdc2/cyclin B1 interacts with and modulates inositol 1,4,5-trisphosphate receptor (type 1) functions., ATP binding specifically to the ATPC site in S2- InsP3R-1 controls the susceptibility of the receptor to protein kinase A-mediated phosphorylation, CIB1 is a ubiquitously expressed activating and inhibiting protein ligand of the InsP(3)R, Signaling via IP(3)R may therefore be sufficient to drive essential DC Ca(2+) signaling processes in the absence of RyR expression or function., We show that Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on phospholipase C-gamma1 (PLC-gamma1) activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels., These results strongly suggest that IP(3)R exerts a major role in the physiological control of autophagy., Antibodies in Sjogren's syndrome recognized residues 224-604 of the core protein IP(3)R1., Heterozygous deletion of the 5' part of the ITPR1 gene, encompassing exons 1-10, 1-40, and 1-44 in three studied families, underlies spinocerebellar ataxia 15 in humans., Nitric oxide-induced motility in osteoclasts requires regulated Ca(2+) release, which activates mu-calpain. This occurs via the Ins(1,4,5)P(3)R1., Our data provide evidence that haploinsufficiency of ITPR1 alone causes SCA16 and SCA15., IP(3)R1 binds to the scaffolding protein linker of activated T cells and colocalizes with the T cell receptor during activation, resulting in persistent phosphorylation of IP(3)R1 at Tyr353., Ankyrin B modulates the function of Na,K-ATPase/inositol 1,4,5-trisphosphate receptor signaling microdomain, inositol 1,4,5-trisphosphate receptors are required for tumor-mediated lymphocyte apoptosis, Our results strongly confirm that ITPR1 is the causative gene for SCA15 and suggest that we need to investigate the point mutation in ITPR1 in the patients with autosomal dominant cerebellar ataxia and tremor., The interaction of Bcl-2 with IP3Rs contributes to the regulation of proapoptotic Ca2+ signals by Bcl-2., these results indicate the involvement of the InsP3R-mediated pathway in the modulation of depressive conditions and may be useful for the development of new therapeutical strategies for the treatment of mood disorders, 80K-H is a novel regulator of IP3R1 activity, and it may contribute to neuronal functions., Insulin promotes the interaction of Hsp90 with the IP(3)R to dampen its Ca(2+) release activity by a complex mechanism involving mammalian target of rapamycin and the Src kinase., These results identify IP(3)R as a new regulator of the Beclin 1 complex that may bridge signals converging on the ER and initial phagophore formation., a key pathway by which TNF-alpha in a neuronal environment modulates IP(3)R expression and intracellular Ca(2+) homeostasis, PC1 inhibits Ca(2+) release, perhaps opposing the effect of PC2, which facilitates Ca(2+) release through the IP(3)R., Increased InsP(3)R expression may be a general phenomenon that underlies Ca(2+) changes during hypertrophy., ITPR1-reduced expression in blood may be a useful marker to identify SCA15 patients harboring genomic deletions and possibly point mutations causing reduction of mRNA level., In Duchenne muscular dystrophy biopsies, all fibers display a homogeneous IP(3)R2 label, whereas 24 +/- 7% of type II fibers have lost the IP(3)R1 label., These findings identify inositol (1,4,5)-triphosphate receptor as a new determinant in HIV-1 trafficking during Gag assembly and introduce IP3R-regulated Ca(2+) signaling as a potential novel cofactor in viral particle release., results indicate that point mutations in ITPR1 are at best a rare cause of ADCA III., the heterogeneous expression of the IP3R1-nls-lacZ transgene in Purkinje cell subsets may be useful as a molecular indicator of functional units, such as microcomplexes, of the cerebellar circuitry., SCA15 is a slowly or nonprogressive pure cerebellar ataxia, which appears to be caused by a loss of ITPR1 function and a reduction in the translated protein, Coupled chromogranins change the IP(3)R/Ca(2+) channels to a more ordered, release-ready state, whereby making the IP(3)R/Ca(2+) channels significantly more sensitive to IP(3)., all IP(3)R types are subject to ubiquitination at approximately the same locations and that, independent of cell type, IP(3)Rs are modified by monoubiquitin and Lys-48- and Lys-63-linked ubiquitin chains, although in differing proportions, Screening for ITPR1 deletions should be considered in patients with slowly progressive spinocerebellar ataxia , vermal cerebellar atrophy and prominent tremor after excluding common SCA repeat expansions., A novel SCA15 Italian family is affected with autosomal dominant cerebellar ataxia; two of them have mild intermittent involuntary movements in association with clinical hallmarks of SCA15 (gait ataxia, balance impairment, and dysarthria)., KRAP is involved in the proper regulation of IP3R-mediated Ca2+ release., In this series, ITPR1 deletions were rare and accounted for approximately 1% of all autosomal dominant cerebellar ataxias., Constitutive CREB phosphorylation by exaggerated InsP(3)R Ca(2+) signaling in familial Alzheimer's disease (FAD) PS-expressing cells may represent a signaling pathway involved in the pathogenesis of AD., The potential of point mutations in ITPR1 to cause SCA15., Authors conclude that ITPR1 gene deletions are much rarer in Japan than in Europe., Type 1 inositol-1,4,5-trisphosphate receptor is a late substrate of caspases during apoptosis., Thus, rather than involving the 5-HT3-dependent pathway, the negative effect of ondansetron on platelet aggregation is instead manifested through the attenuation of agonist-induced IP3 production and MAPK (p38 and ERK2)., Glutathionylation may represent a fundamental mechanism for regulating IP3R activity during physiological redox signalling and during pathologicalical oxidative stress, These combined findings implicate IP3-gated Ca(2+) as a key regulator of TDP-43 nucleoplasmic shuttling and proteostasis and suggest pharmacologic inhibition of ITPR1 as a strategy to combat TDP-43-induced neurodegeneration in vivo., we propose a novel regulatory mechanism of IP3R1 activity by type III intermediate filament vimentin, study demonstrates that alteration of ITPR1 function cause a distinct congenital nonprogressive ataxia; highlighting heterogeneity associated with ITPR1 gene and a role of the ITPR1-related pathway in the development and maintenance of the cerebellum., The inositol 1,4,5-trisphosphate receptors are not degradated until very late in apoptosis, and this is despite robust calpain activation as determined by alpha-fodrin cleavage in the presence of Z-VAD-FMK., results indicate that in some congenital myopathy patients RYR1 deficiency concomitantly alters the expression pattern of several proteins involved in calcium homeostasis and that this may influence the manifestation of these diseases, These results suggest an involvement of hydrogen sulfide in both IP3-induced calcium signalling and induction of apoptosis, possibly through the activation of endoplasmic reticulum stress., Studies indicate that three subtypes of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R1, -2, and -3) are assembled to form homo- and heterotetrameric channels that mediate Ca(2+) release from intracellular stores., The Galphaq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias., CHERP and ALG-2 participate in regulation of alternative splicing of IP3R1 pre-mRNA and provide new insights into post-transcriptional regulation of splicing variants in Ca(2+) signaling pathways., Activation of GalR2 leads to elevation of intracellular Ca(2+) due to Ca(2+) efflux from endoplasmic reticulum through IP3R sequentially opening BK alpha channels., These data indicate that imiquimod triggers IP3 receptor-dependent Ca(2+) signaling independently of TLR7., a pleiotropic enzyme transglutaminase type 2 targets the allosteric coupling domain of IP3R type 1 (IP3R1) and negatively regulates IP3R1-mediated calcium signaling and autophagy by locking the subunit configurations., Both ITPR1 and Beclin-1 silencing in 786-0 cells inhibited NK-induced autophagy., IP3R palmitoylation is a critical regulator of Ca(2+) flux in immune cells and a previously unidentified DHHC/Selk complex is responsible for this process., cAMP is delivered directly and at saturating concentrations to its targets, mediate sensitization of IP3R and a more slowly developing inhibition of IP3 accumulation., Ca(2+) release mediated by IP3R1 is an essential mechanism during the early steps of myoblast differentiation., ITPR1 has a role in the pathogenesis of autoimmune cerebellitis in cerebellar ataxia., hyperphosphorylation contributes to prostate cancer cell resistance to androgen deprivation, ITPR1 missense mutations cause infantile-onset cerebellar ataxia., Studies indicate that the ryanodine receptors (RyRs, we identified two in our cohort with a diagnosis of ataxic cerebral palsy who were found to have a de novo mutation in ITPR1, the ability to generate tetramers with defined wild type and mutant subunits will be useful in probing fundamental questions relating to IP3Rs (R1, R2, R3) structure and function., IT plays an essential role in the development of drug dependence.,
OFFICIAL_GENE_SYMBOL ITPR1,
OMIM_DISEASE Spinocerebellar ataxia 29, congenital nonprogressive, Spinocerebellar ataxia 15,
SP_COMMENT alternative products:There is a combination of three alternatively spliced domains at site SI, SIII and site SII (A and C). Experimental confirmation may be lacking for some isoforms, disease:Defects in ITPR1 are the cause of spinocerebellar ataxia type 15 (SCA15) (SCA15) [MIM:606658]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA15 is an autosomal dominant cerebellar ataxia (ADCA). It is very slow progressing form with a wide range of onset, ranging from childhood to adult. Most patients remain ambulatory., domain:The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region., function:Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate., miscellaneous:Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor., PTM:Phosphorylated by cAMP kinase. Phosphorylation prevents the ligand-induced opening of the calcium channels., PTM:Phosphorylated on tyrosine residues., similarity:Belongs to the InsP3 receptor family., similarity:Contains 5 MIR domains., subunit:Homotetramer. Interacts with TRPC4. The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium-dependent manner which results in the inhibition the calcium channel activity. The strength of this interaction inversely correlates with calcium concentration. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with AHCYL1 (By similarity). Interacts with MRVI1., tissue specificity:Widely expressed.,
inositol 1,4,5-trisphosphate receptor type 2(ITPR2) inositol 1,4,5-trisphosphate receptor type 2(ITPR2) Related Genes Homo sapiens
CHROMOSOME 12,
CYTOBAND 12p11,
ENSEMBL_GENE_ID ENSG00000123104,
GENERIF_SUMMARY Antibodies are detected most frequently in rheumatoid arthritis., Genetic variation is susceptibility factor for amyotrophic lateral sclerosis(ALS). Involved in glutamate-mediated neurotransmission, is one of main regulators of intracellular calcium concentrations, and has important role in apoptosis., Provide evidence for a functional role of the de novo coupling between hTRPC1 and IP3RII in the activation of store operated calcium entry in platelets., Parathyroid hormone communicates with IP(3)R via "cAMP junctions" that allow local delivery of a supramaximal concentration of cAMP to IP(3)R, directly increasing their sensitivity to IP(3)., The result of this study suggested that ITPR2 that do not modulate the risk for SALS in the German population., Elevated InsP(3)R2 expression was also detected in hearts from human patients with heart failure after ischemic dilated cardiomyopathy, as well as in aortic-banded hypertrophic mouse hearts., Dystrophic (RCDMD) human muscle cells show 5-fold overexpression of IP(3)R2 and down-regulation of IP(3)R3 compared with normal human muscle cells., The knock down of IP3R-2 significantly reduced the intracellular Ca2+ response and this reduced Ca2+ response did not affect the activation of CREB but significantly decreased the activation of NFAT., ITPR2 is a functional target gene of the BACH1 transcription factor according to ChIP-seq and knockdown analysis in HEK 293 cells., Functional IP3R2s are expressed in the mouse sinoatrial node and could serve as an additional divalent calcium ion-dependent mechanism in modulating cardiac pacemaker., These data suggest that ER Ca(2+) released by IP(3) receptors may be detrimental in amyotrophic lateral sclerosis and that motor neurons are vulnerable to impaired Ca(2+) metabolism., These results suggest an involvement of hydrogen sulfide in both IP3-induced calcium signalling and induction of apoptosis, possibly through the activation of endoplasmic reticulum stress., Studies indicate that three subtypes of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R1, -2, and -3) are assembled to form homo- and heterotetrameric channels that mediate Ca(2+) release from intracellular stores., The Galphaq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias., ITPR2 and hypertrophy specific gene expression is regulated, in part, by a positive feedback regulation between InsP3R2 and calcineurin-NFATc signaling pathways., results show a functional role of calcium release by the ITPR2 channel and its subsequent accumulation in the mitochondria, A genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese., Loss of InsP3R2-mediated calcium release causes isolated anhidrosis in humans., Disrupting IP3R/Bcl-2 interaction therefore leads in those cells to increased Ca(2) release and apoptosis. Intriguingly, IP3R2 is not only implicated in apoptosis but also in the induction of senescence, another tumour-suppressive mechanism., High expression of inositol 1,4,5-trisphosphate receptor, type 2 is associated with acute myeloid leukemia., Studies indicate that the ryanodine receptors (RyRs, the ability to generate tetramers with defined wild type and mutant subunits will be useful in probing fundamental questions relating to IP3Rs (R1, R2, R3) structure and function., Data suggest miR-1290 as the new oncomiR involved in laryngeal squamous cell carcinoma pathogenesis probably through downregulation of its target genes MAF and ITPR2.,
OFFICIAL_GENE_SYMBOL ITPR2,
OMIM_DISEASE Anhidrosis, isolated, with normal sweat glands,
SP_COMMENT domain:The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region., function:Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium., miscellaneous:Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor., PTM:Phosphorylated on tyrosine residues., similarity:Belongs to the InsP3 receptor family., similarity:Contains 5 MIR domains., subunit:Homotetramer., tissue specificity:The short isoform is found in skeletal muscle and heart.,
inositol 1,4,5-trisphosphate receptor type 3(ITPR3) inositol 1,4,5-trisphosphate receptor type 3(ITPR3) Related Genes Homo sapiens
CHROMOSOME 6,
CYTOBAND 6p21,
ENSEMBL_GENE_ID ENSG00000096433,
GENERIF_SUMMARY IP3R3 may be a prerequisite for secretion of an enzyme, such as protease, in gastric cancer cells; results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination, differential expression of the IP(3)R subtype is critical for various forms of Ca(2+) signaling, and, particularly, IP(3)R1 and IP(3)R3 have opposite roles in generating Ca(2+) oscillations, The estimated population-attributable risk of 21.6% suggests that variation within ITPR3 reflects an important contribution to type 1 diabetes in Sweden., Anti-IP(3)R1 antibodies were present in 48.6% of primary Sjogren's syndrome and in 3.0% of normal healthy subjects., IP3R3 is present in the paranodal regions of the nodes in the sciatic nerve., A functional single nucleotide polymorphism in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus, the ankyrin-binding site is located on the cytoplasmic face of the InsP(3) receptor, thus validating the feasibility of in vivo ankyrin-InsP(3) receptor interactions., The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II., In this review, by sensing sequential binding of IP3 and calcium ions, the IP3 receptor acts as a coincidence detector that associates parallel fiber inputs with climbing fiber inputs., sigma-1R overexpression drives sigma agonist-independent dissociation of ANK 220 from IP3R-3, resulting in activation, the agonist-induced clustering of IP(3)R is triggered by IP(3) binding, rather than [Ca(2+)](i) elevation., May play a role in calcium-dependent nuclear processes., IP3-mediated sensitization requires IP3 receptor binding to a TRPV4 C-terminal domain that overlaps with a previously described calmodulin-binding site, Inability of the T-cell receptors in TCR transgenic mice to trigger calcium mobilization may be due to the insufficient level of inositol 1,4,5-triphosphate receptor (IP3) type 3 to initiate the release of calcium from intracellular stores., Caveolin-1 scaffold domain interacts with TRPC1 and IP3R3 to regulate Ca2+ store release-induced Ca2+ entry in endothelial cells., Results demonstrate the importance of the InsP3 receptor-mutant huntingtin protein association for the pathogenesis of Huntington's disease and as a potential therapeutic target for Huntington's disease., Data show that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor on the endoplasmic reticulum., Findings suggest IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma., Dystrophic (RCDMD) human muscle cells show 5-fold overexpression of IP(3)R2 and down-regulation of IP(3)R3 compared with normal human muscle cells., results of this study suggest that the rs2229634 SNP in the ITPR3 gene is associated with the risk of coronary artery aneurysm formation in Taiwanese Kawasaki disease patients, inositol 145-triphosphate receptor type 3 becomes expressed in colon cancer, and its expression level is directly related to aggressiveness of the tumor, the critical region of KRAP protein for the regulation of IP(3)R was determined., Ins(1,4,5)P3R-mediated Ca2+ signaling was critical for starvation-induced autophagy stimulation., The study provides biochemical evidence of the interaction between FKBP12 and RYR1, RYR3 and IP3R., The presence of isoform III of inositol 1,4,5-trisphosphate receptor is the key point of Akt activity on calcium-mediated apoptosis., in human pulmonary fibroblasts, PDGF acts through IP3-induced Ca(2+)-release to trigger Ca(2+) waves, which in turn modulate gene expression of several matrix proteins., Studies indicate that three subtypes of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R1, -2, and -3) are assembled to form homo- and heterotetrameric channels that mediate Ca(2+) release from intracellular stores., The Galphaq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias., A molecular and functional link between BKCa channel and IP3R3 in cancer cells as an important mechanism for tumor cell proliferation., It mediate calcium release from intracellular calcium stores such as the ER into the cytoplasm. (review), Physiologically relevant reactive oxygen species controls cytoplasmic and mitochondrial calcium transport through IP3 receptors., miR-506 is a regulator of InsP3R3 expression and InsP3R3-mediated Ca2+ signaling and secretion., The transcription factor NRF2 binds to the promoter of ITPR3 to inhibit its expression in cholangiocytes, leading to reduced calcium signaling and bile duct secretion., Studies indicate that the ryanodine receptors (RyRs, the ability to generate tetramers with defined wild type and mutant subunits will be useful in probing fundamental questions relating to IP3Rs (R1, R2, R3) structure and function.,
OFFICIAL_GENE_SYMBOL ITPR3,
OMIM_DISEASE Diabetes, type 1, susceptibility to,
SP_COMMENT domain:The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region., function:Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium., PTM:Phosphorylated on tyrosine residues., similarity:Belongs to the InsP3 receptor family., similarity:Contains 5 MIR domains., subunit:Homotetramer. Interacts with OPRS1, TRPC1, TRPC3 and TRPC4., tissue specificity:Expressed in intestinal crypt and villus epithelial cells.,