Gene Symbol: Itpr2
Description: inositol 1,4,5-trisphosphate receptor, type 2
Alias: inositol 1,4,5-trisphosphate receptor type 2, IP3 receptor, IP3R 2, inositol 1,4,5-triphosphate receptor 2, inositol 1,4,5-triphosphate receptor, type 2, inositol triphosphate receptor type 2, insP3R2, type 2 InsP3 receptor, type 2 inositol 1,4,5-trisphosphate receptor
Species: rat
Products:     Itpr2

Top Publications

  1. Toews J, Schram V, Weerth S, Mignery G, Russell J. Signaling proteins in the axoglial apparatus of sciatic nerve nodes of Ranvier. Glia. 2007;55:202-13 pubmed
  2. Iwai M, Michikawa T, Bosanac I, Ikura M, Mikoshiba K. Molecular basis of the isoform-specific ligand-binding affinity of inositol 1,4,5-trisphosphate receptors. J Biol Chem. 2007;282:12755-64 pubmed
    ..Moreover, the functional diversity in ligand sensitivity among IP(3)R isoforms originates from at least the structural difference identified on the suppressor domain. ..
  3. Harzheim D, Movassagh M, Foo R, Ritter O, Tashfeen A, Conway S, et al. Increased InsP3Rs in the junctional sarcoplasmic reticulum augment Ca2+ transients and arrhythmias associated with cardiac hypertrophy. Proc Natl Acad Sci U S A. 2009;106:11406-11 pubmed publisher
    ..Our data establish that increased InsP(3)R expression is a general mechanism that underlies remodeling of Ca(2+) signaling during heart disease, and in particular, in triggering ventricular arrhythmia during hypertrophy. ..
  4. Tu H, Wang Z, Nosyreva E, De Smedt H, Bezprozvanny I. Functional characterization of mammalian inositol 1,4,5-trisphosphate receptor isoforms. Biophys J. 2005;88:1046-55 pubmed
    ..Three mammalian InsP3R isoforms--InsP3R type 1 (InsP3R1), InsP3R type 2 (InsP3R2), and InsP3R type 3 (InsP3R3) are expressed in mammals, but the functional differences between the three ..
  5. Sudhof T, Newton C, Archer B, Ushkaryov Y, Mignery G. Structure of a novel InsP3 receptor. EMBO J. 1991;10:3199-206 pubmed
    ..We have now determined the full structure of a second, novel InsP3 receptor which we refer to as type 2 InsP3 receptor as opposed to the cerebellar type 1 InsP3 receptor...
  6. Kruglov E, Ananthanarayanan M, Sousa P, Weerachayaphorn J, Guerra M, Nathanson M. Type 2 inositol trisphosphate receptor gene expression in hepatocytes is regulated by cyclic AMP. Biochem Biophys Res Commun. 2017;486:659-664 pubmed publisher
    ..The findings furthermore suggest that this mechanism is relevant for hormonal regulation of bile secretion. ..
  7. Sliter D, Aguiar M, Gygi S, Wojcikiewicz R. Activated inositol 1,4,5-trisphosphate receptors are modified by homogeneous Lys-48- and Lys-63-linked ubiquitin chains, but only Lys-48-linked chains are required for degradation. J Biol Chem. 2011;286:1074-82 pubmed publisher
  8. Oberdorf J, Webster J, Zhu C, Luo S, Wojcikiewicz R. Down-regulation of types I, II and III inositol 1,4,5-trisphosphate receptors is mediated by the ubiquitin/proteasome pathway. Biochem J. 1999;339 ( Pt 2):453-61 pubmed
    ..In total these data indicate that the ubiquitin/proteasome pathway mediates Ins(1,4, 5)P3-receptor down-regulation and suggest that ubiquitination is stimulated by the binding of Ins(1,4,5)P3 to its receptor. ..
  9. Morel J, Fritz N, Lavie J, Mironneau J. Crucial role of type 2 inositol 1,4,5-trisphosphate receptors for acetylcholine-induced Ca2+ oscillations in vascular myocytes. Arterioscler Thromb Vasc Biol. 2003;23:1567-75 pubmed
    ..By Western blot and immunostaining, we showed that rat portal vein expressed InsP3R1 and InsP3R2 but not InsP3R3, whereas rat ureter expressed InsP3R1 and InsP3R3 but not InsP3R2...

More Information


  1. Kruglov E, Gautam S, Guerra M, Nathanson M. Type 2 inositol 1,4,5-trisphosphate receptor modulates bile salt export pump activity in rat hepatocytes. Hepatology. 2011;54:1790-9 pubmed publisher
    ..Ca(2+) release near the canalicular membrane is mediated by the type II inositol 1,4,5-trisphosphate receptor (InsP3R2), so we investigated the possible role of InsP3R2 in modulating Bsep activity...
  2. Lee B, Bradford P, Laychock S. Characterization of inositol 1,4,5-trisphosphate receptor isoform mRNA expression and regulation in rat pancreatic islets, RINm5F cells and betaHC9 cells. J Mol Endocrinol. 1998;21:31-9 pubmed
  3. Ramos Franco J, Bare D, Caenepeel S, Nani A, Fill M, Mignery G. Single-channel function of recombinant type 2 inositol 1,4, 5-trisphosphate receptor. Biophys J. 2000;79:1388-99 pubmed
    ..The possibility of measuring the function of single recombinant type 2 InsP(3)R is a significant step toward the use of molecular tools to define the determinants of isoform-specific InsP(3)R function and regulation. ..
  4. Jurkovicova D, Sedlakova B, Lacinova L, Kopacek J, Sulova Z, Sedlak J, et al. Hypoxia differently modulates gene expression of inositol 1,4,5-trisphosphate receptors in mouse kidney and HEK 293 cell line. Ann N Y Acad Sci. 2008;1148:421-7 pubmed publisher
    ..The physiological relevance of this observation remains to be determined. ..
  5. Tovey S, Dedos S, Rahman T, Taylor E, Pantazaka E, Taylor C. Regulation of inositol 1,4,5-trisphosphate receptors by cAMP independent of cAMP-dependent protein kinase. J Biol Chem. 2010;285:12979-89 pubmed publisher
    ..We conclude that all three subtypes of IP(3)R are regulated by cAMP independent of PKA. In HEK cells, where IP(3)R2 selectively associates with AC6, G alpha(s) also associates with the AC x IP(3)R signaling junction. ..
  6. Schulman J, Wright F, Kaufmann T, Wojcikiewicz R. The Bcl-2 protein family member Bok binds to the coupling domain of inositol 1,4,5-trisphosphate receptors and protects them from proteolytic cleavage. J Biol Chem. 2013;288:25340-9 pubmed publisher
    ..Thus, Bok may govern IP3R cleavage and activity during apoptosis. ..
  7. Sankar N, DeTombe P, Mignery G. Calcineurin-NFATc regulates type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2) expression during cardiac remodeling. J Biol Chem. 2014;289:6188-98 pubmed publisher
    In heart, the type 2 inositol 1,4,5-triphosphate receptor (InsP3R2) is the predominant isoform expressed and is localized in the nuclear membrane of ventricular myocytes...
  8. Dyer J, Michelangeli F. Inositol 1,4,5-trisphosphate receptor isoforms show similar Ca2+ release kinetics. Cell Calcium. 2001;30:245-50 pubmed
    ..The temporal and spatial features of intracellular Ca2+ signals are thus probably achieved through InsP3R isoform-specific regulation or localization rather than their intrinsic Ca2+ efflux properties. ..
  9. Canossa M, Gartner A, Campana G, Inagaki N, Thoenen H. Regulated secretion of neurotrophins by metabotropic glutamate group I (mGluRI) and Trk receptor activation is mediated via phospholipase C signalling pathways. EMBO J. 2001;20:1640-50 pubmed
    ..Thus, PLC-mediated signal transduction pathways are the common mechanisms for both Trk- and mGluRI-mediated NT secretion. ..
  10. Mery L, Magnino F, Schmidt K, Krause K, Dufour J. Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors. FEBS Lett. 2001;487:377-83 pubmed
    ..Thus, we describe a novel interaction between Trp proteins and InsP3R and we provide evidence suggesting that the formation of hTrp4-InsP3R complexes may be regulated by alternative splicing. ..
  11. Kajimoto K, Daikoku T, Yamazaki N, Terada H, Shinohara Y. Expression profiles of three isoforms of inositol 1,4,5-trisphosphate receptor in brown adipose tissue of the rat. Biochem Pharmacol. 2003;65:995-8 pubmed
    ..However, different from the results of Northern analysis, the expression levels of types 1 and 2 isoforms of IP(3) receptor protein in BAT were not influenced by exposure of the animals to the cold. ..
  12. Holtzclaw L, Pandhit S, Bare D, Mignery G, Russell J. Astrocytes in adult rat brain express type 2 inositol 1,4,5-trisphosphate receptors. Glia. 2002;39:69-84 pubmed
    ..Furthermore, the anatomical arrangement of the terminal astrocytic branches containing IP(3)R2 ensheathing synapses is ideal for supporting glial monitoring of neuronal activity. ..
  13. Gerasimenko J, Lur G, Ferdek P, Sherwood M, Ebisui E, Tepikin A, et al. Calmodulin protects against alcohol-induced pancreatic trypsinogen activation elicited via Ca2+ release through IP3 receptors. Proc Natl Acad Sci U S A. 2011;108:5873-8 pubmed publisher
    ..The inositol trisphosphate receptors, required for normal pancreatic stimulus-secretion coupling, are also responsible for the toxic ethanol action. Calmodulin protects by reducing calcium release sensitivity. ..
  14. Fissore R, Longo F, Anderson E, Parys J, Ducibella T. Differential distribution of inositol trisphosphate receptor isoforms in mouse oocytes. Biol Reprod. 1999;60:49-57 pubmed
    ..Types 1 and 2 isoforms were also present in granulosa cells. ..
  15. Wong A, Grubb D, Cooley N, Luo J, Woodcock E. Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors. J Mol Cell Cardiol. 2013;54:19-24 pubmed publisher
    ..These data provide evidence that Ins(1,4,5)P(3) and IP(3)-R act as inhibitors of autophagic responses in cardiomyocytes. By suppressing autophagy, IP(3)-R may contribute to cardiac pathology. ..
  16. Drawnel F, Wachten D, Molkentin J, Maillet M, Aronsen J, Swift F, et al. Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and cardiac hypertrophy. J Cell Biol. 2012;199:783-98 pubmed publisher
    ..Consequently, IICR can be considered as both an initiating event and a driving force for pathological remodeling. ..
  17. De Smedt H, Missiaen L, Parys J, Bootman M, Mertens L, van den Bosch L, et al. Determination of relative amounts of inositol trisphosphate receptor mRNA isoforms by ratio polymerase chain reaction. J Biol Chem. 1994;269:21691-8 pubmed
    ..4% of the total InsP3R mRNA. InsP3-induced Ca2+ release in permeabilized C3H10T1/2 cells was regulated by luminal and cytosolic Ca2+, stimulated by thimerosal, and inhibited by caffeine. ..
  18. van Es M, Van Vught P, Blauw H, Franke L, Saris C, Andersen P, et al. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol. 2007;6:869-77 pubmed
    ..A genetic variant in the inositol 1,4,5-triphosphate receptor 2 gene (ITPR2) was associated with ALS (p=0.012 after Bonferroni correction)...
  19. Lencesova L, Ondrias K, Micutkova L, Filipenko M, Kvetnansky R, Krizanova O. Immobilization stress elevates IP(3) receptor mRNA in adult rat hearts in a glucocorticoid-dependent manner. FEBS Lett. 2002;531:432-6 pubmed
  20. Yokoyama K, Su Ih I, Tezuka T, Yasuda T, Mikoshiba K, Tarakhovsky A, et al. BANK regulates BCR-induced calcium mobilization by promoting tyrosine phosphorylation of IP(3) receptor. EMBO J. 2002;21:83-92 pubmed
    ..Because BANK expression is confined to functional BCR-expressing B cells, BANK-mediated calcium mobilization may be specific to foreign antigen-induced immune responses rather than to signaling required for B-cell development. ..
  21. Hernandez E, Leite M, Guerra M, Kruglov E, Bruna Romero O, Rodrigues M, et al. The spatial distribution of inositol 1,4,5-trisphosphate receptor isoforms shapes Ca2+ waves. J Biol Chem. 2007;282:10057-67 pubmed
    ..The subcellular distribution of InsP3R isoforms may critically determine the repertoire of spatial patterns of Ca(2+) signals. ..
  22. El Daher S, Patel Y, Siddiqua A, Hassock S, Edmunds S, Maddison B, et al. Distinct localization and function of (1,4,5)IP(3) receptor subtypes and the (1,3,4,5)IP(4) receptor GAP1(IP4BP) in highly purified human platelet membranes. Blood. 2000;95:3412-22 pubmed
  23. Vanderheyden V, Devogelaere B, Missiaen L, De Smedt H, Bultynck G, Parys J. Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release by reversible phosphorylation and dephosphorylation. Biochim Biophys Acta. 2009;1793:959-70 pubmed publisher
  24. Jurkovicova D, Kopacek J, Stefanik P, Kubovcakova L, Zahradnikova A, Pastorekova S, et al. Hypoxia modulates gene expression of IP3 receptors in rodent cerebellum. Pflugers Arch. 2007;454:415-25 pubmed
    ..are most probably involved, as antioxidant quercetin abolished hypoxia-induced increase in both types 1 and 2 IP3 receptor. Ryanodine receptors of types 1 and 2 and sarco(endo)plasmic reticulum Ca(2+)-ATPase were not affected by ..
  25. Cardenas C, Liberona J, Molgo J, Colasante C, Mignery G, Jaimovich E. Nuclear inositol 1,4,5-trisphosphate receptors regulate local Ca2+ transients and modulate cAMP response element binding protein phosphorylation. J Cell Sci. 2005;118:3131-40 pubmed
  26. Hirata K, Dufour J, Shibao K, Knickelbein R, O Neill A, Bode H, et al. Regulation of Ca(2+) signaling in rat bile duct epithelia by inositol 1,4,5-trisphosphate receptor isoforms. Hepatology. 2002;36:284-96 pubmed
    ..Because Ca(i)(2+) is in part responsible for regulating ductular secretion, these findings also may have implications for the molecular basis of cholestatic disorders. ..
  27. Fritz N, Mironneau J, Macrez N, Morel J. Acetylcholine-induced Ca2+ oscillations are modulated by a Ca2+ regulation of InsP3R2 in rat portal vein myocytes. Pflugers Arch. 2008;456:277-83 pubmed
    ..have demonstrated that acetylcholine (ACh) evokes Ca2+ oscillations in vascular myocytes expressing InsP3R1 and InsP3R2, whereas transient responses are activated in vascular myocytes expressing InsP3R1 alone...
  28. Li C, Wang X, Vais H, Thompson C, Foskett J, White C. Apoptosis regulation by Bcl-x(L) modulation of mammalian inositol 1,4,5-trisphosphate receptor channel isoform gating. Proc Natl Acad Sci U S A. 2007;104:12565-70 pubmed
    ..Rather, apoptosis protection is conferred by enhanced spontaneous [Ca(2+)](i) signaling by Bcl-x(L) interaction with all isoforms of the InsP(3)R. ..
  29. Endo Y, Harada K, Fujishiro N, Funahashi H, Shioda S, Prestwich G, et al. Organelles containing inositol trisphosphate receptor type 2 in adrenal medullary cells. J Physiol Sci. 2006;56:415-23 pubmed
    ..The results suggest that the InsP(3)R2 was present in the ER, but not in secretory granules in AM cells. ..
  30. Micutkova L, Kvetnansky R, Krizanova O. Repeated immobilization stress reduces the gene expression of the type 1 and 2 IP3 receptors in stellate ganglia. Neurochem Int. 2003;43:557-61 pubmed
    ..The IP(3) receptor protein is reduced as well. Physiological relevance of our observations remains to be elucidated. ..
  31. Magnino F, Schmidt K, Mery L, Dufour J. Rat inositol 1,4,5-trisphosphate receptor isoform 2 interacts with itself in its C-terminal portion and upstream of the first transmembrane domain. Eur J Biochem. 2001;268:5981-8 pubmed
    ..These results advance our understanding of the molecular mechanisms that underlie the oligomerization and interactions of the InsP(3)R subunits during the opening/closing of the Ca(2+) channel. ..