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Gene Review

ITPR1  -  inositol 1,4,5-trisphosphate receptor, type 1

Homo sapiens

Synonyms: ACV, CLA4, INSP3R1, IP3 receptor isoform 1, IP3R, ...
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Disease relevance of ITPR1


Psychiatry related information on ITPR1

  • To determine whether InsP3R1/NCS-1 interaction could be functionally relevant in bipolar disorders, conditions in which NCS-1 is highly expressed, we tested the effect of lithium, a salt widely used for treatment of bipolar disorders [6].
  • Several studies have shown severe deficits in both IP3 receptor levels and PKC levels and activity in Alzheimer's disease brain, although the relationship of these changes to disease pathology is poorly understood [7].

High impact information on ITPR1

  • The inositol 1,4,5 trisphosphate (IP3) receptor (IP3R) is a Ca2+ release channel that responds to the second messenger IP3 [8].
  • Through these regulatory mechanisms, IP3R modulates diverse cellular functions, which include, but are not limited to, contraction/excitation, secretion, gene expression, and cellular growth [8].
  • We review the unique properties of the IP3R that facilitate cell-type and stimulus-dependent control of function, with special emphasis on protein-binding partners [8].
  • Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta [9].
  • Calcium release from inositol 1,4,5-trisphosphate (IP3)-sensitive stores is negatively regulated by binding of calmodulin to the IP3 receptor (IP3R) and the NO/cGMP/cGMP kinase I (cGKI) signalling pathway [9].

Chemical compound and disease context of ITPR1


Biological context of ITPR1


Anatomical context of ITPR1

  • Thrombin also induced translocation of a complex consisting of Rho, IP3R, and TRPC1 to the plasma membrane [19].
  • These results indicate that RYR1 functions as a Ca2+ release channel during BCR-stimulated Ca2+ signaling and suggest that complex Ca2+ signals that control the cellular activities of B cells may be generated by cooperation of the IP3 receptor and RYR1 [20].
  • We tested the hypothesis that RhoA, a monomeric GTP-binding protein, induces association of inositol trisphosphate receptor (IP3R) with transient receptor potential channel (TRPC1), and thereby activates store depletion-induced Ca2+ entry in endothelial cells [19].
  • Rho-induced association of IP3R with TRPC1 was dependent on actin filament polymerization because latrunculin (which inhibits actin polymerization) prevented both the association and Ca2+ entry [19].
  • Our results indicate that the activation of SOC in keratinocytes depends, at least partly, on the interaction of TRPC with PLCgamma1 and IP3R [21].

Associations of ITPR1 with chemical compounds


Physical interactions of ITPR1

  • Conformational coupling with the inositol 1,4,5-trisphosphate (IP3) receptor has been suggested as a possible mechanism of activation of TRPC3 channels and a region in the C terminus of TRPC3 has been shown to interact with the IP3 receptor as well as calmodulin (calmodulin/IP3 receptor-binding (CIRB) region) [25].
  • Multiserine phosphorylation of IRBIT was essential for the binding, and 10 of the 12 key amino acids in IP3R for IP3 recognition participated in binding to IRBIT [26].
  • We now report that FKBP12 binds the IP3R at residues 1400-1401, a leucyl-prolyl dipeptide epitope that structurally resembles FK506 [27].

Enzymatic interactions of ITPR1

  • The IP3 receptor is stoichiometrically phosphorylated by protein kinase C (PKC) and Ca2+ calmodulin-dependent protein kinase II (CaM kinase II) as well as by PKA [28].

Co-localisations of ITPR1

  • Moreover, IP3-R was translocated to and colocalized with EB aggregates and chlamydial inclusions and had a distribution very similar to that of SERCA 2 [29].

Regulatory relationships of ITPR1

  • In the present study, we showed that IRBIT suppresses the activation of IP3R by competing with IP3 by [3H]IP3 binding assays, in vitro Ca2+ release assays, and Ca2+ imaging of intact cells [26].

Other interactions of ITPR1


Analytical, diagnostic and therapeutic context of ITPR1


  1. Possible involvement of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers. Sakakura, C., Hagiwara, A., Fukuda, K., Shimomura, K., Takagi, T., Kin, S., Nakase, Y., Fujiyama, J., Mikoshiba, K., Okazaki, Y., Yamagishi, H. Anticancer Res. (2003) [Pubmed]
  2. Calcium released from intracellular stores inhibits GABAA-mediated currents in ganglion cells of the turtle retina. Akopian, A., Gabriel, R., Witkovsky, P. J. Neurophysiol. (1998) [Pubmed]
  3. Calcium signaling molecules in human cerebellum at midgestation and in ataxia. Zecevic, N., Milosevic, A., Ehrlich, B.E. Early Hum. Dev. (1999) [Pubmed]
  4. Enhancement of hyperthermia-induced apoptosis by local anesthetics on human histiocytic lymphoma U937 cells. Arai, Y., Kondo, T., Tanabe, K., Zhao, Q.L., Li, F.J., Ogawa, R., Li, M., Kasuya, M. J. Biol. Chem. (2002) [Pubmed]
  5. Inositol trisphosphate receptor gene expression and hormonal regulation in osteoblast-like cell lines and primary osteoblastic cell cultures. Kirkwood, K.L., Dziak, R., Bradford, P.G. J. Bone Miner. Res. (1996) [Pubmed]
  6. Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium. Schlecker, C., Boehmerle, W., Jeromin, A., DeGray, B., Varshney, A., Sharma, Y., Szigeti-Buck, K., Ehrlich, B.E. J. Clin. Invest. (2006) [Pubmed]
  7. Loss of inositol 1,4,5-trisphosphate receptor sites and decreased PKC levels correlate with staging of Alzheimer's disease neurofibrillary pathology. Kurumatani, T., Fastbom, J., Bonkale, W.L., Bogdanovic, N., Winblad, B., Ohm, T.G., Cowburn, R.F. Brain Res. (1998) [Pubmed]
  8. Inositol 1,4,5-trisphosphate receptors as signal integrators. Patterson, R.L., Boehning, D., Snyder, S.H. Annu. Rev. Biochem. (2004) [Pubmed]
  9. Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Schlossmann, J., Ammendola, A., Ashman, K., Zong, X., Huber, A., Neubauer, G., Wang, G.X., Allescher, H.D., Korth, M., Wilm, M., Hofmann, F., Ruth, P. Nature (2000) [Pubmed]
  10. Calphostin C triggers calcium-dependent apoptosis in human acute lymphoblastic leukemia cells. Zhu, D.M., Narla, R.K., Fang, W.H., Chia, N.C., Uckun, F.M. Clin. Cancer Res. (1998) [Pubmed]
  11. Selective inhibition of inositol 1,4,5-triphosphate-induced Ca2+ release in the CA1 region of the hippocampus in the ischemic gerbil. Nagata, E., Tanaka, K., Suzuki, S., Dembo, T., Fukuuchi, Y., Futatsugi, A., Mikoshiba, K. Neuroscience (1999) [Pubmed]
  12. Changes in IP3R1 and SERCA2b mRNA levels in the gerbil brain after chronic ethanol administration and transient cerebral ischemia-reperfusion. Xia, J., Simonyi, A., Sun, G.Y. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  13. MK-801, a non-competitive NMDA receptor antagonist, prevents postischemic decrease of inositol 1,4,5-trisphosphate receptor mRNA expression in mongolian gerbil brain. Uhm, C.S., Suh, Y.S., Park, J.B., Sohn, M.B., Rhyu, I.J., Kim, H. Neurosci. Lett. (1998) [Pubmed]
  14. Role of inositol 1,4,5-trisphosphate receptors in alpha1-adrenergic receptor-induced cardiomyocyte hypertrophy. Luo, D.L., Gao, J., Lan, X.M., Wang, G., Wei, S., Xiao, R.P., Han, Q.D. Acta Pharmacol. Sin. (2006) [Pubmed]
  15. Cdc2/cyclin B1 interacts with and modulates inositol 1,4,5-trisphosphate receptor (type 1) functions. Malathi, K., Li, X., Krizanova, O., Ondrias, K., Sperber, K., Ablamunits, V., Jayaraman, T. J. Immunol. (2005) [Pubmed]
  16. Signal transduction and gene expression regulated by calcium release from internal stores in excitable cells. Carrasco, M.A., Jaimovich, E., Kemmerling, U., Hidalgo, C. Biol. Res. (2004) [Pubmed]
  17. Role of inositol 1,4,5-trisphosphate receptors in regulating apoptotic signaling and heart failure. Gutstein, D.E., Marks, A.R. Heart and vessels. (1997) [Pubmed]
  18. Regulation of the type 1 inositol 1,4,5-trisphosphate receptor by phosphorylation at tyrosine 353. Cui, J., Matkovich, S.J., deSouza, N., Li, S., Rosemblit, N., Marks, A.R. J. Biol. Chem. (2004) [Pubmed]
  19. RhoA interaction with inositol 1,4,5-trisphosphate receptor and transient receptor potential channel-1 regulates Ca2+ entry. Role in signaling increased endothelial permeability. Mehta, D., Ahmmed, G.U., Paria, B.C., Holinstat, M., Voyno-Yasenetskaya, T., Tiruppathi, C., Minshall, R.D., Malik, A.B. J. Biol. Chem. (2003) [Pubmed]
  20. Skeletal muscle type ryanodine receptor is involved in calcium signaling in human B lymphocytes. Sei, Y., Gallagher, K.L., Basile, A.S. J. Biol. Chem. (1999) [Pubmed]
  21. Phospholipase cgamma1 is required for activation of store-operated channels in human keratinocytes. Tu, C.L., Chang, W., Bikle, D.D. J. Invest. Dermatol. (2005) [Pubmed]
  22. Dysregulated ryanodine receptors mediate cellular toxicity: restoration of normal phenotype by FKBP12.6. George, C.H., Higgs, G.V., Mackrill, J.J., Lai, F.A. J. Biol. Chem. (2003) [Pubmed]
  23. Multiple effects of caffeine on Ca2+ release and influx in human B lymphocytes. Sei, Y., Gallagher, K.L., Daly, J.W. Cell Calcium (2001) [Pubmed]
  24. The human type 1 inositol 1,4,5-trisphosphate receptor from T lymphocytes. Structure, localization, and tyrosine phosphorylation. Harnick, D.J., Jayaraman, T., Ma, Y., Mulieri, P., Go, L.O., Marks, A.R. J. Biol. Chem. (1995) [Pubmed]
  25. A calmodulin/inositol 1,4,5-trisphosphate (IP3) receptor-binding region targets TRPC3 to the plasma membrane in a calmodulin/IP3 receptor-independent process. Wedel, B.J., Vazquez, G., McKay, R.R., St J Bird, G., Putney, J.W. J. Biol. Chem. (2003) [Pubmed]
  26. IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor. Ando, H., Mizutani, A., Kiefer, H., Tsuzurugi, D., Michikawa, T., Mikoshiba, K. Mol. Cell (2006) [Pubmed]
  27. FKBP12 binds the inositol 1,4,5-trisphosphate receptor at leucine-proline (1400-1401) and anchors calcineurin to this FK506-like domain. Cameron, A.M., Nucifora, F.C., Fung, E.T., Livingston, D.J., Aldape, R.A., Ross, C.A., Snyder, S.H. J. Biol. Chem. (1997) [Pubmed]
  28. Inositol trisphosphate receptor: phosphorylation by protein kinase C and calcium calmodulin-dependent protein kinases in reconstituted lipid vesicles. Ferris, C.D., Huganir, R.L., Bredt, D.S., Cameron, A.M., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  29. Localization of intracellular Ca2+ stores in HeLa cells during infection with Chlamydia trachomatis. Majeed, M., Krause, K.H., Clark, R.A., Kihlström, E., Stendahl, O. J. Cell. Sci. (1999) [Pubmed]
  30. Characterization and mapping of the 12 kDa FK506-binding protein (FKBP12)-binding site on different isoforms of the ryanodine receptor and of the inositol 1,4,5-trisphosphate receptor. Bultynck, G., De Smet, P., Rossi, D., Callewaert, G., Missiaen, L., Sorrentino, V., De Smedt, H., Parys, J.B. Biochem. J. (2001) [Pubmed]
  31. T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice: is IP3R type 1 essential for T-cell-receptor signalling? Hirota, J., Baba, M., Matsumoto, M., Furuichi, T., Takatsu, K., Mikoshiba, K. Biochem. J. (1998) [Pubmed]
  32. Binding of IRBIT to the IP3 receptor: determinants and functional effects. Devogelaere, B., Nadif Kasri, N., Derua, R., Waelkens, E., Callewaert, G., Missiaen, L., Parys, J.B., De Smedt, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  33. Overexpression of CALNUC (nucleobindin) increases agonist and thapsigargin releasable Ca2+ storage in the Golgi. Lin, P., Yao, Y., Hofmeister, R., Tsien, R.Y., Farquhar, M.G. J. Cell Biol. (1999) [Pubmed]
  34. Molecular cloning of a cDNA for the human inositol 1,4,5-trisphosphate receptor type 1, and the identification of a third alternatively spliced variant. Nucifora, F.C., Li, S.H., Danoff, S., Ullrich, A., Ross, C.A. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  35. Inositol 1,4,5-trisphosphate receptor (type 1) phosphorylation and modulation by Cdc2. Malathi, K., Kohyama, S., Ho, M., Soghoian, D., Li, X., Silane, M., Berenstein, A., Jayaraman, T. J. Cell. Biochem. (2003) [Pubmed]
  36. Differential regulation of two types of intracellular calcium release channels during end-stage heart failure. Go, L.O., Moschella, M.C., Watras, J., Handa, K.K., Fyfe, B.S., Marks, A.R. J. Clin. Invest. (1995) [Pubmed]
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