ITPR2 Research Reagents

Inositol 1,4,5-trisphosphate receptor type 2 is a protein in humans that is encoded by ITPR2 gene. Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. This release is regulated by cAMP both dependently and independently of PKA (By similarity).

The following ITPR2 reagents supplied by CUSABIO are manufactured under a strict quality control system. Multiple applications have been validated and solid technical support is offered.

ITPR2 Antibodies

ITPR2 Antibodies for Homo sapiens (Human)

ITPR2 Proteins

ITPR2 Proteins for Homo sapiens (Human)

ITPR2 Proteins for Bos taurus (Bovine)

ITPR2 Proteins for Rattus norvegicus (Rat)

ITPR2 Background

The ITPR2 encodes inositol 1,4,5-trisphosphate receptor type 2, one of intracellular calcium release channels mediates the calcium signaling [1]. All three IP3R isoforms are tetramers, with each subunit encompassing an N-terminus, six transmembrane domains, and a C-terminal tail [2][3]. The N-terminus contains an inositol 1,4,5-trisphosphate (IP3)-binding domain, a suppressor domain that inhibits IP3 binding, and a regulatory domain [4]. This regulatory domain contains binding sites for Ca2+ and ATP as well as consensus phosphorylation sites [2][5][6]. The transmembrane and C-terminal domains are essential for tetramerization of IP3Rs [7][8]. The full-length isoforms are 60–70% identical in primary sequence, with the N-terminal ligand-binding and C-terminal channel domains sharing the highest similarity [9]. IP3R2 exhibits the highest IP3 binding affinity, followed by IP3R1 and then IP3R3 [10][11]. The high sensitivity to IP3 makes IP3R2 a target for anti-apoptotic proteins (e.g. Bcl-2) in B-cell cancers. Akl H et al. demonstrated that cancer cells particularly expressing high levels of IP3R2 are addicted to IP3R/Bcl-2 complex formation and disruption of these complexes using a cell-permeable peptide results in pro-apoptotic Ca2+ signaling and cell death [12]. The binding of IP3R and IP3R2 redistributes Ca2+ from the ER to cytosol, leading to an increase in the cytosolic Ca2+ concentration [13]. Elevated Ca2+ levels further activates Ca2+-dependent proteins, inducing a cascade of intracellular responses, including cell division, cell proliferation, apoptosis, fertilization, development, behavior, memory, and learning [14]. The study of Jeremy Petravicz et al. provides the first functional evidence that IP3R2 is the only IP3R isoform expressed by astrocytes, IP3R2 is not required for neuronal Gq-linked GPCR-mediated Ca2+ elevations and removal of astrocyte Ca2+ increases has no effect on basal neuronal excitatory activity [15]. IP3R2 is not only implicated in apoptosis but also in the induction of senescence, another tumour-suppressive mechanism.

[1] Yamamoto-Hino M, Sugiyama T, et al. Cloning and characterization of human type 2 and type 3 inositol 1,4,5-trisphosphate receptors [J].
[2] Michikawa T., Hamanaka H., et al. Transmembrane topology and sites of N-glycosylation of inositol 1,4,5-trisphosphate receptor [J]. J. Biol. Chem. 1994, 269, 9184-9189.
[3] Yoshikawa F., Morita M., et al. Mutational analysis of the ligand binding site of the inositol 1,4,5-trisphosphate receptor [J]. J. Biol. Chem. 1996, 271, 18277-18284.
[4] Yoshikawa F., Iwasaki H., et al. Cooperative formation of the ligand-binding site of the inositol 1,4, 5-trisphosphate receptor by two separable domains [J]. J. Biol. Chem. 1999, 274, 328-334.
[5] Patel S., Joseph S. K., et al. Molecular properties of inositol 1,4,5-trisphosphate receptors [J]. Cell Calcium 1999, 25, 247-264.
[6] Foskett J. K., White C., et al. Inositol trisphosphate receptor Ca2+ release channels [J]. Physiol. Rev. 2007, 87, 593-658.
[7] Mignery G. A. and Sudhof, T. C. The ligand binding site and transduction mechanism in the inositol-1,4,5-triphosphate receptor [J]. EMBO J. 1990, 9, 3893-3898.
[8] Sayers L. G., Miyawaki A., et al. Intracellular targeting and homotetramer formation of a truncated inositol 1,4,5-trisphosphate receptor-green fluorescent protein chimera in Xenopus laevis oocytes: evidence for the involvement of the transmembrane spanning domain in endoplasmic reticulum targeting and homotetramer complex formation [J]. Biochem. J. 1997, 323 (Pt 1), 273-280. Recept. Channels. 1994, 2 (1): 9-22.
[9] Patel S, Joseph SK, et al. Molecular properties of inositol 1,4,5-trisphosphate receptors [J]. Cell Calcium. 1999 Mar;25(3):247-64.
[10] Iwai M., Michikawa T., et al. Molecular Basis of the Isoform-specific Ligand-binding Affinity of Inositol 1,4,5-Trisphosphate Receptors [J]. J. Biol. Chem. 2007, 282, 12755-12764.
[11] Iwai M., Tateishi Y., Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant [J]. J. Biol. Chem. 2005, 280, 10305-10317.
[12] Akl H, Monaco G, et al. IP3R2 levels dictate the apoptotic sensitivity of diffuse large B-cell lymphoma cells to an IP3R-derived peptide targeting the BH4 domain of Bcl-2 [J]. Cell Death Dis. 2013 May 16;4:e632.
[13] Berridge M.J. Inositol trisphosphate and calcium signalling [J]. Nature. 1993; 361: 315-325.
[14] Furuichi T. and Mikoshiba K. Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain [J]. J. Neurochem. 1995; 64: 953-960.
[15] Jeremy Petravicz, Todd A. Fiacco, et al. Loss of IP3Receptor-Dependent Ca2+ Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity [J]. The Journal of Neuroscience, 2008, 28(19):4967-4973.

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