ITPR2 Membrane Protein Introduction

Introduction of ITPR2

Inositol 1,4,5-trisphosphate receptor, type 2, also known as ITPR2, is a protein which in humans is encoded by the ITPR2 gene. ITPR2 contains six membrane-spanning segments, an N terminal cytoplasmic ligand binding domain, a central transducing/modulatory domain, a C-terminal channel domain, and five MIR domains. ITPR2 is mainly located on the endoplasmic reticulum (ER) and concentrated in the vicinity of the node, and the outer Schwann cell cytoplasm.

Function of ITPR2 Membrane Protein

ITPR2 functions as a receptor for inositol 1,4,5-trisphosphate and a calcium channel. It also acts as a second messenger that mediates the release of intracellular calcium. This release is directed by cAMP dependently/independently of PKA. ITPR2 also controls other biological processes, including cellular response to ethanol, platelet activation, regulation of cardiac conduction and insulin secretion. It also regulates releasing of sequestered calcium ion into the cytosol and responds to hypoxia, as well as signal transduction. The apical concentration of ITPR2 is essential for the formation of Ca(2+) waves in hepatocytes. It has been documented that the pericanalicular calcium signaling mediated by ITPR2 plays an important role in maintaining bile salt secretion through posttranslational regulation of ABCB11, suggesting that loss or redistribution of ITPR2 may contribute to the pathophysiology of intrahepatic cholestasis.

Fig.1 Pathway by which ITPR2 might contribute to cell death. (van Es, 2007)

Application of ITPR2 Membrane Protein in Literature

1. van Es M.A., et al. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol. 2007, 6(10): 869-77. PubMed ID: 17827064
   
   

   The authors show that genetic variation in ITPR2 is a susceptibility factor for ALS. ITPR2 is a strong candidate susceptibility gene for ALS because it is involved in glutamate-mediated neurotransmission. It is one of the main regulators of intracellular calcium concentrations and has an important role in apoptosis.

2. Wiel C., et al. Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence. Nat Commun. 2014, 5: 3792. PubMed ID: 24797322
   
   

   This article shows that ITPR2 triggers calcium release from the ER, followed by mitochondrial calcium accumulation through MCU channels. Mitochondrial calcium accumulation results in a subsequent decrease in mitochondrial membrane potential, reactive oxygen species accumulation, and senescence.

3. Zhang F., et al. Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. Arthritis Rheumatol. 2015, 67(1): 176-81. PubMed ID: 25303641
   
   

   In this article, they strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study shows us something new about the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.

4. Zhang N., et al. Germline genetic variations in PDZD2 and ITPR2 genes are associated with clear cell renal cell carcinoma in Chinese population. Oncotarget. 2017, 8(15): 24196-24201. PubMed ID: 26918600
   
   

   This article demonstrates genetic variations in PDZD2 and ITPR2 are ccRCC-risk associated in Chinese population.

5. Fernández-Santiago R., et al. No evidence of association of FLJ10986 and ITPR2 with ALS in a large German cohort. Neurobiol Aging. 2011, 32(3): 551.e1-4. PubMed ID: 19464757
   
   

   The article is not in favor of the association of several SNPs with SALS, while it suggests a possible population-specific effect for FLJ10986 and ITPR2 that do not modulate the risk for SALS in the German population.

ITPR2 Preparation Options

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Reference

1. van Es M A, et al. (2007). ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol. 6(10): 869-77.

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