Inositol 1,3,4,5-tetrakisphosphate receptor (InsP4R)

The Inositol 1,3,4,5-tetrakisphosphate (InsP4) receptor, primarily identified as the protein GAP1IP4BP (also known as RASA3), is a critical component of the intracellular signaling network that responds to phosphoinositide second messengers (UniProt: Q14644). It specifically binds InsP4, which is generated from InsP3 by the enzyme IP3 3-kinase, and functions as a GTPase-activating protein (GAP) to regulate the activity of Ras-family proteins (PubMed: 7651514). The receptor is thought to play a significant role in calcium homeostasis, potentially modulating store-operated calcium entry or the movement of calcium between intracellular compartments (PubMed: 1651279). In physiological contexts, it is essential for maintaining platelets in a quiescent state; its loss or inhibition leads to premature platelet activation and clearance, contributing to thrombocytopenia (PubMed: 25361228). Furthermore, its role in the Ras-MAPK pathway makes it a subject of interest in oncology, as its dysregulation can contribute to aberrant cell proliferation and survival. Despite its biological importance, there are currently no approved therapeutic agents that specifically target the InsP4 receptor, though it remains a target of interest for treating thrombotic and malignant conditions.

Other names

InsP4-sensitive calcium regulatory proteinGAP1IP4BPRASA3Ras GTPase-activating protein 3IP4RInositol 1,3,4,5-tetrakisphosphate-binding protein

The receptor acts as a GTPase-activating protein (GAP) for Ras and Rap GTPases and modulates intracellular calcium levels by binding the second messenger inositol 1,3,4,5-tetrakisphosphate (InsP4).