Inositol 1,4,5-triphosphate receptor associated 1 (IRAG1)

Inositol 1,4,5-triphosphate receptor associated 1 (IRAG1) is a ~125 kDa type II membrane protein located on the endoplasmic reticulum. It interacts directly with the inositol 1,4,5-triphosphate receptor (IP3R-I) and cyclic GMP-dependent kinase Iβ (PKGIβ), forming a macrocomplex that regulates IP3-induced Ca(2+) release from intracellular stores. Upon phosphorylation by PKGIβ, IRAG1 inhibits IP3R-I-mediated Ca(2+) release in a cGMP-dependent fashion, thereby facilitating nitric oxide-dependent smooth muscle relaxation and inhibiting platelet activation. IRAG1 is implicated in several physiological processes such as gastrointestinal motility, vascular relaxation, and platelet function. Genetic alterations and deficiencies in IRAG1 have been linked to conditions including achalasia, Moyamoya disease, hypertension, and may play a role in certain cancers as a tumor suppressor

Other names

IRAGMRVI1Jaw1-related protein MRVI1JAW1LMurine retrovirus integration site 1 homologIP3R-associated cGMP kinase substrateInositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrateInositol 1,4,5-triphosphate-associated cGMP kinase substrate

Nitric oxide (NO) stimulates guanylate cyclase, raising cGMP levels. cGMP activates PKGIβ, which then phosphorylates IRAG1. This inhibits IP3-induced Ca(2+) release from the endoplasmic reticulum, leading to smooth muscle relaxation and inhibition of platelet aggregation