Inositol 1,4,5-trisphosphate receptor-interacting protein family (IPR026250)

Short name: ITPRIP_fam

Overlapping homologous superfamilies


Family relationships


The inositol 1,4,5-trisphosphate receptor (IP(3)R) is a large, endoplasmic reticulum (ER)-resident protein that is a key regulator of intracellular Ca(2+) signalling [PMID: 16990268]. Inositol 1,4,5-trisphosphate is formed in response to the activation of G protein-coupled receptors or tyrosine kinase receptors located in the plasma membrane, which elicit IP(3)R-mediated Ca(2+) release from ER stores [PMID: 16990268].

The IP(3)R contains an N-terminal IP(3) recognition site and a C-terminal Ca(2+)-channel domain; between them is a large interaction domain for regulatory proteins, including calmodulin, chromgranins, glyceraldehyde-3- phosphate dehydrogenase, RACK1 and caldendrin [PMID: 16990268]. These proteins regulate IP(3)R in diverse ways, but only two regulators have been shown to influence Ca(2+) sensitivity [PMID: 16990268].

A protein termed DANGER has been identified as a novel IP(3)R-interacting protein [PMID: 16990268]. DANGER is membrane-associated and predicted to contain a partial MAB-21 domain. It is expressed in a wide variety of neuronal cell lineages, where it localises with IP(3)R to membranes in the cell periphery. DANGER interacts with IP(3)R in vitro and co-immuno- precipitates with IP(3)R from cellular preparations; it robustly enhances Ca(2+)-mediated inhibition of IP(3)R Ca(2+) release without affecting IP(3) binding in microsomal assays, and inhibits gating in single-channel recordings of IP(3)R. The protein appears to allosterically modulate the sensitivity of IP(3)R to Ca(2+) inhibition, which probably alters IP(3)R-mediated Ca(2+) dynamics in cells where DANGER and IP(3)R are co-expressed [PMID: 16990268].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.