Inositol Trisphosphate Receptor

InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca²⁺ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca²⁺ signals characterized by complex patterns relative to both space and time, such as Ca²⁺ waves and oscillations.

inositol 1,4,5-trisphosphate receptor, type 1
Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor
Identifiers
Symbol	ITPR1
NCBI gene	3708
HGNC	6180
OMIM	147265
RefSeq	NM_002222
UniProt	Q14643
Other data
Locus	Chr. 3 p26.1
Search for Structures Swiss-model Domains InterPro

inositol 1,4,5-trisphosphate receptor, type 3
Single-particle cryo-EM structure of the IP3-bound resting state.
Identifiers
Symbol	ITPR3
NCBI gene	3710
HGNC	6182
OMIM	147267
RefSeq	NM_002224
UniProt	Q14573
Other data
Locus	Chr. 6 p21.31
Search for Structures Swiss-model Domains InterPro

The InsP3 receptor was first purified from rat cerebellum by neuroscientists Surachai Supattapone and Solomon Snyder at Johns Hopkins University School of Medicine.

The cDNA of the InsP3 receptor was first cloned in the laboratory of Katsuhiko Mikoshiba. The initial sequencing was reported as an unknown protein enriched in the cerebellum called P400. The large size of this open reading frame indicated a molecular weight similar to the protein purified biochemically, and soon thereafter it was confirmed that the protein p400 was in fact the inositol trisphosphate receptor.

The receptor has a broad tissue distribution but is especially abundant in the cerebellum. Most of the InsP3Rs are found integrated into the endoplasmic reticulum.

Several X-ray crystallographic and electron cryomicroscopic (cryo-EM) structures of IP₃Rs from mouse, rat, and human have defined the overall architecture of the channel. The 1.2 MDa C4-symmetric assembly consists of an ER-embedded transmembrane domain (TMD) in a domain-swapped 6 transmembrane (6TM) cation channel fold that is capped by a large cytosolic domain (CD). In this manner, IP₃Rs share significant homology with the much larger and distantly-related RyRs. The CD contains all known ligand binding sites, including the IP₃ binding site, two Ca²⁺ binding sites, an adenine nucleotide binding site, and a C₂H₂ Zn²⁺ finger fold. A comprehensive Ca²⁺-dependent conformational landscape has recently been defined by cryo-EM.

• Inositol
• Inositol phosphate
  • Inositol monophosphate
  • Inositol trisphosphate
  • Inositol pentakisphosphate
  • Inositol hexaphosphate
• MRVI1 associated through complex formation.