View source for Inositol trisphosphate receptor

{{also|Ryanodine-Inositol 1,4,5-triphosphate receptor calcium channels}}
{{infobox protein
| Name = [[ITPR1|inositol 1,4,5-trisphosphate receptor, type 1]]<ref name="pmid15664189">{{cite journal |vauthors=Bosanac I, Yamazaki H, Matsu-Ura T, Michikawa T, Mikoshiba K, Ikura M |title=Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor |journal=Mol. Cell |volume=17 |issue=2 |pages=193–203 |date=January 2005 |pmid=15664189 |doi=10.1016/j.molcel.2004.11.047 |url=}}</ref>
| caption = Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor
| image = 1XZZ.pdb.jpg
| width = 
| HGNCid = 6180
| Symbol = ITPR1
| AltSymbols = 
| EntrezGene = 3708
| OMIM = 147265
| RefSeq = NM_002222
| UniProt = Q14643
| PDB = 
| ECnumber = 
| Chromosome = 3
| Arm = p
| Band = 26.1
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[ITPR2|inositol 1,4,5-trisphosphate receptor, type 2]]
| caption = 
| image = 
| width = 
| HGNCid =Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor 6181
| Symbol = ITPR2
| AltSymbols = 
| EntrezGene = 3709
| OMIM = 600144
| RefSeq = NM_002223
| UniProt = Q14571
| PDB = 
| ECnumber = 
| Chromosome = 12
| Arm = p
| Band = 11.23
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[ITPR3|inositol 1,4,5-trisphosphate receptor, type 3]]
| caption = 
| image = 
| width = 
| HGNCid = 6182
| Symbol = ITPR3
| AltSymbols = 
| EntrezGene = 3710
| OMIM = 147267
| RefSeq = NM_002224
| UniProt = Q14573
| PDB = 
| ECnumber = 
| Chromosome = 6
| Arm = p
| Band = 21.31
| LocusSupplementaryData = 
}}

'''Inositol trisphosphate receptor''' ('''InsP3R''') is a membrane [[glycoprotein]] complex acting as a [[calcium channel|Ca<sup>2+</sup> channel]] activated by [[inositol trisphosphate]] (InsP3). 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.<ref name="pmid12442173">{{cite journal  |vauthors=Bosanac I, Alattia JR, Mal TK, etal |title=Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand |journal=Nature |volume=420 |issue=6916 |pages=696–700 |date=December 2002 |pmid=12442173 |doi=10.1038/nature01268 |url=}}</ref> Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca<sup>2+</sup> from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca<sup>2+</sup> signals characterized by complex patterns relative to both space and time, such as Ca<sup>2+</sup> waves and oscillations.<ref name="pmid9243320">{{cite journal |vauthors=Yoshida Y, Imai S |title=Structure and function of inositol 1,4,5-trisphosphate receptor |journal=Jpn. J. Pharmacol. |volume=74 |issue=2 |pages=125–37 |date=June 1997 |pmid=9243320 |doi= 10.1254/jjp.74.125|url=}}</ref> 

==Discovery==

The InsP3 receptor was first purified from rat cerebellum by neuroscientists Surachai Supattapone and Solomon Snyder at Johns Hopkins University School of Medicine.<ref name="pmid2826483">{{cite journal | vauthors = Supattapone S, Worley PF, Baraban JM, Snyder SH | title = Solubilization, purification, and characterization of an inositol trisphosphate receptor | journal = The Journal of Biological Chemistry | volume = 263 | issue = 3 | pages = 1530–4 | date = January 1988 | pmid = 2826483 | doi = | url = http://www.jbc.org/content/263/3/1530.full.pdf }}</ref>

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.<ref name="pmid2762133">{{cite journal| author=Furuichi T, Yoshikawa S, Mikoshiba K| title=Nucleotide sequence of cDNA encoding P400 protein in the mouse cerebellum. | journal=Nucleic Acids Res | year= 1989 | volume= 17 | issue= 13 | pages= 5385-6 | pmid=2762133 | doi= | pmc=318125 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2762133  }} </ref>  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]].<ref name="pmid2554142">{{cite journal| author=Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K| title=Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400. | journal=Nature | year= 1989 | volume= 342 | issue= 6245 | pages= 32-8 | pmid=2554142 | doi=10.1038/342032a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2554142  }} </ref>

==Distribution==
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]].

==Structure==
The asymmetric structure consists of an N-terminal [[beta trefoil fold|beta-trefoil domain]] and a C-terminal [[alpha helix|alpha helical]] domain with a folding pattern similar to an [[armadillo repeat]] fold. The split formed by the two terminals contains multiple arginine and lysine residues that coordinate the three phosphoryl groups of InsP3R.<ref name="pmid12442173"/> The InsP3R complex is formed of four 313 kDa subunits. In amphibians, fish and mammals, there are 3 [[paralogs]] and these can form homo- or hetero-oligomers. InsP3R-1 is the most widely expressed of these three and is found in all tissue types and all developmental stages of life. It is additionally the means for further InsP3 receptor diversity in that it has as many as four splice sites with as many as 9 different optional exons or exon variants. Combinations of these can be introduced into a given transcript in order to modulate its pharmacological activity.

==See also==
* [[Inositol]]
* [[Inositol phosphate]]
** [[Inositol monophosphate]]
** [[Inositol trisphosphate]]
** [[Inositol pentakisphosphate]]
** [[Inositol hexaphosphate]]
* [[MRVI1]] associated through complex formation.

== References ==
{{reflist}}

==External links==
* {{MeshName|Inositol+Trisphosphate+Receptor}}

{{Lipid_signaling}}
{{Ion channels|g1}}

{{DEFAULTSORT:Inositol Trisphosphate Receptor}}
[[Category:Signal transduction]]
[[Category:Transmembrane receptors]]
[[Category:Inositol]]