ITPR3 Membrane Protein Introduction

Introduction of ITPR3

Inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) is a protein which in humans is encoded by the ITPR3 gene. ITPR3 is both a receptor for inositol triphosphate and a calcium channel. ITPR3 is mapped to chromosome 20p12 and participates in the phosphatidylinositol signaling pathway. ITPR3 contains an N terminal cytoplasmic ligand binding domain, a channel forming hydrophobic domain made of six membrane-spanning segments, and a linking modulatory domain. ITPR3 is mainly expressed in the plasma membrane and presents in the paranodal regions of the nodes of Ranvier.

Basic Information of ITPR3
Protein Name	Inositol 1,4,5-trisphosphate receptor type 3
Gene Name	ITPR3
Aliases	IP3 receptor isoform 3 (IP3R 3, InsP3R3), Type 3 inositol 1,4,5-trisphosphate receptor (Type 3 InsP3 receptor)
Organism	Homo sapiens (Human)
UniProt ID	Q14573
Transmembrane Times	6
Length (aa)	2671
Sequence	MSEMSSFLHIGDIVSLYAEGSVNGFISTLGLVDDRCVVEPAAGDLDNPPKKFRDCLFKVCPMNRYSAQKQYWKAKQTKQDKEKIADVVLLQKLQHAAQMEQKQNDTENKKVHGDVVKYGSVIQLLHMKSNKYLTVNKRLPALLEKNAMRVTLDATGNEGSWLFIQPFWKLRSNGDNVVVGDKVILNPVNAGQPLHASNYELSDNAGCKEVNSVNCNTSWKINLFMQFRDHLEEVLKGGDVVRLFHAEQEKFLTCDEYKGKLQVFLRTTLRQSATSATSSNALWEVEVVHHDPCRGGAGHWNGLYRFKHLATGNYLAAEENPSYKGDASDPKAAGMGAQGRTGRRNAGEKIKYCLVAVPHGNDIASLFELDPTTLQKTDSFVPRNSYVRLRHLCTNTWIQSTNVPIDIEEERPIRLMLGTCPTKEDKEAFAIVSVPVSEIRDLDFANDASSMLASAVEKLNEGFISQNDRRFVIQLLEDLVFFVSDVPNNGQNVLDIMVTKPNRERQKLMREQNILKQVFGILKAPFREKGGEGPLVRLEELSDQKNAPYQHMFRLCYRVLRHSQEDYRKNQEHIAKQFGMMQSQIGYDILAEDTITALLHNNRKLLEKHITKTEVETFVSLVRKNREPRFLDYLSDLCVSNHIAIPVTQELICKCVLDPKNSDILIRTELRPVKEMAQSHEYLSIEYSEEEVWLTWTDKNNEHHEKSVRQLAQEARAGNAHDENVLSYYRYQLKLFARMCLDRQYLAIDEISQQLGVDLIFLCMADEMLPFDLRASFCHLMLHVHVDRDPQELVTPVKFARLWTEIPTAITIKDYDSNLNASRDDKKNKFANTMEFVEDYLNNVVSEAVPFANEEKNKLTFEVVSLAHNLIYFGFYSFSELLRLTRTLLGIIDCVQGPPAMLQAYEDPGGKNVRRSIQGVGHMMSTMVLSRKQSVFSAPSLSAGASAAEPLDRSKFEENEDIVVMETKLKILEILQFILNVRLDYRISYLLSVFKKEFVEVFPMQDSGADGTAPAFDSTTANMNLDRIGEQAEAMFGVGKTSSMLEVDDEGGRMFLRVLIHLTMHDYAPLVSGALQLLFKHFSQRQEAMHTFKQVQLLISAQDVENYKVIKSELDRLRTMVEKSELWVDKKGSGKGEEVEAGAAKDKKERPTDEEGFLHPPGEKSSENYQIVKGILERLNKMCGVGEQMRKKQQRLLKNMDAHKVMLDLLQIPYDKGDAKMMEILRYTHQFLQKFCAGNPGNQALLHKHLHLFLTPGLLEAETMQHIFLNNYQLCSEISEPVLQHFVHLLATHGRHVQYLDFLHTVIKAEGKYVKKCQDMIMTELTNAGDDVVVFYNDKASLAHLLDMMKAARDGVEDHSPLMYHISLVDLLAACAEGKNVYTEIKCTSLLPLEDVVSVVTHEDCITEVKMAYVNFVNHCYVDTEVEMKEIYTSNHIWTLFENFTLDMARVCSKREKRVADPTLEKYVLSVVLDTINAFFSSPFSENSTSLQTHQTIVVQLLQSTTRLLECPWLQQQHKGSVEACIRTLAMVAKGRAILLPMDLDAHISSMLSSGASCAAAAQRNASSYKATTRAFPRVTPTANQWDYKNIIEKLQDIITALEERLKPLVQAELSVLVDVLHWPELLFLEGSEAYQRCESGGFLSKLIQHTKDLMESEEKLCIKVLRTLQQMLLKKTKYGDRGNQLRKMLLQNYLQNRKSTSRGDLPDPIGTGLDPDWSAIAATQCRLDKEGATKLVCDLITSTKNEKIFQESIGLAIHLLDGGNTEIQKSFHNLMMSDKKSERFFKVLHDRMKRAQQETKSTVAVNMNDLGSQPHEDREPVDPTTKGRVASFSIPGSSSRYSLGPSLRRGHEVSERVQSSEMGTSVLIMQPILRFLQLLCENHNRDLQNFLRCQNNKTNYNLVCETLQFLDIMCGSTTGGLGLLGLYINEDNVGLVIQTLETLTEYCQGPCHENQTCIVTHESNGIDIITALILNDISPLCKYRMDLVLQLKDNASKLLLALMESRHDSENAERILISLRPQELVDVIKKAYLQEEERENSEVSPREVGHNIYILALQLSRHNKQLQHLLKPVKRIQEEEAEGISSMLSLNNKQLSQMLKSSAPAQEEEEDPLAYYENHTSQIEIVRQDRSMEQIVFPVPGICQFLTEETKHRLFTTTEQDEQGSKVSDFFDQSSFLHNEMEWQRKLRSMPLIYWFSRRMTLWGSISFNLAVFINIIIAFFYPYMEGASTGVLDSPLISLLFWILICFSIAALFTKRYSIRPLIVALILRSIYYLGIGPTLNILGALNLTNKIVFVVSFVGNRGTFIRGYKAMVMDMEFLYHVGYILTSVLGLFAHELFYSILLFDLIYREETLFNVIKSVTRNGRSILLTALLALILVYLFSIVGFLFLKDDFILEVDRLPNNHSTASPLGMPHGAAAFVDTCSGDKMDCVSGLSVPEVLEEDRELDSTERACDTLLMCIVTVMNHGLRNGGGVGDILRKPSKDESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTFADLRSEKQKKEEILKTTCFICGLERDKFDNKTVSFEEHIKLEHNMWNYLYFIVLVRVKNKTDYTGPESYVAQMIKNKNLDWFPRMRAMSLVSNEGEGEQNEIRILQDKLNSTMKLVSHLTAQLNELKEQMTEQRKRRQRLGFVDVQNCISR

Function of ITPR3 Membrane Protein

ITPR3 is involved in Ca²⁺ mobilization from the ER in the intestinal epithelium and platelets movements. The amplitude, frequency, and subcellular localization of Ca²⁺ signals play an important role in determining cellular responses. ITPR3 requires the second messenger inositol 1,4,5-trisphosphate (IP3) for activation but it is also regulated physiologically via cross-talk with other signaling pathways. Acting as a messenger for inositol triphosphate, ITPR3 mediates the pathway signaling of calcium, this is why isoform ITPR3 loses feedback of inhibition with cytosol calcium. ITPR3 channels play an important role in the taste feeling pathway of sweet, bitter and umami tastes the gustatory system. ITPR3 is reported to play a crucial role in the regulation of apoptosis signaling in T lymphocytes, and in the development of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Graves disease.

Fig. ITPR2 functions in Wnt/Ca²⁺ signaling. (Zhang, 2014)

Application of ITPR3 Membrane Protein in Literature

Huang Y.C., et al. Single nucleotide polymorphism rs2229634 in the ITPR3 gene is associated with the risk of developing coronary artery aneurysm in children with Kawasaki disease. Int J Immunogenet. 2010, 37(6): 439-43. PubMed ID: 20618519

This article suggests that the rs2229634 SNP in the ITPR3 gene is closely related to the risk of CAA formation in Taiwanese KD patients.
Oishi T., et al. A functional SNP in the NKX2.5-binding site of ITPR3 promoter is associated with susceptibility to systemic lupus erythematosus in Japanese population. J Hum Genet. 2008, 53(2): 151-62. PubMed ID: 18219441

This article demonstrates that relationship between ITPR3 and NKX2.5 plays a crucial role in the pathogenesis of SLE genetically and functionally.
Qu H.Q., et al. The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II. Genes Immun. 2008, 9(3): 264-6. PubMed ID: 18340361

In this article, they strongly suggest the association of ITPR3 single nucleotide polymorphisms (SNPs) rs2296336 with T1D but in a direction opposite to that reported.
Tordoff M.G. and Ellis H.T. Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol triphosphate receptor 3 gene. Physiol Genomics. 2013, 45(18): 834-55. PubMed ID: 23859941

This article shows that a spontaneous mutation of Itpr3 in a progenitor of the BTBR strain produces a heretofore unrecognized dysfunction of GPCR-mediated taste transduction.
Ellis H.T., et al. Itpr3 Is responsible for the mouse tufted (tf) locus. J Hered. 2013, 104(2): 295-7. PubMed ID: 23100490

In this article, the authors use a combination of positional cloning methods and complementation mapping to identify Itpr3, the inositol triphosphate receptor type 3, as the gene responsible for the tf locus.

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Reference

Zhang Y, et al. (2014). KIAA1199 and its biological role in human cancer and cancer cells (review). Oncol Rep. 31(4): 1503-8.

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