ID ITPR3_HUMAN Reviewed; 2671 AA. AC Q14573; Q14649; Q5TAQ2; DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 14-OCT-2008, sequence version 2. DT 08-NOV-2023, entry version 215. DE RecName: Full=Inositol 1,4,5-trisphosphate receptor type 3; DE AltName: Full=IP3 receptor isoform 3; DE Short=IP3R 3; DE Short=InsP3R3; DE AltName: Full=Type 3 inositol 1,4,5-trisphosphate receptor; DE Short=Type 3 InsP3 receptor; GN Name=ITPR3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-2436. RX PubMed=8081734; RA Yamamoto-Hino M., Sugiyama T., Hikiti K., Mattei M.-G., Hasegawa K., RA Sekine S., Sakurada K., Miyawaki A., Furuichi T., Hasegawa M., RA Mikoshiba K.; RT "Cloning and characterization of human type 2 and type 3 inositol 1,4,5- RT trisphosphate receptors."; RL Recept. Channels 2:9-22(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8288584; DOI=10.1016/s0021-9258(17)42246-0; RA Maranto A.R.; RT "Primary structure, ligand binding, and localization of the human type 3 RT inositol 1,4,5-trisphosphate receptor expressed in intestinal epithelium."; RL J. Biol. Chem. 269:1222-1230(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP INTERACTION WITH CABP1. RX PubMed=12032348; DOI=10.1073/pnas.102006299; RA Yang J., McBride S., Mak D.-O.D., Vardi N., Palczewski K., Haeseleer F., RA Foskett J.K.; RT "Identification of a family of calcium sensors as protein ligands of RT inositol trisphosphate receptor Ca(2+) release channels."; RL Proc. Natl. Acad. Sci. U.S.A. 99:7711-7716(2002). RN [6] RP INTERACTION WITH TRPV4. RX PubMed=18826956; DOI=10.1074/jbc.c800184200; RA Garcia-Elias A., Lorenzo I.M., Vicente R., Valverde M.A.; RT "IP3 receptor binds to and sensitizes TRPV4 channel to osmotic stimuli via RT a calmodulin-binding site."; RL J. Biol. Chem. 283:31284-31288(2008). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-916; SER-934 AND SER-1832, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP INTERACTION WITH TMBIM4/LFG4. RX PubMed=19553469; DOI=10.1091/mbc.e09-05-0385; RA de Mattia F., Gubser C., van Dommelen M.M., Visch H.J., Distelmaier F., RA Postigo A., Luyten T., Parys J.B., de Smedt H., Smith G.L., Willems P.H., RA van Kuppeveld F.J.; RT "Human Golgi antiapoptotic protein modulates intracellular calcium RT fluxes."; RL Mol. Biol. Cell 20:3638-3645(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1813, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-916 AND SER-2670, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-916; SER-934; SER-1832; RP SER-1834; SER-2609 AND SER-2670, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP INTERACTION WITH CEMIP. RX PubMed=23936024; DOI=10.1371/journal.pone.0069473; RA Tiwari A., Schneider M., Fiorino A., Haider R., Okoniewski M.J., RA Roschitzki B., Uzozie A., Menigatti M., Jiricny J., Marra G.; RT "Early insights into the function of KIAA1199, a markedly overexpressed RT protein in human colorectal tumors."; RL PLoS ONE 8:E69473-E69473(2013). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1832, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP INTERACTION WITH TMEM203. RX PubMed=25996873; DOI=10.1371/journal.pone.0127480; RA Shambharkar P.B., Bittinger M., Latario B., Xiong Z., Bandyopadhyay S., RA Davis V., Lin V., Yang Y., Valdez R., Labow M.A.; RT "TMEM203 is a novel regulator of intracellular calcium homeostasis and is RT required for spermatogenesis."; RL PLoS ONE 10:E0127480-E0127480(2015). RN [16] RP INTERACTION WITH BCL2L10. RX PubMed=27995898; DOI=10.7554/elife.19896; RA Bonneau B., Ando H., Kawaai K., Hirose M., Takahashi-Iwanaga H., RA Mikoshiba K.; RT "IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, RT and by promoting ER-mitochondria contact."; RL Elife 5:e19896-e19896(2016). RN [17] RP VARIANT CMT1J MET-1424, AND INVOLVEMENT IN CMT1J. RX PubMed=24627108; DOI=10.1007/s00415-014-7289-8; RA Schabhuettl M., Wieland T., Senderek J., Baets J., Timmerman V., RA De Jonghe P., Reilly M.M., Stieglbauer K., Laich E., Windhager R., Erwa W., RA Trajanoski S., Strom T.M., Auer-Grumbach M.; RT "Whole-exome sequencing in patients with inherited neuropathies: outcome RT and challenges."; RL J. Neurol. 261:970-982(2014). RN [18] RP VARIANTS CMT1J MET-615 AND CYS-2524, CHARACTERIZATION OF VARIANT CMT1J RP MET-615, INVOLVEMENT IN CMT1J, AND FUNCTION. RX PubMed=32949214; DOI=10.1002/acn3.51190; RA Roenkkoe J., Molchanova S., Revah-Politi A., Pereira E.M., Auranen M., RA Toppila J., Kvist J., Ludwig A., Neumann J., Bultynck G., Humblet-Baron S., RA Liston A., Paetau A., Rivera C., Harms M.B., Tyynismaa H., Ylikallio E.; RT "Dominant mutations in ITPR3 cause Charcot-Marie-Tooth disease."; RL Ann. Clin. Transl. Neurol. 7:1962-1972(2020). CC -!- FUNCTION: Receptor for inositol 1,4,5-trisphosphate, a second messenger CC that mediates the release of intracellular calcium (By similarity). CC Involved in cellular calcium ion homeostasis (PubMed:32949214). CC {ECO:0000250|UniProtKB:P70227, ECO:0000269|PubMed:32949214}. CC -!- SUBUNIT: Homotetramer. Interacts with TRPC1, TRPC3 and TRPC4. Interacts CC with TRPV4 (PubMed:18826956). Interacts with SIGMAR1 (By similarity). CC Interacts with PML and AKT1 (By similarity). Interacts with IRAG2 (via CC coiled-coil domain) (By similarity). Interacts with CABP1 CC (PubMed:12032348). Interacts with TMBIM4/LFG4 (PubMed:19553469). CC Interacts with CEMIP (PubMed:23936024). Interacts with TESPA1 (By CC similarity). Interacts with TMEM203 (PubMed:25996873). Interacts with CC BOK; regulates ITPR3 expression (By similarity). Interacts with BCL2L10 CC (PubMed:27995898). {ECO:0000250|UniProtKB:P70227, CC ECO:0000250|UniProtKB:Q63269, ECO:0000269|PubMed:12032348, CC ECO:0000269|PubMed:18826956, ECO:0000269|PubMed:19553469, CC ECO:0000269|PubMed:23936024, ECO:0000269|PubMed:25996873, CC ECO:0000269|PubMed:27995898}. CC -!- INTERACTION: CC Q14573; Q92560: BAP1; NbExp=12; IntAct=EBI-351055, EBI-1791447; CC Q14573; Q13507: TRPC3; NbExp=5; IntAct=EBI-351055, EBI-520807; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass CC membrane protein. CC -!- TISSUE SPECIFICITY: Expressed in intestinal crypt and villus epithelial CC cells. CC -!- DOMAIN: The receptor contains a calcium channel in its C-terminal CC extremity. Its large N-terminal cytoplasmic region has the ligand- CC binding site in the N-terminus and modulatory sites in the middle CC portion immediately upstream of the channel region. CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylated by AKT1 on CC serine and/or threonine residues (By similarity). {ECO:0000250}. CC -!- DISEASE: Charcot-Marie-Tooth disease, demyelinating, 1J (CMT1J) CC [MIM:620111]: An autosomal dominant demyelinating form of Charcot- CC Marie-Tooth disease, a disorder of the peripheral nervous system, CC characterized by progressive weakness and atrophy, initially of the CC peroneal muscles and later of the distal muscles of the arms. Charcot- CC Marie-Tooth disease is classified in two main groups on the basis of CC electrophysiologic properties and histopathology: primary peripheral CC demyelinating neuropathies (designated CMT1 when they are dominantly CC inherited) and primary peripheral axonal neuropathies (CMT2). CC Demyelinating neuropathies are characterized by severely reduced nerve CC conduction velocities (less than 38 m/sec), segmental demyelination and CC remyelination with onion bulb formations on nerve biopsy, slowly CC progressive distal muscle atrophy and weakness, absent deep tendon CC reflexes, and hollow feet. {ECO:0000269|PubMed:24627108, CC ECO:0000269|PubMed:32949214}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the InsP3 receptor family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D26351; BAA05385.1; -; mRNA. DR EMBL; U01062; AAC50064.1; -; mRNA. DR EMBL; AL139044; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX03744.1; -; Genomic_DNA. DR CCDS; CCDS4783.1; -. DR PIR; A49873; A49873. DR RefSeq; NP_002215.2; NM_002224.3. DR PDB; 6DQJ; EM; 3.49 A; A/B/C/D=1-2671. DR PDB; 6DQN; EM; 3.33 A; A/B/C/D=1-2671. DR PDB; 6DQS; EM; 4.12 A; A/B/C/D=1-2671. DR PDB; 6DQV; EM; 3.82 A; A/B/C/D=1-2671. DR PDB; 6DQZ; EM; 6.01 A; A/B/C/D=1-2671. DR PDB; 6DR0; EM; 4.47 A; A/B/C/D=1-2671. DR PDB; 6DR2; EM; 4.33 A; A/B/C/D=1-2671. DR PDB; 6DRA; EM; 3.96 A; A/B/C/D=1-2671. DR PDB; 6DRC; EM; 3.92 A; A/B/C/D=1-2671. DR PDB; 6UQK; EM; 3.77 A; A/B/C/D=4-2611. DR PDB; 7T3P; EM; 3.20 A; A/B/C/D=1-2611. DR PDB; 7T3Q; EM; 3.30 A; A/B/C/D=1-2611. DR PDB; 7T3R; EM; 3.40 A; A/B/C/D=1-2611. DR PDB; 7T3T; EM; 3.80 A; A/B/C/D=1-2611. DR PDB; 7T3U; EM; 3.70 A; A/B/C/D=1-2611. DR PDBsum; 6DQJ; -. DR PDBsum; 6DQN; -. DR PDBsum; 6DQS; -. DR PDBsum; 6DQV; -. DR PDBsum; 6DQZ; -. DR PDBsum; 6DR0; -. DR PDBsum; 6DR2; -. DR PDBsum; 6DRA; -. DR PDBsum; 6DRC; -. DR PDBsum; 6UQK; -. DR PDBsum; 7T3P; -. DR PDBsum; 7T3Q; -. DR PDBsum; 7T3R; -. DR PDBsum; 7T3T; -. DR PDBsum; 7T3U; -. DR AlphaFoldDB; Q14573; -. DR SMR; Q14573; -. DR BioGRID; 109915; 227. DR CORUM; Q14573; -. DR IntAct; Q14573; 57. DR MINT; Q14573; -. DR STRING; 9606.ENSP00000363435; -. DR BindingDB; Q14573; -. DR ChEMBL; CHEMBL3904; -. DR DrugBank; DB00201; Caffeine. DR GlyGen; Q14573; 4 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q14573; -. DR PhosphoSitePlus; Q14573; -. DR SwissPalm; Q14573; -. DR BioMuta; ITPR3; -. DR DMDM; 209572633; -. DR EPD; Q14573; -. DR jPOST; Q14573; -. DR MassIVE; Q14573; -. DR MaxQB; Q14573; -. DR PaxDb; 9606-ENSP00000363435; -. DR PeptideAtlas; Q14573; -. DR ProteomicsDB; 60051; -. DR Pumba; Q14573; -. DR Antibodypedia; 1294; 164 antibodies from 27 providers. DR DNASU; 3710; -. DR Ensembl; ENST00000374316.9; ENSP00000363435.4; ENSG00000096433.11. DR Ensembl; ENST00000605930.3; ENSP00000475177.1; ENSG00000096433.11. DR GeneID; 3710; -. DR KEGG; hsa:3710; -. DR MANE-Select; ENST00000605930.3; ENSP00000475177.1; NM_002224.4; NP_002215.2. DR UCSC; uc063nyh.1; human. DR AGR; HGNC:6182; -. DR CTD; 3710; -. DR DisGeNET; 3710; -. DR GeneCards; ITPR3; -. DR HGNC; HGNC:6182; ITPR3. DR HPA; ENSG00000096433; Low tissue specificity. DR MalaCards; ITPR3; -. DR MIM; 147267; gene. DR MIM; 620111; phenotype. DR neXtProt; NX_Q14573; -. DR OpenTargets; ENSG00000096433; -. DR PharmGKB; PA29980; -. DR VEuPathDB; HostDB:ENSG00000096433; -. DR eggNOG; KOG3533; Eukaryota. DR GeneTree; ENSGT00940000157078; -. DR HOGENOM; CLU_000206_1_0_1; -. DR InParanoid; Q14573; -. DR OMA; WLMWTDK; -. DR OrthoDB; 5480299at2759; -. DR PhylomeDB; Q14573; -. DR TreeFam; TF312815; -. DR PathwayCommons; Q14573; -. DR Reactome; R-HSA-112043; PLC beta mediated events. DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis. DR Reactome; R-HSA-139853; Elevation of cytosolic Ca2+ levels. DR Reactome; R-HSA-1489509; DAG and IP3 signaling. DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion. DR Reactome; R-HSA-4086398; Ca2+ pathway. DR Reactome; R-HSA-422356; Regulation of insulin secretion. DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-HSA-5578775; Ion homeostasis. DR Reactome; R-HSA-5607763; CLEC7A (Dectin-1) induces NFAT activation. DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis. DR Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste. DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR SignaLink; Q14573; -. DR BioGRID-ORCS; 3710; 8 hits in 1163 CRISPR screens. DR ChiTaRS; ITPR3; human. DR GeneWiki; ITPR3; -. DR GenomeRNAi; 3710; -. DR Pharos; Q14573; Tchem. DR PRO; PR:Q14573; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q14573; Protein. DR Bgee; ENSG00000096433; Expressed in cartilage tissue and 183 other tissues. DR Genevisible; Q14573; HS. DR GO; GO:0045177; C:apical part of cell; ISS:BHF-UCL. DR GO; GO:0005903; C:brush border; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL. DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0043209; C:myelin sheath; ISS:BHF-UCL. DR GO; GO:0043025; C:neuronal cell body; ISS:BHF-UCL. DR GO; GO:0005640; C:nuclear outer membrane; ISS:BHF-UCL. DR GO; GO:0005730; C:nucleolus; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0031095; C:platelet dense tubular network membrane; TAS:Reactome. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0016529; C:sarcoplasmic reticulum; IBA:GO_Central. DR GO; GO:0030667; C:secretory granule membrane; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB. DR GO; GO:0043533; F:inositol 1,3,4,5 tetrakisphosphate binding; ISS:BHF-UCL. DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IDA:BHF-UCL. DR GO; GO:0005220; F:inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; IDA:BHF-UCL. DR GO; GO:0000822; F:inositol hexakisphosphate binding; ISS:BHF-UCL. DR GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central. DR GO; GO:0055074; P:calcium ion homeostasis; IMP:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:BHF-UCL. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IBA:GO_Central. DR GO; GO:0051592; P:response to calcium ion; IDA:BHF-UCL. DR GO; GO:0050913; P:sensory perception of bitter taste; IEA:Ensembl. DR GO; GO:0050916; P:sensory perception of sweet taste; IEA:Ensembl. DR GO; GO:0050909; P:sensory perception of taste; TAS:Reactome. DR GO; GO:0050917; P:sensory perception of umami taste; IEA:Ensembl. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 2.80.10.50; -; 2. DR Gene3D; 1.25.10.30; IP3 receptor type 1 binding core, RIH domain; 1. DR InterPro; IPR014821; Ins145_P3_rcpt. DR InterPro; IPR000493; InsP3_rcpt. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR036300; MIR_dom_sf. DR InterPro; IPR016093; MIR_motif. DR InterPro; IPR013662; RIH_assoc-dom. DR InterPro; IPR000699; RIH_dom. DR InterPro; IPR015925; Ryanodine_IP3_receptor. DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf. DR PANTHER; PTHR45816:SF1; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR TYPE 3; 1. DR PANTHER; PTHR45816; MIR DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF08709; Ins145_P3_rec; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF02815; MIR; 1. DR Pfam; PF08454; RIH_assoc; 1. DR Pfam; PF01365; RYDR_ITPR; 2. DR PRINTS; PR00779; INSP3RECEPTR. DR SMART; SM00472; MIR; 4. DR SUPFAM; SSF100909; IP3 receptor type 1 binding core, domain 2; 2. DR SUPFAM; SSF82109; MIR domain; 2. DR PROSITE; PS50919; MIR; 5. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Calcium channel; Calcium transport; KW Charcot-Marie-Tooth disease; Disease variant; Endoplasmic reticulum; KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane; KW Neurodegeneration; Neuropathy; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..2671 FT /note="Inositol 1,4,5-trisphosphate receptor type 3" FT /id="PRO_0000153928" FT TOPO_DOM 1..2202 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2203..2223 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2224..2235 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 2236..2256 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2257..2264 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2265..2285 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2286..2325 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 2326..2346 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2347..2368 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2369..2389 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2390..2496 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 2497..2517 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2518..2671 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 113..173 FT /note="MIR 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 174..224 FT /note="MIR 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 232..288 FT /note="MIR 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 295..372 FT /note="MIR 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 378..434 FT /note="MIR 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT REGION 322..342 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1132..1163 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1809..1848 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1132..1161 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1831..1845 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 266..270 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000250" FT BINDING 507..510 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000250" FT BINDING 567..569 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000250" FT MOD_RES 916 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 934 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1813 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1832 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 1834 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2609 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2670 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT VARIANT 374 FT /note="L -> W (in dbSNP:rs2229646)" FT /id="VAR_049604" FT VARIANT 615 FT /note="V -> M (in CMT1J; decreased inositol trisphosphate- FT mediated calcium release and altered calcium homeostasis in FT patient fibroblasts)" FT /evidence="ECO:0000269|PubMed:32949214" FT /id="VAR_087822" FT VARIANT 667 FT /note="R -> Q (in dbSNP:rs11963294)" FT /id="VAR_046978" FT VARIANT 742 FT /note="D -> E (in dbSNP:rs2229633)" FT /id="VAR_046979" FT VARIANT 1029 FT /note="G -> V (in dbSNP:rs2296333)" FT /id="VAR_046980" FT VARIANT 1424 FT /note="T -> M (in CMT1J; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:24627108" FT /id="VAR_087823" FT VARIANT 1552 FT /note="L -> V (in dbSNP:rs9461899)" FT /id="VAR_046981" FT VARIANT 1850 FT /note="R -> Q (in dbSNP:rs12528378)" FT /id="VAR_046982" FT VARIANT 2398 FT /note="E -> Q (in dbSNP:rs2229641)" FT /id="VAR_046983" FT VARIANT 2436 FT /note="L -> V (in dbSNP:rs2229642)" FT /evidence="ECO:0000269|PubMed:8081734" FT /id="VAR_046984" FT VARIANT 2524 FT /note="R -> C (in CMT1J)" FT /evidence="ECO:0000269|PubMed:32949214" FT /id="VAR_087824" FT CONFLICT 524 FT /note="A -> V (in Ref. 2; AAC50064)" FT /evidence="ECO:0000305" FT CONFLICT 562 FT /note="H -> Y (in Ref. 2; AAC50064)" FT /evidence="ECO:0000305" FT CONFLICT 989 FT /note="Y -> H (in Ref. 1; BAA05385)" FT /evidence="ECO:0000305" FT CONFLICT 1143 FT /note="A -> T (in Ref. 2; AAC50064)" FT /evidence="ECO:0000305" FT CONFLICT 1391 FT /note="L -> V (in Ref. 2; AAC50064)" FT /evidence="ECO:0000305" FT CONFLICT 1496..1497 FT /note="TI -> PV (in Ref. 2; AAC50064)" FT /evidence="ECO:0000305" FT CONFLICT 1674 FT /note="L -> V (in Ref. 2; AAC50064)" FT /evidence="ECO:0000305" FT CONFLICT 2187..2188 FT /note="KL -> NV (in Ref. 1; BAA05385 and 2; AAC50064)" FT /evidence="ECO:0000305" SQ SEQUENCE 2671 AA; 304106 MW; 04D1957A53320EEE CRC64; MSEMSSFLHI GDIVSLYAEG SVNGFISTLG LVDDRCVVEP AAGDLDNPPK KFRDCLFKVC PMNRYSAQKQ YWKAKQTKQD KEKIADVVLL QKLQHAAQME QKQNDTENKK VHGDVVKYGS VIQLLHMKSN KYLTVNKRLP ALLEKNAMRV TLDATGNEGS WLFIQPFWKL RSNGDNVVVG DKVILNPVNA GQPLHASNYE LSDNAGCKEV NSVNCNTSWK INLFMQFRDH LEEVLKGGDV VRLFHAEQEK FLTCDEYKGK LQVFLRTTLR QSATSATSSN ALWEVEVVHH DPCRGGAGHW NGLYRFKHLA TGNYLAAEEN PSYKGDASDP KAAGMGAQGR TGRRNAGEKI KYCLVAVPHG NDIASLFELD PTTLQKTDSF VPRNSYVRLR HLCTNTWIQS TNVPIDIEEE RPIRLMLGTC PTKEDKEAFA IVSVPVSEIR DLDFANDASS MLASAVEKLN EGFISQNDRR FVIQLLEDLV FFVSDVPNNG QNVLDIMVTK PNRERQKLMR EQNILKQVFG ILKAPFREKG GEGPLVRLEE LSDQKNAPYQ HMFRLCYRVL RHSQEDYRKN QEHIAKQFGM MQSQIGYDIL AEDTITALLH NNRKLLEKHI TKTEVETFVS LVRKNREPRF LDYLSDLCVS NHIAIPVTQE LICKCVLDPK NSDILIRTEL RPVKEMAQSH EYLSIEYSEE EVWLTWTDKN NEHHEKSVRQ LAQEARAGNA HDENVLSYYR YQLKLFARMC LDRQYLAIDE ISQQLGVDLI FLCMADEMLP FDLRASFCHL MLHVHVDRDP QELVTPVKFA RLWTEIPTAI TIKDYDSNLN ASRDDKKNKF ANTMEFVEDY LNNVVSEAVP FANEEKNKLT FEVVSLAHNL IYFGFYSFSE LLRLTRTLLG IIDCVQGPPA MLQAYEDPGG KNVRRSIQGV GHMMSTMVLS RKQSVFSAPS LSAGASAAEP LDRSKFEENE DIVVMETKLK ILEILQFILN VRLDYRISYL LSVFKKEFVE VFPMQDSGAD GTAPAFDSTT ANMNLDRIGE QAEAMFGVGK TSSMLEVDDE GGRMFLRVLI HLTMHDYAPL VSGALQLLFK HFSQRQEAMH TFKQVQLLIS AQDVENYKVI KSELDRLRTM VEKSELWVDK KGSGKGEEVE AGAAKDKKER PTDEEGFLHP PGEKSSENYQ IVKGILERLN KMCGVGEQMR KKQQRLLKNM DAHKVMLDLL QIPYDKGDAK MMEILRYTHQ FLQKFCAGNP GNQALLHKHL HLFLTPGLLE AETMQHIFLN NYQLCSEISE PVLQHFVHLL ATHGRHVQYL DFLHTVIKAE GKYVKKCQDM IMTELTNAGD DVVVFYNDKA SLAHLLDMMK AARDGVEDHS PLMYHISLVD LLAACAEGKN VYTEIKCTSL LPLEDVVSVV THEDCITEVK MAYVNFVNHC YVDTEVEMKE IYTSNHIWTL FENFTLDMAR VCSKREKRVA DPTLEKYVLS VVLDTINAFF SSPFSENSTS LQTHQTIVVQ LLQSTTRLLE CPWLQQQHKG SVEACIRTLA MVAKGRAILL PMDLDAHISS MLSSGASCAA AAQRNASSYK ATTRAFPRVT PTANQWDYKN IIEKLQDIIT ALEERLKPLV QAELSVLVDV LHWPELLFLE GSEAYQRCES GGFLSKLIQH TKDLMESEEK LCIKVLRTLQ QMLLKKTKYG DRGNQLRKML LQNYLQNRKS TSRGDLPDPI GTGLDPDWSA IAATQCRLDK EGATKLVCDL ITSTKNEKIF QESIGLAIHL LDGGNTEIQK SFHNLMMSDK KSERFFKVLH DRMKRAQQET KSTVAVNMND LGSQPHEDRE PVDPTTKGRV ASFSIPGSSS RYSLGPSLRR GHEVSERVQS SEMGTSVLIM QPILRFLQLL CENHNRDLQN FLRCQNNKTN YNLVCETLQF LDIMCGSTTG GLGLLGLYIN EDNVGLVIQT LETLTEYCQG PCHENQTCIV THESNGIDII TALILNDISP LCKYRMDLVL QLKDNASKLL LALMESRHDS ENAERILISL RPQELVDVIK KAYLQEEERE NSEVSPREVG HNIYILALQL SRHNKQLQHL LKPVKRIQEE EAEGISSMLS LNNKQLSQML KSSAPAQEEE EDPLAYYENH TSQIEIVRQD RSMEQIVFPV PGICQFLTEE TKHRLFTTTE QDEQGSKVSD FFDQSSFLHN EMEWQRKLRS MPLIYWFSRR MTLWGSISFN LAVFINIIIA FFYPYMEGAS TGVLDSPLIS LLFWILICFS IAALFTKRYS IRPLIVALIL RSIYYLGIGP TLNILGALNL TNKIVFVVSF VGNRGTFIRG YKAMVMDMEF LYHVGYILTS VLGLFAHELF YSILLFDLIY REETLFNVIK SVTRNGRSIL LTALLALILV YLFSIVGFLF LKDDFILEVD RLPNNHSTAS PLGMPHGAAA FVDTCSGDKM DCVSGLSVPE VLEEDRELDS TERACDTLLM CIVTVMNHGL RNGGGVGDIL RKPSKDESLF PARVVYDLLF FFIVIIIVLN LIFGVIIDTF ADLRSEKQKK EEILKTTCFI CGLERDKFDN KTVSFEEHIK LEHNMWNYLY FIVLVRVKNK TDYTGPESYV AQMIKNKNLD WFPRMRAMSL VSNEGEGEQN EIRILQDKLN STMKLVSHLT AQLNELKEQM TEQRKRRQRL GFVDVQNCIS R //