ID ITPR1_HUMAN Reviewed; 2758 AA. AC Q14643; E7EPX7; E9PDE9; Q14660; Q99897; DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 26-JUN-2013, sequence version 3. DT 27-MAR-2024, entry version 241. DE RecName: Full=Inositol 1,4,5-trisphosphate receptor type 1; DE AltName: Full=IP3 receptor isoform 1; DE Short=IP3R 1; DE Short=InsP3R1; DE AltName: Full=Type 1 inositol 1,4,5-trisphosphate receptor; DE Short=Type 1 InsP3 receptor; GN Name=ITPR1; Synonyms=INSP3R1; 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] (ISOFORM 4). RC TISSUE=Myeloid, and Uterus; RX PubMed=7945203; DOI=10.1042/bj3020781; RA Yamada N., Makino Y., Clark R.A., Pearson D.W., Mattei M.-G., Guenet J.-L., RA Ohama E., Fujino I., Miyawaki A., Furuichi T., Mikoshiba K.; RT "Human inositol 1,4,5-trisphosphate type-1 receptor, InsP3R1: structure, RT function, regulation of expression and chromosomal localization."; RL Biochem. J. 302:781-790(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND PHOSPHORYLATION. RC TISSUE=T-cell; RX PubMed=7852357; DOI=10.1074/jbc.270.6.2833; RA Harnick D.J., Jayaraman T., Ma Y., Mulieri P., Go L.O., Marks A.R.; RT "The human type 1 inositol 1,4,5-trisphosphate receptor from T lymphocytes. RT Structure, localization, and tyrosine phosphorylation."; RL J. Biol. Chem. 270:2833-2840(1995). RN [3] RP SEQUENCE REVISION TO 431; 1012-1017; 1460; 1823; 2324; 2330; 2334; 2337; RP 2346; 2358; 2361; 2372; 2396; 2418; 2426; 2434 AND 2741. RA Marks A.; RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND ALTERNATIVE RP SPLICING. RC TISSUE=Brain; RX PubMed=7500840; DOI=10.1016/0169-328x(95)00089-b; RA Nucifora F.C. Jr., Li S.-H., Danoff S., Ullrich A., Ross C.A.; RT "Molecular cloning of a cDNA for the human inositol 1,4,5-trisphosphate RT receptor type 1, and the identification of a third alternatively spliced RT variant."; RL Brain Res. Mol. Brain Res. 32:291-296(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1548-1723 (ISOFORMS 3 AND 4). RX PubMed=8648241; DOI=10.1080/095530096145544; RA Yan J., Khanna K.K., Lavin M.F.; RT "Induction of inositol 1,4,5 trisphosphate receptor genes by ionizing RT radiation."; RL Int. J. Radiat. Biol. 69:539-546(1996). RN [7] 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 [8] RP INTERACTION WITH CABP1. RX PubMed=14685260; DOI=10.1038/sj.emboj.7600037; RA Kasri N.N., Holmes A.M., Bultynck G., Parys J.B., Bootman M.D., RA Rietdorf K., Missiaen L., McDonald F., De Smedt H., Conway S.J., RA Holmes A.B., Berridge M.J., Roderick H.L.; RT "Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins."; RL EMBO J. 23:312-321(2004). RN [9] RP INTERACTION WITH ERP44. RX PubMed=15652484; DOI=10.1016/j.cell.2004.11.048; RA Higo T., Hattori M., Nakamura T., Natsume T., Michikawa T., Mikoshiba K.; RT "Subtype-specific and ER lumenal environment-dependent regulation of RT inositol 1,4,5-trisphosphate receptor type 1 by ERp44."; RL Cell 120:85-98(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [11] RP INTERACTION WITH AHCYL1, AND MUTAGENESIS OF ARG-241; LYS-249; ARG-265; RP THR-267; ARG-269; ARG-504; ARG-506; LYS-508; ARG-511; TYR-567; ARG-568 AND RP LYS-569. RX PubMed=16793548; DOI=10.1016/j.molcel.2006.05.017; RA Ando H., Mizutani A., Kiefer H., Tsuzurugi D., Michikawa T., Mikoshiba K.; RT "IRBIT suppresses IP3 receptor activity by competing with IP3 for the RT common binding site on the IP3 receptor."; RL Mol. Cell 22:795-806(2006). RN [12] RP INTERACTION WITH IRAG1. RX PubMed=16990611; DOI=10.1182/blood-2005-10-026294; RA Antl M., von Bruehl M.-L., Eiglsperger C., Werner M., Konrad I., Kocher T., RA Wilm M., Hofmann F., Massberg S., Schlossmann J.; RT "IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and RT thrombus formation."; RL Blood 109:552-559(2007). RN [13] RP INVOLVEMENT IN SCA15. RX PubMed=17590087; DOI=10.1371/journal.pgen.0030108; RA van de Leemput J., Chandran J., Knight M.A., Holtzclaw L.A., Scholz S., RA Cookson M.R., Houlden H., Gwinn-Hardy K., Fung H.-C., Lin X., Hernandez D., RA Simon-Sanchez J., Wood N.W., Giunti P., Rafferty I., Hardy J., Storey E., RA Gardner R.J.M., Forrest S.M., Fisher E.M.C., Russell J.T., Cai H., RA Singleton A.B.; RT "Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 RT in humans."; RL PLoS Genet. 3:1076-1082(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598 AND SER-1764, AND RP 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 [15] RP INTERACTION WITH AHCYL1 AND AHCYL2. RX PubMed=19220705; DOI=10.1111/j.1471-4159.2009.05979.x; RA Ando H., Mizutani A., Mikoshiba K.; RT "An IRBIT homologue lacks binding activity to inositol 1,4,5-trisphosphate RT receptor due to the unique N-terminal appendage."; RL J. Neurochem. 109:539-550(2009). RN [16] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-2512. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598, AND IDENTIFICATION BY RP 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 [18] RP INTERACTION WITH TESPA1. RX PubMed=23650607; DOI=10.1016/j.fob.2012.08.005; RA Matsuzaki H., Fujimoto T., Ota T., Ogawa M., Tsunoda T., Doi K., RA Hamabashiri M., Tanaka M., Shirasawa S.; RT "Tespa1 is a novel inositol 1,4,5-trisphosphate receptor binding protein in RT T and B lymphocytes."; RL FEBS Open Bio 2:255-259(2012). RN [19] RP INTERACTION WITH BOK. RX PubMed=23884412; DOI=10.1074/jbc.m113.496570; RA Schulman J.J., Wright F.A., Kaufmann T., Wojcikiewicz R.J.; RT "The Bcl-2 protein family member Bok binds to the coupling domain of RT inositol 1,4,5-trisphosphate receptors and protects them from proteolytic RT cleavage."; RL J. Biol. Chem. 288:25340-25349(2013). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598 AND SER-1764, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598, 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 [22] RP INTERACTION WITH AHCYL1 AND 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 [23] RP VARIANT SCA15 LEU-1083. RX PubMed=18579805; DOI=10.1212/01.wnl.0000311277.71046.a0; RA Hara K., Shiga A., Nozaki H., Mitsui J., Takahashi Y., Ishiguro H., RA Yomono H., Kurisaki H., Goto J., Ikeuchi T., Tsuji S., Nishizawa M., RA Onodera O.; RT "Total deletion and a missense mutation of ITPR1 in Japanese SCA15 RT families."; RL Neurology 71:547-551(2008). RN [24] RP VARIANTS SCA29 ASP-602 AND MET-1562. RX PubMed=22986007; DOI=10.1186/1750-1172-7-67; RA Huang L., Chardon J.W., Carter M.T., Friend K.L., Dudding T.E., RA Schwartzentruber J., Zou R., Schofield P.W., Douglas S., Bulman D.E., RA Boycott K.M.; RT "Missense mutations in ITPR1 cause autosomal dominant congenital RT nonprogressive spinocerebellar ataxia."; RL Orphanet J. Rare Dis. 7:67-67(2012). RN [25] RP VARIANT SCA29 MET-1562. RX PubMed=26770814; DOI=10.1186/s40673-016-0040-8; RA Shadrina M.I., Shulskaya M.V., Klyushnikov S.A., Nikopensius T., Nelis M., RA Kivistik P.A., Komar A.A., Limborska S.A., Illarioshkin S.N., RA Slominsky P.A.; RT "ITPR1 gene p.Val1553Met mutation in Russian family with mild RT Spinocerebellar ataxia."; RL Cerebellum Ataxias 3:2-2(2016). RN [26] RP INVOLVEMENT IN GLSP, VARIANTS GLSP LEU-2601 AND LYS-2611 DEL, RP CHARACTERIZATION OF VARIANT GLSP LYS-2611 DEL, AND FUNCTION. RX PubMed=27108797; DOI=10.1016/j.ajhg.2016.03.004; RA Gerber S., Alzayady K.J., Burglen L., Bremond-Gignac D., Marchesin V., RA Roche O., Rio M., Funalot B., Calmon R., Durr A., Gil-da-Silva-Lopes V.L., RA Ribeiro Bittar M.F., Orssaud C., Heron B., Ayoub E., Berquin P., RA Bahi-Buisson N., Bole C., Masson C., Munnich A., Simons M., Delous M., RA Dollfus H., Boddaert N., Lyonnet S., Kaplan J., Calvas P., Yule D.I., RA Rozet J.M., Fares Taie L.; RT "Recessive and dominant de novo ITPR1 mutations cause Gillespie syndrome."; RL Am. J. Hum. Genet. 98:971-980(2016). RN [27] RP INVOLVEMENT IN GLSP, VARIANTS GLSP GLN-2109; ARG-2554 AND LYS-2611 DEL, AND RP SUBCELLULAR LOCATION. RX PubMed=27108798; DOI=10.1016/j.ajhg.2016.03.018; RG DDD Study; RA McEntagart M., Williamson K.A., Rainger J.K., Wheeler A., Seawright A., RA De Baere E., Verdin H., Bergendahl L.T., Quigley A., Rainger J., Dixit A., RA Sarkar A., Lopez Laso E., Sanchez-Carpintero R., Barrio J., Bitoun P., RA Prescott T., Riise R., McKee S., Cook J., McKie L., Ceulemans B., Meire F., RA Temple I.K., Prieur F., Williams J., Clouston P., Nemeth A.H., Banka S., RA Bengani H., Handley M., Freyer E., Ross A., van Heyningen V., Marsh J.A., RA Elmslie F., FitzPatrick D.R.; RT "A restricted repertoire of de novo mutations in ITPR1 cause Gillespie RT syndrome with evidence for dominant-negative effect."; RL Am. J. Hum. Genet. 98:981-992(2016). RN [28] RP MUTAGENESIS OF PRO-1059. RX PubMed=30197081; DOI=10.1016/j.cell.2018.08.019; RA Meyer K., Kirchner M., Uyar B., Cheng J.Y., Russo G., RA Hernandez-Miranda L.R., Szymborska A., Zauber H., Rudolph I.M., RA Willnow T.E., Akalin A., Haucke V., Gerhardt H., Birchmeier C., Kuehn R., RA Krauss M., Diecke S., Pascual J.M., Selbach M.; RT "Mutations in disordered regions can cause disease by creating dileucine RT motifs."; RL Cell 175:239-253(2018). CC -!- FUNCTION: Intracellular channel that mediates calcium release from the CC endoplasmic reticulum following stimulation by inositol 1,4,5- CC trisphosphate (PubMed:27108797). Involved in the regulation of CC epithelial secretion of electrolytes and fluid through the interaction CC with AHCYL1 (By similarity). Plays a role in ER stress-induced CC apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis CC by the activation of CaM kinase II, eventually leading to the CC activation of downstream apoptosis pathways (By similarity). CC {ECO:0000250|UniProtKB:P11881, ECO:0000269|PubMed:27108797}. CC -!- SUBUNIT: Homotetramer (By similarity). Interacts with TRPC4 (By CC similarity). The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with CC RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, CC redox state- and calcium-dependent manner which results in the CC inhibition the calcium channel activity. The strength of this CC interaction inversely correlates with calcium concentration. Part of CC cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CC CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with CC IRAG1 (PubMed:16990611). Interacts with CABP1 (via N-terminus) CC (PubMed:12032348, PubMed:14685260). Interacts with TESPA1. Interacts CC (when not phosphorylated) with AHCYL1 (when phosphorylated); the CC interaction suppresses inositol 1,4,5-trisphosphate binding to ITPR1 CC and is increased in the presence of BCL2L10 (PubMed:16793548, CC PubMed:27995898). Interacts with AHCYL2 (with lower affinity than with CC AHCYL1) (PubMed:19220705). Interacts with BCL2L10; the interaction is CC increased in the presence of AHCLY1 (PubMed:27995898). Interacts with CC BOK (via BH4 domain); protects ITPR1 from proteolysis by CASP3 during CC apoptosis (PubMed:23884412). {ECO:0000250|UniProtKB:P29994, CC ECO:0000250|UniProtKB:Q9TU34, ECO:0000269|PubMed:12032348, CC ECO:0000269|PubMed:14685260, ECO:0000269|PubMed:15652484, CC ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:16990611, CC ECO:0000269|PubMed:19220705, ECO:0000269|PubMed:23650607, CC ECO:0000269|PubMed:23884412, ECO:0000269|PubMed:27995898}. CC -!- INTERACTION: CC Q14643; O43865: AHCYL1; NbExp=3; IntAct=EBI-465548, EBI-2371423; CC Q14643; Q9HD36: BCL2L10; NbExp=7; IntAct=EBI-465548, EBI-2126349; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000305|PubMed:27108798}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane CC {ECO:0000250|UniProtKB:Q9TU34}; Multi-pass membrane protein CC {ECO:0000255}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:27108798}. Note=Endoplasmic reticulum and secretory CC granules (By similarity). {ECO:0000250|UniProtKB:Q9TU34}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Comment=There is a combination of three alternatively spliced domains CC at site SI, SIII and site SII (A and C). Experimental confirmation CC may be lacking for some isoforms.; CC Name=1; Synonyms=SISIIISIIAC; CC IsoId=Q14643-1; Sequence=Displayed; CC Name=2; Synonyms=SI-SIIISIIAC; CC IsoId=Q14643-2; Sequence=VSP_002687; CC Name=3; Synonyms=SISIII-SII; CC IsoId=Q14643-3; Sequence=VSP_002688, VSP_002689, VSP_002690; CC Name=4; Synonyms=SI-SIII-SII; CC IsoId=Q14643-4; Sequence=VSP_002687, VSP_002688, VSP_002689, CC VSP_002690; CC Name=5; Synonyms=SI-SIII-SIIAC; CC IsoId=Q14643-5; Sequence=VSP_002687, VSP_002688; CC Name=6; Synonyms=SISIIISIIA; CC IsoId=Q14643-6; Sequence=VSP_002690; CC Name=7; Synonyms=SI-SIII-SIIA; CC IsoId=Q14643-7; Sequence=VSP_002687, VSP_002690; CC Name=8; Synonyms=SI-SIII-SIIA; CC IsoId=Q14643-8; Sequence=VSP_002687, VSP_002688, VSP_002690; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:7500840}. 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. {ECO:0000269|PubMed:7852357}. CC -!- PTM: Ubiquitination at multiple lysines targets ITPR1 for proteasomal CC degradation. Approximately 40% of the ITPR1-associated ubiquitin is CC monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'- CC linked (By similarity). {ECO:0000250|UniProtKB:P29994}. CC -!- PTM: Phosphorylated by cAMP kinase (PKA). Phosphorylation prevents the CC ligand-induced opening of the calcium channels. Phosphorylation by PKA CC increases the interaction with inositol 1,4,5-trisphosphate and CC decreases the interaction with AHCYL1. {ECO:0000250|UniProtKB:P11881}. CC -!- PTM: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of CC ITPR1 stability and function. {ECO:0000250|UniProtKB:P11881}. CC -!- DISEASE: Spinocerebellar ataxia 15 (SCA15) [MIM:606658]: CC Spinocerebellar ataxia is a clinically and genetically heterogeneous CC group of cerebellar disorders. Patients show progressive incoordination CC of gait and often poor coordination of hands, speech and eye movements, CC due to degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCA15 is an autosomal dominant cerebellar CC ataxia (ADCA). It is very slow progressing form with a wide range of CC onset, ranging from childhood to adult. Most patients remain CC ambulatory. {ECO:0000269|PubMed:17590087, ECO:0000269|PubMed:18579805}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Spinocerebellar ataxia 29 (SCA29) [MIM:117360]: An autosomal CC dominant, congenital spinocerebellar ataxia characterized by early CC motor delay, hypotonia and mild cognitive delay. Affected individuals CC develop a very slowly progressive or non-progressive gait and limb CC ataxia associated with cerebellar atrophy on brain imaging. Additional CC variable features include nystagmus, dysarthria, and tremor. CC {ECO:0000269|PubMed:22986007, ECO:0000269|PubMed:26770814}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Gillespie syndrome (GLSP) [MIM:206700]: A rare disease CC characterized by bilateral iris hypoplasia, congenital hypotonia, non- CC progressive ataxia, progressive cerebellar atrophy, and intellectual CC disability. {ECO:0000269|PubMed:27108797, ECO:0000269|PubMed:27108798}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: Calcium appears to inhibit ligand binding to the CC receptor, most probably by interacting with a distinct calcium-binding CC protein which then inhibits the receptor. CC -!- SIMILARITY: Belongs to the InsP3 receptor family. {ECO:0000305}. CC -!- CAUTION: Alternative splice sites (AA 1053-1054) represent a non- CC canonical GA-AG donor-acceptor pair, but are well-supported by all CC available human transcripts, and by homologous transcripts in mouse, CC rat and cow. {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; D26070; BAA05065.1; -; mRNA. DR EMBL; L38019; AAB04947.2; -; mRNA. DR EMBL; U23850; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC018816; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC024168; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC069248; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC090944; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; S82269; AAD14386.1; -; mRNA. DR CCDS; CCDS46740.2; -. [Q14643-3] DR CCDS; CCDS54550.1; -. [Q14643-4] DR CCDS; CCDS54551.1; -. [Q14643-2] DR CCDS; CCDS93191.1; -. [Q14643-1] DR PIR; A55713; A55713. DR PIR; S54974; S54974. DR RefSeq; NP_001093422.2; NM_001099952.2. [Q14643-3] DR RefSeq; NP_001161744.1; NM_001168272.1. [Q14643-2] DR RefSeq; NP_002213.5; NM_002222.5. [Q14643-4] DR RefSeq; XP_011531985.1; XM_011533683.2. DR EMDB; EMD-20850; -. DR SMR; Q14643; -. DR BioGRID; 109913; 128. DR CORUM; Q14643; -. DR DIP; DIP-29714N; -. DR ELM; Q14643; -. DR IntAct; Q14643; 43. DR MINT; Q14643; -. DR STRING; 9606.ENSP00000306253; -. DR BindingDB; Q14643; -. DR ChEMBL; CHEMBL4046; -. DR DrugBank; DB03401; 1D-myo-inositol 1,4,5-trisphosphate. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB09462; Glycerin. DR DrugBank; DB11590; Thimerosal. DR TCDB; 1.A.3.2.6; the ryanodine-inositol 1,4,5-triphosphate receptor ca(2+) channel (rir-cac) family. DR GlyConnect; 1399; 1 N-Linked glycan (1 site). DR GlyCosmos; Q14643; 1 site, 1 glycan. DR GlyGen; Q14643; 3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (2 sites). DR iPTMnet; Q14643; -. DR PhosphoSitePlus; Q14643; -. DR SwissPalm; Q14643; -. DR BioMuta; ITPR1; -. DR DMDM; 519668682; -. DR EPD; Q14643; -. DR jPOST; Q14643; -. DR MassIVE; Q14643; -. DR MaxQB; Q14643; -. DR PaxDb; 9606-ENSP00000306253; -. DR PeptideAtlas; Q14643; -. DR ProteomicsDB; 17461; -. DR ProteomicsDB; 60081; -. [Q14643-1] DR ProteomicsDB; 60082; -. [Q14643-2] DR ProteomicsDB; 60083; -. [Q14643-3] DR ProteomicsDB; 60084; -. [Q14643-4] DR ProteomicsDB; 60085; -. [Q14643-5] DR ProteomicsDB; 60086; -. [Q14643-6] DR ProteomicsDB; 60087; -. [Q14643-7] DR ProteomicsDB; 60088; -. [Q14643-8] DR Pumba; Q14643; -. DR ABCD; Q14643; 1 sequenced antibody. DR Antibodypedia; 5503; 520 antibodies from 41 providers. DR DNASU; 3708; -. DR Ensembl; ENST00000357086.10; ENSP00000349597.4; ENSG00000150995.21. [Q14643-3] DR Ensembl; ENST00000443694.5; ENSP00000401671.2; ENSG00000150995.21. [Q14643-2] DR Ensembl; ENST00000456211.8; ENSP00000397885.2; ENSG00000150995.21. [Q14643-4] DR Ensembl; ENST00000648309.1; ENSP00000497026.1; ENSG00000150995.21. [Q14643-5] DR Ensembl; ENST00000649015.2; ENSP00000497605.1; ENSG00000150995.21. [Q14643-1] DR GeneID; 3708; -. DR KEGG; hsa:3708; -. DR MANE-Select; ENST00000649015.2; ENSP00000497605.1; NM_001378452.1; NP_001365381.1. DR UCSC; uc003bqc.3; human. [Q14643-1] DR AGR; HGNC:6180; -. DR CTD; 3708; -. DR DisGeNET; 3708; -. DR GeneCards; ITPR1; -. DR GeneReviews; ITPR1; -. DR HGNC; HGNC:6180; ITPR1. DR HPA; ENSG00000150995; Low tissue specificity. DR MalaCards; ITPR1; -. DR MIM; 117360; phenotype. DR MIM; 147265; gene. DR MIM; 206700; phenotype. DR MIM; 606658; phenotype. DR neXtProt; NX_Q14643; -. DR OpenTargets; ENSG00000150995; -. DR Orphanet; 1065; Aniridia-cerebellar ataxia-intellectual disability syndrome. DR Orphanet; 98769; Spinocerebellar ataxia type 15/16. DR Orphanet; 208513; Spinocerebellar ataxia type 29. DR PharmGKB; PA29978; -. DR VEuPathDB; HostDB:ENSG00000150995; -. DR eggNOG; KOG3533; Eukaryota. DR GeneTree; ENSGT00940000155071; -. DR HOGENOM; CLU_000206_1_0_1; -. DR InParanoid; Q14643; -. DR OMA; KMERVIF; -. DR OrthoDB; 5480299at2759; -. DR PhylomeDB; Q14643; -. DR TreeFam; TF312815; -. DR PathwayCommons; Q14643; -. 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-418457; cGMP effects. 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-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR SignaLink; Q14643; -. DR SIGNOR; Q14643; -. DR BioGRID-ORCS; 3708; 7 hits in 1155 CRISPR screens. DR ChiTaRS; ITPR1; human. DR GeneWiki; ITPR1; -. DR GenomeRNAi; 3708; -. DR Pharos; Q14643; Tchem. DR PRO; PR:Q14643; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q14643; Protein. DR Bgee; ENSG00000150995; Expressed in cauda epididymis and 190 other cell types or tissues. DR ExpressionAtlas; Q14643; baseline and differential. DR GO; GO:0005955; C:calcineurin complex; IEA:Ensembl. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005637; C:nuclear inner membrane; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0031088; C:platelet dense granule membrane; IDA:BHF-UCL. DR GO; GO:0031094; C:platelet dense tubular network; IDA:BHF-UCL. DR GO; GO:0031095; C:platelet dense tubular network membrane; TAS:Reactome. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0016529; C:sarcoplasmic reticulum; IBA:GO_Central. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0030667; C:secretory granule membrane; IBA:GO_Central. DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0019855; F:calcium channel inhibitor activity; IDA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0015085; F:calcium ion transmembrane transporter activity; TAS:ProtInc. DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB. DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IBA:GO_Central. DR GO; GO:0098695; F:inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels; IEA:Ensembl. DR GO; GO:0005220; F:inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; ISS:UniProtKB. DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0006816; P:calcium ion transport; NAS:UniProtKB. DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0042045; P:epithelial fluid transport; IEA:Ensembl. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB. DR GO; GO:0099105; P:ion channel modulating, G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:1990806; P:ligand-gated ion channel signaling pathway; IEA:Ensembl. DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; IDA:GO_Central. DR GO; GO:0007207; P:phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway; IEA:Ensembl. DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0010506; P:regulation of autophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR GO; GO:0050882; P:voluntary musculoskeletal movement; 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; IPR016024; ARM-type_fold. 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:SF2; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; 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; SSF48371; ARM repeat; 1. DR SUPFAM; SSF100909; IP3 receptor type 1 binding core, domain 2; 2. DR SUPFAM; SSF82109; MIR domain; 2. DR PROSITE; PS50919; MIR; 5. DR Genevisible; Q14643; HS. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Calcium; Calcium channel; KW Calcium transport; Cytoplasm; Cytoplasmic vesicle; Disease variant; KW Endoplasmic reticulum; Glycoprotein; Intellectual disability; Ion channel; KW Ion transport; Isopeptide bond; Ligand-gated ion channel; Lipoprotein; KW Membrane; Neurodegeneration; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Spinocerebellar ataxia; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation. FT CHAIN 1..2758 FT /note="Inositol 1,4,5-trisphosphate receptor type 1" FT /id="PRO_0000153920" FT TOPO_DOM 1..2282 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2283..2303 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2304..2314 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2315..2335 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2336..2361 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2362..2382 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2383..2405 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2406..2426 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2427..2448 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2449..2469 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2470..2577 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2578..2598 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2599..2758 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 112..166 FT /note="MIR 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 173..223 FT /note="MIR 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 231..287 FT /note="MIR 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 294..373 FT /note="MIR 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT DOMAIN 379..435 FT /note="MIR 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131" FT REGION 1015..1036 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1146..1178 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1708..1740 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1760..1796 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1890..1915 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1939..1960 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2472..2537 FT /note="Interaction with ERP44" FT /evidence="ECO:0000250" FT REGION 2729..2758 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1016..1033 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1155..1173 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 265..269 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000250" FT BINDING 508..511 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 482 FT /note="Phosphotyrosine" FT /evidence="ECO:0000255" FT MOD_RES 1598 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 1764 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2664 FT /note="Phosphotyrosine" FT /evidence="ECO:0000255" FT LIPID 56 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P11881" FT LIPID 850 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P11881" FT CARBOHYD 2512 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CROSSLNK 917 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 972 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1581 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1780 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1893 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1894 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1895 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1910 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1933 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 2127 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 2266 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT VAR_SEQ 322..336 FT /note="Missing (in isoform 2, isoform 4, isoform 5, isoform FT 7 and isoform 8)" FT /evidence="ECO:0000303|PubMed:7500840, FT ECO:0000303|PubMed:7945203, ECO:0000303|PubMed:8648241" FT /id="VSP_002687" FT VAR_SEQ 919..927 FT /note="Missing (in isoform 3, isoform 4, isoform 5 and FT isoform 8)" FT /evidence="ECO:0000303|PubMed:7852357, FT ECO:0000303|PubMed:7945203, ECO:0000303|PubMed:8648241" FT /id="VSP_002688" FT VAR_SEQ 1702..1724 FT /note="Missing (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:7852357, FT ECO:0000303|PubMed:7945203, ECO:0000303|PubMed:8648241" FT /id="VSP_002689" FT VAR_SEQ 1725..1740 FT /note="Missing (in isoform 3, isoform 4, isoform 6, isoform FT 7 and isoform 8)" FT /evidence="ECO:0000303|PubMed:7852357, FT ECO:0000303|PubMed:7945203, ECO:0000303|PubMed:8648241" FT /id="VSP_002690" FT VARIANT 602 FT /note="N -> D (in SCA29; dbSNP:rs397514536)" FT /evidence="ECO:0000269|PubMed:22986007" FT /id="VAR_069567" FT VARIANT 769 FT /note="M -> V (in dbSNP:rs35789999)" FT /id="VAR_037005" FT VARIANT 1083 FT /note="P -> L (in SCA15; dbSNP:rs121912425)" FT /evidence="ECO:0000269|PubMed:18579805" FT /id="VAR_081167" FT VARIANT 1430 FT /note="I -> V (in dbSNP:rs3749383)" FT /id="VAR_037006" FT VARIANT 1562 FT /note="V -> M (in SCA29; dbSNP:rs397514535)" FT /evidence="ECO:0000269|PubMed:22986007, FT ECO:0000269|PubMed:26770814" FT /id="VAR_069569" FT VARIANT 2109 FT /note="E -> Q (in GLSP)" FT /evidence="ECO:0000269|PubMed:27108798" FT /id="VAR_077462" FT VARIANT 2554 FT /note="G -> R (in GLSP; dbSNP:rs752281590)" FT /evidence="ECO:0000269|PubMed:27108798" FT /id="VAR_077463" FT VARIANT 2601 FT /note="F -> L (in GLSP; dbSNP:rs878853176)" FT /evidence="ECO:0000269|PubMed:27108797" FT /id="VAR_077464" FT VARIANT 2611 FT /note="Missing (in GLSP; alters calcium release of isoform FT 3; dbSNP:rs878853175)" FT /evidence="ECO:0000269|PubMed:27108797, FT ECO:0000269|PubMed:27108798" FT /id="VAR_077465" FT MUTAGEN 241 FT /note="R->Q: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 249 FT /note="K->Q: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 265 FT /note="R->Q: No effect on interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 267 FT /note="T->A: No effect on interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 269 FT /note="R->Q: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 504 FT /note="R->Q: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 506 FT /note="R->Q: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 508 FT /note="K->A: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 511 FT /note="R->A: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 567 FT /note="Y->A: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 568 FT /note="R->Q: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 569 FT /note="K->A: Abolishes interaction with AHCYL1." FT /evidence="ECO:0000269|PubMed:16793548" FT MUTAGEN 1059 FT /note="P->L: Creates a dileucine motif and recruits FT clathrin." FT /evidence="ECO:0000269|PubMed:30197081" FT CONFLICT 1557..1581 FT /note="AIAIPVDLDSQVNNLFLKSHSIVQK -> HCHSRGPGQPSQQPLSQVPQHCA FT E (in Ref. 6; AAD14386)" FT /evidence="ECO:0000305" FT CONFLICT 2302 FT /note="F -> L (in Ref. 2; AAB04947)" FT /evidence="ECO:0000305" FT CONFLICT 2305 FT /note="F -> L (in Ref. 2; AAB04947)" FT /evidence="ECO:0000305" FT CONFLICT 2448 FT /note="S -> A (in Ref. 4; U23850)" FT /evidence="ECO:0000305" SQ SEQUENCE 2758 AA; 313929 MW; D29B072252B0D8E7 CRC64; MSDKMSSFLH IGDICSLYAE GSTNGFISTL GLVDDRCVVQ PETGDLNNPP KKFRDCLFKL CPMNRYSAQK QFWKAAKPGA NSTTDAVLLN KLHHAADLEK KQNETENRKL LGTVIQYGNV IQLLHLKSNK YLTVNKRLPA LLEKNAMRVT LDEAGNEGSW FYIQPFYKLR SIGDSVVIGD KVVLNPVNAG QPLHASSHQL VDNPGCNEVN SVNCNTSWKI VLFMKWSDNK DDILKGGDVV RLFHAEQEKF LTCDEHRKKQ HVFLRTTGRQ SATSATSSKA LWEVEVVQHD PCRGGAGYWN SLFRFKHLAT GHYLAAEVDP DFEEECLEFQ PSVDPDQDAS RSRLRNAQEK MVYSLVSVPE GNDISSIFEL DPTTLRGGDS LVPRNSYVRL RHLCTNTWVH STNIPIDKEE EKPVMLKIGT SPVKEDKEAF AIVPVSPAEV RDLDFANDAS KVLGSIAGKL EKGTITQNER RSVTKLLEDL VYFVTGGTNS GQDVLEVVFS KPNRERQKLM REQNILKQIF KLLQAPFTDC GDGPMLRLEE LGDQRHAPFR HICRLCYRVL RHSQQDYRKN QEYIAKQFGF MQKQIGYDVL AEDTITALLH NNRKLLEKHI TAAEIDTFVS LVRKNREPRF LDYLSDLCVS MNKSIPVTQE LICKAVLNPT NADILIETKL VLSRFEFEGV SSTGENALEA GEDEEEVWLF WRDSNKEIRS KSVRELAQDA KEGQKEDRDV LSYYRYQLNL FARMCLDRQY LAINEISGQL DVDLILRCMS DENLPYDLRA SFCRLMLHMH VDRDPQEQVT PVKYARLWSE IPSEIAIDDY DSSGASKDEI KERFAQTMEF VEEYLRDVVC QRFPFSDKEK NKLTFEVVNL ARNLIYFGFY NFSDLLRLTK ILLAILDCVH VTTIFPISKM AKGEENKGNN DVEKLKSSNV MRSIHGVGEL MTQVVLRGGG FLPMTPMAAA PEGNVKQAEP EKEDIMVMDT KLKIIEILQF ILNVRLDYRI SCLLCIFKRE FDESNSQTSE TSSGNSSQEG PSNVPGALDF EHIEEQAEGI FGGSEENTPL DLDDHGGRTF LRVLLHLTMH DYPPLVSGAL QLLFRHFSQR QEVLQAFKQV QLLVTSQDVD NYKQIKQDLD QLRSIVEKSE LWVYKGQGPD ETMDGASGEN EHKKTEEGNN KPQKHESTSS YNYRVVKEIL IRLSKLCVQE SASVRKSRKQ QQRLLRNMGA HAVVLELLQI PYEKAEDTKM QEIMRLAHEF LQNFCAGNQQ NQALLHKHIN LFLNPGILEA VTMQHIFMNN FQLCSEINER VVQHFVHCIE THGRNVQYIK FLQTIVKAEG KFIKKCQDMV MAELVNSGED VLVFYNDRAS FQTLIQMMRS ERDRMDENSP LMYHIHLVEL LAVCTEGKNV YTEIKCNSLL PLDDIVRVVT HEDCIPEVKI AYINFLNHCY VDTEVEMKEI YTSNHMWKLF ENFLVDICRA CNNTSDRKHA DSILEKYVTE IVMSIVTTFF SSPFSDQSTT LQTRQPVFVQ LLQGVFRVYH CNWLMPSQKA SVESCIRVLS DVAKSRAIAI PVDLDSQVNN LFLKSHSIVQ KTAMNWRLSA RNAARRDSVL AASRDYRNII ERLQDIVSAL EDRLRPLVQA ELSVLVDVLH RPELLFPENT DARRKCESGG FICKLIKHTK QLLEENEEKL CIKVLQTLRE MMTKDRGYGE KLISIDELDN AELPPAPDSE NATEELEPSP PLRQLEDHKR GEALRQVLVN RYYGNVRPSG RRESLTSFGN GPLSAGGPGK PGGGGGGSGS SSMSRGEMSL AEVQCHLDKE GASNLVIDLI MNASSDRVFH ESILLAIALL EGGNTTIQHS FFCRLTEDKK SEKFFKVFYD RMKVAQQEIK ATVTVNTSDL GNKKKDDEVD RDAPSRKKAK EPTTQITEEV RDQLLEASAA TRKAFTTFRR EADPDDHYQP GEGTQATADK AKDDLEMSAV ITIMQPILRF LQLLCENHNR DLQNFLRCQN NKTNYNLVCE TLQFLDCICG STTGGLGLLG LYINEKNVAL INQTLESLTE YCQGPCHENQ NCIATHESNG IDIITALILN DINPLGKKRM DLVLELKNNA SKLLLAIMES RHDSENAERI LYNMRPKELV EVIKKAYMQG EVEFEDGENG EDGAASPRNV GHNIYILAHQ LARHNKELQS MLKPGGQVDG DEALEFYAKH TAQIEIVRLD RTMEQIVFPV PSICEFLTKE SKLRIYYTTE RDEQGSKIND FFLRSEDLFN EMNWQKKLRA QPVLYWCARN MSFWSSISFN LAVLMNLLVA FFYPFKGVRG GTLEPHWSGL LWTAMLISLA IVIALPKPHG IRALIASTIL RLIFSVGLQP TLFLLGAFNV CNKIIFLMSF VGNCGTFTRG YRAMVLDVEF LYHLLYLVIC AMGLFVHEFF YSLLLFDLVY REETLLNVIK SVTRNGRSII LTAVLALILV YLFSIVGYLF FKDDFILEVD RLPNETAVPE TGESLASEFL FSDVCRVESG ENCSSPAPRE ELVPAEETEQ DKEHTCETLL MCIVTVLSHG LRSGGGVGDV LRKPSKEEPL FAARVIYDLL FFFMVIIIVL NLIFGVIIDT FADLRSEKQK KEEILKTTCF ICGLERDKFD NKTVTFEEHI KEEHNMWHYL CFIVLVKVKD STEYTGPESY VAEMIKERNL DWFPRMRAMS LVSSDSEGEQ NELRNLQEKL ESTMKLVTNL SGQLSELKDQ MTEQRKQKQR IGLLGHPPHM NVNPQQPA //