ITPR1_HUMAN
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 03-AUG-2022, entry version 232.
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}.
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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 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 SMR; Q14643; -.
DR BioGRID; 109913; 115.
DR CORUM; Q14643; -.
DR DIP; DIP-29714N; -.
DR ELM; Q14643; -.
DR IntAct; Q14643; 41.
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 GlyGen; Q14643; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
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; Q14643; -.
DR PeptideAtlas; Q14643; -.
DR PRIDE; 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 ABCD; Q14643; 1 sequenced antibody.
DR Antibodypedia; 5503; 421 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 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; GLIDKTW; -.
DR OrthoDB; 94996at2759; -.
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; 6 hits in 1073 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 188 other tissues.
DR ExpressionAtlas; Q14643; baseline and differential.
DR Genevisible; Q14643; HS.
DR GO; GO:0005955; C:calcineurin complex; IEA:Ensembl.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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: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:0050849; P:negative regulation of calcium-mediated signaling; IDA:GO_Central.
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 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; IPR035910; RyR/IP3R_RIH_dom_sf.
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; SSF100909; 2.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50919; MIR; 5.
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
