ID ITPR1_MOUSE Reviewed; 2749 AA. AC P11881; P20943; Q99LG5; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 2. DT 02-OCT-2024, entry version 245. DE RecName: Full=Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 {ECO:0000305}; DE AltName: Full=IP3 receptor isoform 1; DE Short=IP3R 1; DE Short=InsP3R1 {ECO:0000250|UniProtKB:Q14643}; DE AltName: Full=Inositol 1,4,5 trisphosphate receptor {ECO:0000303|PubMed:1648733}; DE AltName: Full=Inositol 1,4,5-trisphosphate receptor type 1 {ECO:0000303|PubMed:15652484}; DE AltName: Full=Inositol 1,4,5-trisphosphate-binding protein P400 {ECO:0000303|PubMed:2554142}; DE AltName: Full=Protein PCD-6 {ECO:0000305|PubMed:3199205}; DE AltName: Full=Purkinje cell protein 1; DE AltName: Full=Type 1 inositol 1,4,5-trisphosphate receptor {ECO:0000303|PubMed:11955285}; DE Short=Type 1 InsP3 receptor; GN Name=Itpr1 {ECO:0000312|MGI:MGI:96623}; GN Synonyms=Insp3r {ECO:0000303|PubMed:1648733}, GN Pcd6 {ECO:0000303|PubMed:3199205}, Pcp1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RC TISSUE=Purkinje cell; RX PubMed=2554142; DOI=10.1038/342032a0; RA Furuichi T., Yoshikawa S., Miyawaki A., Wada K., Maeda N., Mikoshiba K.; RT "Primary structure and functional expression of the inositol 1,4,5- RT trisphosphate-binding protein P400."; RL Nature 342:32-38(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=ICR; TISSUE=Cerebellum; RX PubMed=2762133; DOI=10.1093/nar/17.13.5385; RA Furuichi T., Yoshikawa S., Mikoshiba K.; RT "Nucleotide sequence of cDNA encoding P400 protein in the mouse RT cerebellum."; RL Nucleic Acids Res. 17:5385-5386(1989). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 318-332 AND 1692-1731, AND ALTERNATIVE RP SPLICING. RC STRAIN=ICR; RX PubMed=1648733; DOI=10.1073/pnas.88.14.6244; RA Nakagawa T., Okano H., Furuichi T., Aruga J., Mikoshiba K.; RT "The subtypes of the mouse inositol 1,4,5-trisphosphate receptor are RT expressed in a tissue-specific and developmentally specific manner."; RL Proc. Natl. Acad. Sci. U.S.A. 88:6244-6248(1991). RN [5] RP PROTEIN SEQUENCE OF 862-871, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain; RA Lubec G., Kang S.U.; RL Submitted (APR-2007) to UniProtKB. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2098-2749. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2250-2749. RC STRAIN=C57BL/6J; TISSUE=Cerebellum; RX PubMed=3199205; DOI=10.1523/jneurosci.08-12-04780.1988; RA Nordquist D.T., Kozak C.A., Orr H.T.; RT "cDNA cloning and characterization of three genes uniquely expressed in RT cerebellum by Purkinje neurons."; RL J. Neurosci. 8:4780-4789(1988). RN [8] RP INTERACTION WITH CALM1. RX PubMed=10620513; DOI=10.1042/bj3450357; RA Adkins C.E., Morris S.A., De Smedt H., Sienaert I., Toeroek K., RA Taylor C.W.; RT "Ca2+-calmodulin inhibits Ca2+ release mediated by type-1, -2 and -3 RT inositol trisphosphate receptors."; RL Biochem. J. 345:357-363(2000). RN [9] RP FUNCTION, TRANSPORTER ACTIVITY, AND INTERACTION WITH CALM1. RX PubMed=11955285; DOI=10.1042/bj20020144; RA Sienaert I., Nadif Kasri N., Vanlingen S., Parys J.B., Callewaert G., RA Missiaen L., de Smedt H.; RT "Localization and function of a calmodulin-apocalmodulin-binding domain in RT the N-terminal part of the type 1 inositol 1,4,5-trisphosphate receptor."; RL Biochem. J. 365:269-277(2002). RN [10] RP INTERACTION WITH AHCYL1. RX PubMed=12525476; DOI=10.1074/jbc.m210119200; RA Ando H., Mizutani A., Matsu-ura T., Mikoshiba K.; RT "IRBIT, a novel inositol 1,4,5-trisphosphate (IP3) receptor-binding RT protein, is released from the IP3 receptor upon IP3 binding to the RT receptor."; RL J. Biol. Chem. 278:10602-10612(2003). RN [11] RP INTERACTION WITH ERP44, AND MUTAGENESIS OF CYS-2496; CYS-2504 AND CYS-2527. 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 [12] RP INTERACTION WITH AHCYL1. RX PubMed=16527252; DOI=10.1016/j.bbrc.2006.02.119; RA Devogelaere B., Nadif Kasri N., Derua R., Waelkens E., Callewaert G., RA Missiaen L., Parys J.B., De Smedt H.; RT "Binding of IRBIT to the IP3 receptor: determinants and functional RT effects."; RL Biochem. Biophys. Res. Commun. 343:49-56(2006). RN [13] 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1588, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200; RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.; RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and RT MS/MS/MS."; RL Mol. Cell. Proteomics 6:669-676(2007). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1588, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18630941; DOI=10.1021/pr800223m; RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.; RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity RT chromatography adsorbent for phosphoproteome analysis."; RL J. Proteome Res. 7:3957-3967(2008). RN [16] RP FUNCTION. RX PubMed=19752026; DOI=10.1083/jcb.200904060; RA Li G., Mongillo M., Chin K.T., Harding H., Ron D., Marks A.R., Tabas I.; RT "Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate RT receptor activity in endoplasmic reticulum stress-induced apoptosis."; RL J. Cell Biol. 186:783-792(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1588, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, RC Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [18] RP FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF TYR-167; LYS-168 AND RP LEU-169. RX PubMed=20813840; DOI=10.1074/jbc.m110.140129; RA Yamazaki H., Chan J., Ikura M., Michikawa T., Mikoshiba K.; RT "Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates RT functional coupling between ligand binding and channel opening."; RL J. Biol. Chem. 285:36081-36091(2010). RN [19] 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 [20] RP INTERACTION WITH AHCYL1, MUTAGENESIS OF SER-1588 AND SER-1755, RP PHOSPHORYLATION, AND FUNCTION. RX PubMed=23542070; DOI=10.1053/j.gastro.2013.03.047; RA Park S., Shcheynikov N., Hong J.H., Zheng C., Suh S.H., Kawaai K., Ando H., RA Mizutani A., Abe T., Kiyonari H., Seki G., Yule D., Mikoshiba K., RA Muallem S.; RT "Irbit mediates synergy between ca(2+) and cAMP signaling pathways during RT epithelial transport in mice."; RL Gastroenterology 145:232-241(2013). RN [21] 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 [22] RP SUBCELLULAR LOCATION. RX PubMed=24374158; DOI=10.1016/j.ydbio.2013.12.025; RA Kim B., Zhang X., Kan R., Cohen R., Mukai C., Travis A.J., Coonrod S.A.; RT "The role of MATER in endoplasmic reticulum distribution and calcium RT homeostasis in mouse oocytes."; RL Dev. Biol. 386:331-339(2014). RN [23] RP PALMITOYLATION AT CYS-56 AND CYS-849, AND MUTAGENESIS OF CYS-56; CYS-849 RP AND CYS-2215. RX PubMed=25368151; DOI=10.1073/pnas.1417176111; RA Fredericks G.J., Hoffmann F.W., Rose A.H., Osterheld H.J., Hess F.M., RA Mercier F., Hoffmann P.R.; RT "Stable expression and function of the inositol 1,4,5-triphosphate receptor RT requires palmitoylation by a DHHC6/selenoprotein K complex."; RL Proc. Natl. Acad. Sci. U.S.A. 111:16478-16483(2014). RN [24] RP FUNCTION, AND INTERACTION WITH HSPA9. RX PubMed=29907098; DOI=10.1186/s12882-018-0940-3; RA Xu H., Guan N., Ren Y.L., Wei Q.J., Tao Y.H., Yang G.S., Liu X.Y., Bu D.F., RA Zhang Y., Zhu S.N.; RT "IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes RT from apoptosis and decrease proteinuria in an Adriamycin nephropathy rat RT model."; RL BMC Nephrol. 19:140-140(2018). RN [25] RP FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, INTERACTION WITH ERLIN1; ERLIN2 RP AND RNF170, MUTAGENESIS OF 2463-LYS-ASP-2464; 2464-ASP-ASP-2465; RP 2465-ASP--ILE-2467; ASP-2465; 2468-LEU--VAL-2470; ASP-2471; RP 2471-ASP-ARG-2472; ARG-2472; ASP-2550 AND ARG-2596, AND POLYUBIQUITINATION. RX PubMed=35568199; DOI=10.1016/j.jbc.2022.102026; RA Gao X., Bonzerato C.G., Wojcikiewicz R.J.H.; RT "Binding of the erlin1/2 complex to the third intralumenal loop of IP3R1 RT triggers its ubiquitin-proteasomal degradation."; RL J. Biol. Chem. 298:102026-102026(2022). RN [26] RP FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=38099643; DOI=10.7554/elife.88082; RA Akizawa H., Lopes E.M., Fissore R.A.; RT "Zn2+ is essential for Ca2+ oscillations in mouse eggs."; RL Elife 12:0-0(2023). RN [27] {ECO:0007744|PDB:1N4K} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 224-604 IN COMPLEX WITH INOSITOL RP 1,4,5-TRISPHOSPHATE, AND MUTAGENESIS OF THR-267 AND TYR-567. RX PubMed=12442173; DOI=10.1038/nature01268; RA Bosanac I., Alattia J.R., Mal T.K., Chan J., Talarico S., Tong F.K., RA Tong K.I., Yoshikawa F., Furuichi T., Iwai M., Michikawa T., Mikoshiba K., RA Ikura M.; RT "Structure of the inositol 1,4,5-trisphosphate receptor binding core in RT complex with its ligand."; RL Nature 420:696-700(2002). RN [28] {ECO:0007744|PDB:1XZZ} RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 2-223. RX PubMed=15664189; DOI=10.1016/j.molcel.2004.11.047; RA Bosanac I., Yamazaki H., Matsu-Ura T., Michikawa T., Mikoshiba K., RA Ikura M.; RT "Crystal structure of the ligand binding suppressor domain of type 1 RT inositol 1,4,5-trisphosphate receptor."; RL Mol. Cell 17:193-203(2005). RN [29] {ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5X9Z, ECO:0007744|PDB:5XA0, ECO:0007744|PDB:5XA1} RP X-RAY CRYSTALLOGRAPHY (5.81 ANGSTROMS) OF 1-1581 IN COMPLEX WITH RP D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE, FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, RP AND SUBCELLULAR LOCATION. RX PubMed=28416699; DOI=10.1073/pnas.1701420114; RA Hamada K., Miyatake H., Terauchi A., Mikoshiba K.; RT "IP3-mediated gating mechanism of the IP3 receptor revealed by mutagenesis RT and X-ray crystallography."; RL Proc. Natl. Acad. Sci. U.S.A. 114:4661-4666(2017). CC -!- FUNCTION: Inositol 1,4,5-trisphosphate-gated calcium channel that, upon CC inositol 1,4,5-trisphosphate binding, mediates calcium release from the CC endoplasmic reticulum (ER) and participates in calcium oscillations CC (PubMed:11955285, PubMed:12442173, PubMed:20813840, PubMed:2554142, CC PubMed:28416699, PubMed:35568199, PubMed:38099643). Undergoes CC conformational changes upon ligand binding, suggesting structural CC flexibility that allows the channel to switch from a closed state, CC capable of interacting with its ligands such as inositol 1,4,5- CC trisphosphate and Ca(2+), to an open state, capable of transferring CC calcium ions across the ER membrane (By similarity). Cytoplasmic CC calcium, released from the ER, triggers apoptosis by the activation of CC CAMK2 complex (PubMed:19752026). Part of a complex composed of HSPA9, CC ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent CC apoptosis by facilitating calcium transport from the ER lumen to the CC mitochondria intermembrane space thus providing calcium for the CC downstream calcium channel MCU that directly releases it into CC mitochondria matrix (PubMed:29907098). Involved in the regulation of CC epithelial secretion of electrolytes and fluid through the interaction CC with AHCYL1 (PubMed:23542070). Regulates fertilization and egg CC activation by tuning the frequency and amplitude of calcium CC oscillations (PubMed:38099643). {ECO:0000250|UniProtKB:P29994, CC ECO:0000269|PubMed:11955285, ECO:0000269|PubMed:12442173, CC ECO:0000269|PubMed:19752026, ECO:0000269|PubMed:20813840, CC ECO:0000269|PubMed:23542070, ECO:0000269|PubMed:2554142, CC ECO:0000269|PubMed:28416699, ECO:0000269|PubMed:29907098, CC ECO:0000269|PubMed:35568199, ECO:0000269|PubMed:38099643}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:11955285, CC ECO:0000269|PubMed:20813840, ECO:0000269|PubMed:28416699, CC ECO:0000269|PubMed:35568199, ECO:0000269|PubMed:38099643}; CC -!- ACTIVITY REGULATION: Inositol 1,4,5-trisphosphate-gated calcium channel CC activity is regulated by cytosolic calcium in a biphasic manner, with CC low concentrations causing activation and higher concentrations CC inhibiting channel opening, giving rise to calcium oscillations. ATP CC increases the open probability of IP3R1 by synergizing with the CC activating effect of these two primarily ligands, inositol 1,4,5- CC trisphosphate and calcium (By similarity). Inositol 1,4,5- CC trisphosphate-gated calcium channel activity is activated by zinc ions CC (PubMed:38099643). Inositol 1,4,5-trisphosphate-gated calcium channel CC activity is inhibited by CALM1 in a calcium-dependent manner (By CC similarity). {ECO:0000250|UniProtKB:P29994, CC ECO:0000250|UniProtKB:Q14643, ECO:0000269|PubMed:38099643}. CC -!- SUBUNIT: Homodimer (PubMed:28416699). Homotetramer (PubMed:35568199). CC Interacts with ERP44 in a pH-, redox state- and calcium-dependent CC manner which results in the inhibition the calcium channel activity CC (PubMed:15652484). The strength of this interaction inversely CC correlates with calcium concentration (PubMed:15652484). Part of cGMP CC kinase signaling complex at least composed of ACTA2/alpha-actin, CC CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1 (By similarity). CC Interacts with IRAG1 (PubMed:16990611). Interacts with CABP1 (via N- CC terminus) (By similarity). Interacts with TESPA1 (PubMed:23650607). CC Interacts (when not phosphorylated) with AHCYL1 (when phosphorylated); CC the interaction suppresses inositol 1,4,5-trisphosphate binding to CC ITPR1 and is increased in the presence of BCL2L10 (PubMed:12525476, CC PubMed:16527252, PubMed:23542070). Interacts with AHCYL2 (with lower CC affinity than with AHCYL1). Interacts with BCL2L10; the interaction is CC increased in the presence of AHCLY1 (By similarity). Interacts with BOK CC (via BH4 domain); protects ITPR1 from proteolysis by CASP3 during CC apoptosis (PubMed:23884412). Interacts with TRPC4 (By similarity). CC Interacts with CHGA and CHGB (By similarity). Interacts with CALM1; CC this interaction inhibits inositol 1,4,5 trisphosphate binding in both CC the presence and absence of calcium and Inositol 1,4,5-trisphosphate- CC induced calcium release in the presence of calcium (PubMed:10620513, CC PubMed:11955285). Interacts with the complex composed by ERLIN1, ERLIN2 CC and RNF170 through ERLIN2; this interaction triggers its ubiquitin- CC proteasomal degradation (PubMed:35568199). Interacts with HSPA9; this CC interaction couples ITPR1 to VDAC1 (By similarity). CC {ECO:0000250|UniProtKB:P29994, ECO:0000250|UniProtKB:Q14643, CC ECO:0000250|UniProtKB:Q9TU34, ECO:0000269|PubMed:10620513, CC ECO:0000269|PubMed:11955285, ECO:0000269|PubMed:12525476, CC ECO:0000269|PubMed:15652484, ECO:0000269|PubMed:16527252, CC ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:23542070, CC ECO:0000269|PubMed:23650607, ECO:0000269|PubMed:23884412, CC ECO:0000269|PubMed:28416699, ECO:0000269|PubMed:35568199}. CC -!- INTERACTION: CC P11881; Q8VDN2: Atp1a1; NbExp=3; IntAct=EBI-541478, EBI-444536; CC P11881; Q6PIE5: Atp1a2; NbExp=3; IntAct=EBI-541478, EBI-6665421; CC P11881; Q9D1Q6: Erp44; NbExp=5; IntAct=EBI-541478, EBI-541567; CC P11881; O35157: Slc8a1; NbExp=4; IntAct=EBI-541478, EBI-8351080; CC P11881; P10415: BCL2; Xeno; NbExp=3; IntAct=EBI-541478, EBI-77694; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:28416699, ECO:0000305|PubMed:24374158, CC ECO:0000305|PubMed:25368151}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P29994, ECO:0000255}. Cytoplasmic vesicle, CC secretory vesicle membrane {ECO:0000250|UniProtKB:Q9TU34}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:P29994, ECO:0000255}. CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q14643}. CC Note=Found in a complex with HSPA9 and VDAC1 at the endoplasmic CC reticulum-mitochondria contact sites. {ECO:0000250|UniProtKB:P29994, CC ECO:0000250|UniProtKB:Q9TU34}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Comment=There is a combination of two alternatively spliced domains CC at site SI and site SII (A, B and C). Experimental confirmation may CC be lacking for some isoforms.; CC Name=1; Synonyms=SISIIABC; CC IsoId=P11881-1; Sequence=Displayed; CC Name=2; Synonyms=SI-SIIABC; CC IsoId=P11881-2; Sequence=VSP_002691; CC Name=3; Synonyms=SISIIAC; CC IsoId=P11881-3; Sequence=VSP_002693; CC Name=4; Synonyms=SI-SIIAC; CC IsoId=P11881-4; Sequence=VSP_002691, VSP_002693; CC Name=5; Synonyms=SISIIA; CC IsoId=P11881-5; Sequence=VSP_002693, VSP_002694; CC Name=6; Synonyms=SI-SIIA; CC IsoId=P11881-6; Sequence=VSP_002691, VSP_002693, VSP_002694; CC Name=7; Synonyms=SISII; CC IsoId=P11881-7; Sequence=VSP_002692, VSP_002693, VSP_002694; CC Name=8; Synonyms=SI-SII; CC IsoId=P11881-8; Sequence=VSP_002691, VSP_002692, VSP_002693, CC VSP_002694; CC -!- DOMAIN: The ITPR1 structure has a large solenoid CY assembly built CC around the central helical bundle made of the C-terminal domains from CC four IP3R1 subunits. The solenoid scaffold includes domains responsible CC for binding of ligands and regulatory proteins and is connected via an CC allosteric nexus at the cytosolic-membrane interface to the CC transmembrane channel assembly. Six transmembrane helices from each CC subunit form the central ion-conduction pore. CC {ECO:0000250|UniProtKB:P29994}. CC -!- PTM: Polyubiquitinated (PubMed:35568199). Polyubiquitination targets CC ITPR1 for proteasomal degradation (PubMed:35568199). Approximately 40% CC of the ITPR1-associated ubiquitin is monoubiquitin, and polyubiquitins CC are both 'Lys-48'- and 'Lys-63'-linked (By similarity). CC {ECO:0000250|UniProtKB:P29994, ECO:0000269|PubMed:35568199}. CC -!- PTM: Phosphorylation by cAMP kinase (PKA) enhances calcium release (By CC similarity). Phosphorylation by PKA increases the interaction with CC inositol 1,4,5-trisphosphate and decreases the interaction with AHCYL1 CC (Probable). {ECO:0000250|UniProtKB:P29994, CC ECO:0000305|PubMed:23542070}. CC -!- PTM: Phosphorylated on tyrosine residues. CC {ECO:0000250|UniProtKB:Q14643}. CC -!- PTM: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of CC ITPR1 stability and function (PubMed:25368151). CC {ECO:0000269|PubMed:25368151}. CC -!- SIMILARITY: Belongs to the InsP3 receptor family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA88319.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH03271.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; X15373; CAA33433.1; -; mRNA. DR EMBL; AC120411; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC153986; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC156506; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; M75986; AAA39316.1; -; Genomic_DNA. DR EMBL; M75987; AAA39317.1; -; Genomic_DNA. DR EMBL; BC003271; AAH03271.1; ALT_INIT; mRNA. DR EMBL; M21530; AAA88319.1; ALT_INIT; mRNA. DR CCDS; CCDS51869.1; -. [P11881-1] DR PIR; S04844; ACMSIT. DR RefSeq; NP_034715.3; NM_010585.5. [P11881-1] DR RefSeq; XP_006505693.1; XM_006505630.1. [P11881-2] DR RefSeq; XP_006505699.1; XM_006505636.1. [P11881-7] DR RefSeq; XP_006505700.1; XM_006505637.1. [P11881-8] DR RefSeq; XP_017176897.1; XM_017321408.1. [P11881-3] DR RefSeq; XP_017176899.1; XM_017321410.1. [P11881-4] DR PDB; 1N4K; X-ray; 2.20 A; A=224-604. DR PDB; 1XZZ; X-ray; 1.80 A; A=2-223. DR PDB; 5GUG; X-ray; 7.40 A; A/B=1-2217. DR PDB; 5X9Z; X-ray; 7.31 A; A/B=1-2217. DR PDB; 5XA0; X-ray; 5.81 A; A/B=1-1581. DR PDB; 5XA1; X-ray; 6.20 A; A/B=1-1581. DR PDBsum; 1N4K; -. DR PDBsum; 1XZZ; -. DR PDBsum; 5GUG; -. DR PDBsum; 5X9Z; -. DR PDBsum; 5XA0; -. DR PDBsum; 5XA1; -. DR SASBDB; P11881; -. DR SMR; P11881; -. DR BioGRID; 200847; 43. DR CORUM; P11881; -. DR DIP; DIP-32243N; -. DR IntAct; P11881; 21. DR MINT; P11881; -. DR STRING; 10090.ENSMUSP00000032192; -. DR GlyConnect; 2438; 14 N-Linked glycans (1 site). [P11881-3] DR GlyGen; P11881; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11881; -. DR PhosphoSitePlus; P11881; -. DR SwissPalm; P11881; -. DR jPOST; P11881; -. DR PaxDb; 10090-ENSMUSP00000032192; -. DR PeptideAtlas; P11881; -. DR ProteomicsDB; 269006; -. [P11881-1] DR ProteomicsDB; 269007; -. [P11881-2] DR ProteomicsDB; 269008; -. [P11881-3] DR ProteomicsDB; 269009; -. [P11881-4] DR ProteomicsDB; 269010; -. [P11881-5] DR ProteomicsDB; 269011; -. [P11881-6] DR ProteomicsDB; 269012; -. [P11881-7] DR ProteomicsDB; 269013; -. [P11881-8] DR Pumba; P11881; -. DR ABCD; P11881; 1 sequenced antibody. DR Antibodypedia; 5503; 507 antibodies from 41 providers. DR DNASU; 16438; -. DR Ensembl; ENSMUST00000032192.9; ENSMUSP00000032192.7; ENSMUSG00000030102.12. [P11881-1] DR Ensembl; ENSMUST00000203615.3; ENSMUSP00000144880.2; ENSMUSG00000030102.12. [P11881-3] DR GeneID; 16438; -. DR KEGG; mmu:16438; -. DR UCSC; uc033itt.1; mouse. [P11881-1] DR AGR; MGI:96623; -. DR CTD; 3708; -. DR MGI; MGI:96623; Itpr1. DR VEuPathDB; HostDB:ENSMUSG00000030102; -. DR eggNOG; KOG3533; Eukaryota. DR GeneTree; ENSGT00940000155071; -. DR HOGENOM; CLU_000206_1_0_1; -. DR InParanoid; P11881; -. DR OMA; KMERVIF; -. DR OrthoDB; 5480299at2759; -. DR PhylomeDB; P11881; -. DR TreeFam; TF312815; -. DR Reactome; R-MMU-114508; Effects of PIP2 hydrolysis. DR Reactome; R-MMU-139853; Elevation of cytosolic Ca2+ levels. DR Reactome; R-MMU-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion. DR Reactome; R-MMU-418457; cGMP effects. DR Reactome; R-MMU-5578775; Ion homeostasis. DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR BioGRID-ORCS; 16438; 1 hit in 78 CRISPR screens. DR ChiTaRS; Itpr1; mouse. DR EvolutionaryTrace; P11881; -. DR PRO; PR:P11881; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; P11881; protein. DR Bgee; ENSMUSG00000030102; Expressed in cerebellar vermis and 268 other cell types or tissues. DR ExpressionAtlas; P11881; baseline and differential. DR GO; GO:0005955; C:calcineurin complex; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI. DR GO; GO:0016020; C:membrane; ISO:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005635; C:nuclear envelope; IDA:MGI. DR GO; GO:0005637; C:nuclear inner membrane; IDA:MGI. DR GO; GO:0005730; C:nucleolus; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0031088; C:platelet dense granule membrane; IEA:Ensembl. DR GO; GO:0031094; C:platelet dense tubular network; IEA:Ensembl. DR GO; GO:0098794; C:postsynapse; ISO:MGI. DR GO; GO:0014069; C:postsynaptic density; IDA:MGI. DR GO; GO:0098793; C:presynapse; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; IPI:MGI. DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO. DR GO; GO:0030667; C:secretory granule membrane; IBA:GO_Central. DR GO; GO:0030868; C:smooth endoplasmic reticulum membrane; ISO:MGI. DR GO; GO:0045202; C:synapse; IPI:MGI. DR GO; GO:0097060; C:synaptic membrane; ISO:MGI. DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019855; F:calcium channel inhibitor activity; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IDA:UniProtKB. DR GO; GO:0098695; F:inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels; IDA:SynGO. DR GO; GO:0005220; F:inositol 1,4,5-trisphosphate-gated calcium channel activity; IDA:UniProtKB. DR GO; GO:0015278; F:intracellularly gated calcium channel activity; IDA:UniProtKB. DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IPI:MGI. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI. DR GO; GO:0036444; P:calcium import into the mitochondrion; ISS:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IDA:MGI. DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI. DR GO; GO:0071320; P:cellular response to cAMP; ISO:MGI. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IGI:MGI. DR GO; GO:0042045; P:epithelial fluid transport; IDA:UniProtKB. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:UniProtKB. DR GO; GO:0099105; P:ion channel modulating, G protein-coupled receptor signaling pathway; IMP:MGI. DR GO; GO:1990806; P:ligand-gated ion channel signaling pathway; IMP:MGI. DR GO; GO:0097421; P:liver regeneration; ISO:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI. DR GO; GO:0050849; P:negative regulation of calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0007207; P:phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway; IGI:MGI. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IMP:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISO:MGI. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISO:MGI. DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:MGI. DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI. DR GO; GO:0009791; P:post-embryonic development; IMP:MGI. DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:UniProtKB. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB. DR GO; GO:1903514; P:release of sequestered calcium ion into cytosol by endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL. DR GO; GO:0007338; P:single fertilization; IDA:UniProtKB. DR GO; GO:0050882; P:voluntary musculoskeletal movement; IMP:MGI. 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: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; 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; Alternative splicing; Apoptosis; ATP-binding; Calcium; KW Calcium channel; Calcium transport; Cytoplasm; Cytoplasmic vesicle; KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; KW Ion channel; Ion transport; Isopeptide bond; Ligand-gated ion channel; KW Lipoprotein; Membrane; Metal-binding; Nucleotide-binding; Palmitate; KW Phosphoprotein; Receptor; Reference proteome; Repeat; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation; Zinc. FT CHAIN 1..2749 FT /note="Inositol 1,4,5-trisphosphate-gated calcium channel FT ITPR1" FT /id="PRO_0000153921" FT TOPO_DOM 1..2273 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TRANSMEM 2274..2294 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TOPO_DOM 2295..2305 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TRANSMEM 2306..2326 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TOPO_DOM 2327..2352 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TRANSMEM 2353..2373 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TOPO_DOM 2374..2396 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TRANSMEM 2397..2417 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TOPO_DOM 2418..2439 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TRANSMEM 2440..2460 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TOPO_DOM 2461..2569 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TRANSMEM 2570..2590 FT /note="Helical" FT /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255" FT TOPO_DOM 2591..2749 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P29994, 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 1005..1026 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1136..1167 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1695..1730 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1751..1788 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1881..1906 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1932..1952 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2463..2528 FT /note="Interaction with ERP44" FT /evidence="ECO:0000269|PubMed:15652484" FT REGION 2721..2749 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1006..1023 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1145..1163 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1705..1719 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 265 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0000269|PubMed:28416699, ECO:0007744|PDB:1N4K, FT ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5XA1" FT BINDING 267 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0000269|PubMed:28416699, ECO:0007744|PDB:1N4K, FT ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5XA1" FT BINDING 268 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0000269|PubMed:28416699, ECO:0007744|PDB:1N4K, FT ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5XA1" FT BINDING 269 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0000269|PubMed:28416699, ECO:0007744|PDB:1N4K, FT ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5XA1" FT BINDING 508 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0000269|PubMed:28416699, ECO:0007744|PDB:1N4K, FT ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5XA1" FT BINDING 511 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0007744|PDB:1N4K" FT BINDING 567 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0000269|PubMed:28416699, ECO:0007744|PDB:1N4K, FT ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5XA1" FT BINDING 568 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT /evidence="ECO:0000269|PubMed:12442173, FT ECO:0000269|PubMed:28416699, ECO:0007744|PDB:1N4K, FT ECO:0007744|PDB:5GUG, ECO:0007744|PDB:5XA1" FT BINDING 747 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="low affinity" FT /evidence="ECO:0000250|UniProtKB:Q14573" FT BINDING 1127 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="low affinity" FT /evidence="ECO:0000250|UniProtKB:Q14573" FT BINDING 1130 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="low affinity" FT /evidence="ECO:0000250|UniProtKB:Q14573" FT BINDING 1977 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="high affinity" FT /evidence="ECO:0000250|UniProtKB:Q14573" FT BINDING 2041 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="high affinity" FT /evidence="ECO:0000250|UniProtKB:Q14573" FT BINDING 2220 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2223 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2610 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2610 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2611 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2613 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2630 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2635 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2635 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2637 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P29994" FT BINDING 2653 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="high affinity" FT /evidence="ECO:0000250|UniProtKB:Q14573" FT MOD_RES 1588 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17208939, FT ECO:0007744|PubMed:18630941, ECO:0007744|PubMed:21183079" FT MOD_RES 1755 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250|UniProtKB:P29994" FT LIPID 56 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:25368151" FT LIPID 849 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:25368151" FT DISULFID 2527..2533 FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 916 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 962 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1571 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1771 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1884 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1885 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1886 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1901 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 1924 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 2118 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT CROSSLNK 2257 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P29994" FT VAR_SEQ 318..332 FT /note="Missing (in isoform 2, isoform 4, isoform 6 and FT isoform 8)" FT /evidence="ECO:0000305" FT /id="VSP_002691" FT VAR_SEQ 1692..1714 FT /note="Missing (in isoform 7 and isoform 8)" FT /evidence="ECO:0000305" FT /id="VSP_002692" FT VAR_SEQ 1715 FT /note="Missing (in isoform 3, isoform 4, isoform 5, isoform FT 6, isoform 7 and isoform 8)" FT /evidence="ECO:0000305" FT /id="VSP_002693" FT VAR_SEQ 1716..1731 FT /note="Missing (in isoform 5, isoform 6, isoform 7 and FT isoform 8)" FT /evidence="ECO:0000305" FT /id="VSP_002694" FT MUTAGEN 56 FT /note="C->A: Strongly reduced palmitoylation; when FT associated with A-849 and A-2215." FT /evidence="ECO:0000269|PubMed:25368151" FT MUTAGEN 167 FT /note="Y->A: Nearly abolishes calcium flux." FT /evidence="ECO:0000269|PubMed:20813840" FT MUTAGEN 168 FT /note="K->A: Reduces calcium flux by about 50%." FT /evidence="ECO:0000269|PubMed:20813840" FT MUTAGEN 169 FT /note="L->A: Reduces calcium flux by about 50%." FT /evidence="ECO:0000269|PubMed:20813840" FT MUTAGEN 267 FT /note="T->A: Abolishes inositol 1,4,5-triphosphate FT binding." FT /evidence="ECO:0000269|PubMed:12442173" FT MUTAGEN 567 FT /note="Y->A,F: Abolishes inositol 1,4,5-triphosphate FT binding." FT /evidence="ECO:0000269|PubMed:12442173" FT MUTAGEN 849 FT /note="C->A: Strongly reduced palmitoylation; when FT associated with A-56 and A-2215." FT /evidence="ECO:0000269|PubMed:25368151" FT MUTAGEN 1588 FT /note="S->A: Increases interaction with AHCYL1; when FT associated with A-1755." FT /evidence="ECO:0000269|PubMed:23542070" FT MUTAGEN 1588 FT /note="S->E: Decreases interaction with AHCYL1; when FT associated with A-1755." FT /evidence="ECO:0000269|PubMed:23542070" FT MUTAGEN 1755 FT /note="S->A: Increases interaction with AHCYL1; when FT associated with A-1588." FT /evidence="ECO:0000269|PubMed:23542070" FT MUTAGEN 1755 FT /note="S->E: Decreases interaction with AHCYL1; when FT associated with A-1588." FT /evidence="ECO:0000269|PubMed:23542070" FT MUTAGEN 2215 FT /note="C->A: Strongly reduced palmitoylation; when FT associated with A-56 and A-849." FT /evidence="ECO:0000269|PubMed:25368151" FT MUTAGEN 2463..2464 FT /note="KD->AA: Does not affect inositol 1,4,5- FT trisphosphate-sensitive calcium-release channel activity. FT Does not affect ERLIN2 binding." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2463..2464 FT /note="Missing: Loss of interaction with the complex FT ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not FT affect homotetramerization. Loss of inositol 1,4,5- FT trisphosphate-sensitive calcium-release channel activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2464..2465 FT /note="DD->NN: Loss of inositol 1,4,5-trisphosphate- FT sensitive calcium-release channel activity. Loss of ERLIN2 FT binding." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2465..2467 FT /note="DFI->AAA: Loss of inositol 1,4,5-trisphosphate- FT sensitive calcium-release channel activity. Loss of ERLIN2 FT binding." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2465..2467 FT /note="Missing: Loss of interaction with the complex FT ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not FT affect homotetramerization. Loss of inositol 1,4,5- FT trisphosphate-sensitive calcium-release channel activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2465 FT /note="D->N: Loss of the vast majority of inositol 1,4,5- FT trisphosphate-sensitive calcium-release channel activity. FT Loss of ERLIN2 binding." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2468..2470 FT /note="Missing: Loss of interaction with the complex FT ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not FT affect homotetramerization. Loss of inositol 1,4,5- FT trisphosphate-sensitive calcium-release channel activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2471..2472 FT /note="DR->AA: Loss of binding to the ERLIN1:ERLIN2:RNF170 FT complex. Does not affect inositol 1,4,5-trisphosphate- FT sensitive calcium-release channel activity. Does not affect FT homotetramerization." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2471..2472 FT /note="DR->GG: Loss of binding to the ERLIN1:ERLIN2:RNF170 FT complex. Does not affect inositol 1,4,5-trisphosphate- FT sensitive calcium-release channel activity. Loss of FT polyubiquitination." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2471..2472 FT /note="DR->NQ: Does not affect binding to the FT ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol FT 1,4,5-trisphosphate-sensitive calcium-release channel FT activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2471..2472 FT /note="Missing: Loss of interaction with the complex FT ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not FT affect homotetramerization. Does not affect inositol 1,4,5- FT trisphosphate-sensitive calcium-release channel activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2471 FT /note="D->N: Does not affect binding to the FT ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol FT 1,4,5-trisphosphate-sensitive calcium-release channel FT activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2472 FT /note="R->Q: Does not affect binding to the FT ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol FT 1,4,5-trisphosphate-sensitive calcium-release channel FT activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2496 FT /note="C->S: No effect on channel activity. Significant FT decrease of interaction with ERP44. Complete loss of FT channel inhibition by ERP44." FT /evidence="ECO:0000269|PubMed:15652484" FT MUTAGEN 2504 FT /note="C->S: No effect on channel activity. Significant FT decrease of interaction with ERP44. Complete loss of FT channel inhibition by ERP44." FT /evidence="ECO:0000269|PubMed:15652484" FT MUTAGEN 2527 FT /note="C->S: Complete loss of channel activity. Significant FT decrease of interaction with ERP44." FT /evidence="ECO:0000269|PubMed:15652484" FT MUTAGEN 2550 FT /note="D->A: Does not affect inositol 1,4,5-trisphosphate- FT sensitive calcium-release channel activity." FT /evidence="ECO:0000269|PubMed:35568199" FT MUTAGEN 2596 FT /note="R->A: Loss of inositol 1,4,5-trisphosphate-sensitive FT calcium-release channel activity." FT /evidence="ECO:0000269|PubMed:35568199" FT CONFLICT 1264 FT /note="N -> K (in Ref. 1; CAA33433)" FT /evidence="ECO:0000305" FT CONFLICT 2675 FT /note="P -> L (in Ref. 1; CAA33433)" FT /evidence="ECO:0000305" FT STRAND 14..23 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 25..30 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:1XZZ" FT HELIX 41..43 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:1XZZ" FT HELIX 53..56 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 58..61 FT /evidence="ECO:0007829|PDB:1XZZ" FT HELIX 67..74 FT /evidence="ECO:0007829|PDB:1XZZ" FT HELIX 86..109 FT /evidence="ECO:0007829|PDB:1XZZ" FT TURN 110..112 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 120..125 FT /evidence="ECO:0007829|PDB:1XZZ" FT TURN 126..129 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 130..139 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 146..154 FT /evidence="ECO:0007829|PDB:1XZZ" FT HELIX 157..159 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 161..167 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 181..189 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 193..199 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 201..205 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 207..213 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 217..223 FT /evidence="ECO:0007829|PDB:1XZZ" FT STRAND 239..244 FT /evidence="ECO:0007829|PDB:1N4K" FT TURN 245..248 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 249..255 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 257..265 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 272..274 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 278..280 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 303..307 FT /evidence="ECO:0007829|PDB:1N4K" FT TURN 308..310 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 313..318 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 353..359 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 364..366 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 368..371 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 388..392 FT /evidence="ECO:0007829|PDB:1N4K" FT TURN 393..396 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 397..406 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 409..412 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 415..423 FT /evidence="ECO:0007829|PDB:1N4K" FT STRAND 430..434 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 437..461 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 467..484 FT /evidence="ECO:0007829|PDB:1N4K" FT TURN 485..487 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 495..499 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 504..512 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 515..524 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 525..527 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 547..564 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 568..585 FT /evidence="ECO:0007829|PDB:1N4K" FT HELIX 589..599 FT /evidence="ECO:0007829|PDB:1N4K" SQ SEQUENCE 2749 AA; 313167 MW; FC4CF3ABB85EB82B CRC64; MSDKMSSFLH IGDICSLYAE GSTNGFISTL GLVDDRCVVQ PEAGDLNNPP 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 SPLKEDKEAF 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 STGENALEAG EDEEEVWLFW RDSNKEIRSK SVRELAQDAK EGQKEDRDIL SYYRYQLNLF ARMCLDRQYL AINEISGQLD VDLILRCMSD ENLPYDLRAS FCRLMLHMHV DRDPQEQVTP VKYARLWSEI PSEIAIDDYD SSGTSKDEIK ERFAQTMEFV EEYLRDVVCQ RFPFSDKEKN KLTFEVVNLA RNLIYFGFYN FSDLLRLTKI LLAILDCVHV TTIFPISKMT KGEENKGSNV MRSIHGVGEL MTQVVLRGGG FLPMTPMAAA PEGNVKQAEP EKEDIMVMDT KLKIIEILQF ILNVRLDYRI SCLLCIFKRE FDESNSQSSE TSSGNSSQEG PSNVPGALDF EHIEEQAEGI FGGSEENTPL DLDDHGGRTF LRVLLHLTMH DYPPLVSGAL QLLFRHFSQR QEVLQAFKQV QLLVTSQDVD NYKQIKQDLD QLRSIVEKSE LWVYKGQGPD EPMDGASGEN EHKKTEEGTS KPLKHESTSS 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 LFLKSHNIVQ KTALNWRLSA RNAARRDSVL AASRDYRNII ERLQDIVSAL EDRLRPLVQA ELSVLVDVLH RPELLFPENT DARRKCESGG FICKLIKHTK QLLEENEEKL CIKVLQTLRE MMTKDRGYGE KQISIDESEN AELPQAPEAE NSTEQELEPS PPLRQLEDHK RGEALRQILV NRYYGNIRPS GRRESLTSFG NGPLSPGGPS KPGGGGGGPG SSSTSRGEMS LAEVQCHLDK EGASNLVIDL IMNASSDRVF HESILLAIAL LEGGNTTIQH SFFCRLTEDK KSEKFFKVFY DRMKVAQQEI KATVTVNTSD LGNKKKDDEV DRDAPSRKKA KEPTTQITEE VRDQLLEASA ATRKAFTTFR READPDDHYQ SGEGTQATTD KAKDDLEMSA VITIMQPILR FLQLLCENHN RDLQNFLRCQ NNKTNYNLVC ETLQFLDCIC GSTTGGLGLL GLYINEKNVA LINQTLESLT EYCQGPCHEN QNCIATHESN GIDIITALIL NDINPLGKKR MDLVLELKNN ASKLLLAIME SRHDSENAER ILYNMRPKEL VEVIKKAYMQ GEVEFEDGEN GEDGAASPRN VGHNIYILAH QLARHNKELQ TMLKPGGQVD GDEALEFYAK HTAQIEIVRL DRTMEQIVFP VPSICEFLTK ESKLRIYYTT ERDEQGSKIN DFFLRSEDLF NEMNWQKKLR AQPVLYWCAR NMSFWSSISF NLAVLMNLLV AFFYPFKGVR GGTLEPHWSG LLWTAMLISL AIVIALPKPH GIRALIASTI LRLIFSVGLQ PTLFLLGAFN VCNKIIFLMS FVGNCGTFTR GYRAMVLDVE FLYHLLYLLI CAMGLFVHEF FYSLLLFDLV YREETLLNVI KSVTRNGRSI ILTAVLALIL VYLFSIVGYL FFKDDFILEV DRLPNETAVP ETGESLANDF LYSDVCRVET GENCTSPAPK EELLPAEETE QDKEHTCETL LMCIVTVLSH GLRSGGGVGD VLRKPSKEEP LFAARVIYDL LFFFMVIIIV LNLIFGVIID TFADLRSEKQ KKEEILKTTC FICGLERDKF DNKTVTFEEH IKEEHNMWHY LCFIVLVKVK DSTEYTGPES YVAEMIRERN LDWFPRMRAM SLVSSDSEGE QNELRNLQEK LESTMKLVTN LSGQLSELKD QMTEQRKQKQ RIGLLGHPPH MNVNPQQPA //