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 27-MAR-2024, entry version 242. 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=Inositol 1,4,5-trisphosphate-binding protein P400; DE AltName: Full=Protein PCD-6; DE AltName: Full=Purkinje cell protein 1; DE AltName: Full=Type 1 inositol 1,4,5-trisphosphate receptor; DE Short=Type 1 InsP3 receptor; GN Name=Itpr1; Synonyms=Insp3r, Pcd6, 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), FUNCTION, AND SUBCELLULAR LOCATION. 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 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 [9] 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 [10] 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 [11] RP INTERACTION WITH IRAG1, AND SUBCELLULAR LOCATION. 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 [12] 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 [13] 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 [14] 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 [15] 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 [16] RP FUNCTION, AND MUTAGENESIS OF TYR-167; LYS-168 AND 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 [17] 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 [18] 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 [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 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 [21] 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 [22] 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 [23] 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). CC -!- FUNCTION: Intracellular channel that mediates calcium release from the CC endoplasmic reticulum following stimulation by inositol 1,4,5- CC trisphosphate. Involved in the regulation of epithelial secretion of CC electrolytes and fluid through the interaction with AHCYL1 CC (PubMed:23542070). Plays a role in ER stress-induced apoptosis. CC Cytoplasmic calcium released from the ER triggers apoptosis by the CC activation of CaM kinase II, eventually leading to the activation of CC downstream apoptosis pathways. {ECO:0000269|PubMed:19752026, CC ECO:0000269|PubMed:20813840, ECO:0000269|PubMed:23542070, CC ECO:0000269|PubMed:2554142}. CC -!- SUBUNIT: Homotetramer. Interacts with TRPC4. The PPXXF motif binds CC HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and CC SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium- CC dependent manner which results in the inhibition the calcium channel CC activity. The strength of this interaction inversely correlates with CC calcium concentration. Part of cGMP kinase signaling complex at least CC composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, CC PRKG1 and ITPR1. Interacts with IRAG1 (PubMed:16990611). Interacts with CC CABP1 (via N-terminus) (By similarity). Interacts with TESPA1. 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:23542070). CC Interacts with AHCYL2 (with lower affinity than with AHCYL1) (By CC similarity). Interacts with BCL2L10; the interaction is increased in CC the presence of AHCLY1 (By similarity). Interacts with BOK (via BH4 CC domain); protects ITPR1 from proteolysis by CASP3 during apoptosis CC (PubMed:23884412). {ECO:0000250|UniProtKB:P29994, CC ECO:0000250|UniProtKB:Q14643, ECO:0000250|UniProtKB:Q9TU34, CC ECO:0000269|PubMed:12442173, 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 -!- 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:0000305|PubMed:25368151}; 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:0000250|UniProtKB:Q14643}. Note=Endoplasmic reticulum and CC secretory granules. {ECO:0000250|UniProtKB:Q9TU34, CC ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:24374158}. 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 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 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:0000305|PubMed:23542070}. CC -!- PTM: Phosphorylated on tyrosine residues. CC {ECO:0000250|UniProtKB:Q14643}. 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: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of CC ITPR1 stability and function (PubMed:25368151). CC {ECO:0000269|PubMed:25368151}. 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 -!- 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; 42. 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 EPD; P11881; -. DR jPOST; P11881; -. DR MaxQB; 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; 520 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 Genevisible; P11881; MM. 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:MGI. 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; ISO:MGI. DR GO; GO:0031094; C:platelet dense tubular network; ISO:MGI. 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:0019855; F:calcium channel inhibitor activity; ISO:MGI. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0015278; F:calcium-release channel activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. 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; IDA:SynGO. DR GO; GO:0005220; F:inositol 1,4,5-trisphosphate-sensitive calcium-release 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: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: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; ISO:MGI. 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:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL. 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; Calcium; Calcium channel; KW Calcium transport; Cytoplasm; Cytoplasmic vesicle; KW Direct protein sequencing; Endoplasmic reticulum; Ion channel; KW Ion transport; Isopeptide bond; Ligand-gated ion channel; Lipoprotein; KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat; KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation. FT CHAIN 1..2749 FT /note="Inositol 1,4,5-trisphosphate receptor type 1" FT /id="PRO_0000153921" FT TOPO_DOM 1..2273 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2274..2294 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2295..2305 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2306..2326 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2327..2352 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2353..2373 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2374..2396 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2397..2417 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2418..2439 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2440..2460 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2461..2569 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2570..2590 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2591..2749 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 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..269 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT BINDING 508..511 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT BINDING 567..569 FT /ligand="1D-myo-inositol 1,4,5-trisphosphate" FT /ligand_id="ChEBI:CHEBI:203600" FT MOD_RES 482 FT /note="Phosphotyrosine" FT /evidence="ECO:0000255" 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:Q14643, ECO:0000255" FT MOD_RES 2655 FT /note="Phosphotyrosine" FT /evidence="ECO:0000255" 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 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 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 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 //