ID ITPR1_MOUSE Reviewed; 2749 AA. AC P11881; P20943; Q99LG5; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 20-MAR-2007, entry version 89. DE Inositol 1,4,5-trisphosphate receptor type 1 (Type 1 inositol 1,4,5- DE trisphosphate receptor) (Type 1 InsP3 receptor) (IP3 receptor isoform DE 1) (InsP3R1) (Inositol 1,4,5-trisphosphate-binding protein P400) DE (Purkinje cell protein 1) (Protein PCD-6). GN Name=Itpr1; Synonyms=Insp3r, Pcd6, Pcp1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR RP LOCATION. RC TISSUE=Purkinje cell; RX MEDLINE=90044039; PubMed=2554142; DOI=10.1038/342032a0; RA Furuichi T., Yoshikawa S., Miyawaki A., Wada K., Maeda N., RA 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 MEDLINE=89345101; 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 [GENOMIC DNA] OF 318-332 AND 1692-1731, AND RP ALTERNATIVE SPLICING. RC STRAIN=ICR; RX MEDLINE=91296797; PubMed=1648733; 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 [4] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2250-2749. RC STRAIN=C57BL/6J; TISSUE=Cerebellum; RX MEDLINE=89068131; PubMed=3199205; RA Nordquist D.T., Kozak C.A., Orr H.T.; RT "cDNA cloning and characterization of three genes uniquely expressed RT in cerebellum by Purkinje neurons."; RL J. Neurosci. 8:4780-4789(1988). RN [6] RP INTERACTION WITH AHCYL1. RX MEDLINE=22526701; 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 [7] RP INTERACTION WITH TXNDC4, AND MUTAGENESIS OF CYS-2496; CYS-2504 AND RP CYS-2527. RX PubMed=15652484; DOI=10.1016/j.cell.2004.11.048; RA Higo T., Hattori M., Nakamura T., Natsume T., Michikawa T., RA 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 [8] 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 [9] 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 CC the endoplasmic reticulum following stimulation by inositol 1,4,5- CC trisphosphate. CC -!- SUBUNIT: Homotetramer. Interacts with TRPC4. The PPXXF motif binds CC HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and CC SHANK3 (By similarity). Interacts with TXNDC4 in a pH-, redox CC 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. CC Interacts with AHCYL1. CC -!- INTERACTION: CC Q9D1Q6:Txndc4; NbExp=2; IntAct=EBI-541478, EBI-541567; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum; endoplasmic reticulum CC membrane; multi-pass membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Comment=There is a combination of two alternatively spliced CC domains at site SI and site SII (A, B and C). Experimental CC confirmation may 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. Phosphorylation prevents the CC ligand-induced opening of the calcium channels. CC -!- PTM: Phosphorylated on tyrosine residues (By similarity). CC -!- MISCELLANEOUS: Calcium appears to inhibit ligand binding to the CC receptor, most probably by interacting with a distinct calcium- CC binding protein which then inhibits the receptor. CC -!- SIMILARITY: Belongs to the InsP3 receptor family. CC -!- SIMILARITY: Contains 5 MIR domains. 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; 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 PIR; S04844; ACMSIT. DR UniGene; Mm.227912; -. DR PDB; 1XZZ; X-ray; A=2-223. DR IntAct; P11881; -. DR Ensembl; ENSMUSG00000030102; Mus musculus. DR KEGG; mmu:16438; -. DR MGI; MGI:96623; Itpr1. DR LinkHub; P11881; -. DR ArrayExpress; P11881; -. DR GermOnline; ENSMUSG00000030102; Mus musculus. DR RZPD-ProtExp; IOM18653; -. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0008095; F:inositol-1,4,5-triphosphate receptor activity; TAS:MGI. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB. DR InterPro; IPR000699; Ca-rel_channel. DR InterPro; IPR000493; InsP3_rcpt_bd. DR InterPro; IPR005821; Ion_trans. DR InterPro; IPR003608; MIR. DR InterPro; IPR013662; RIH_assoc. 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 PROSITE; PS50919; MIR; 5. KW 3D-structure; Alternative splicing; Calcium; Calcium channel; KW Calcium transport; Endoplasmic reticulum; Ion transport; KW Ionic channel; Membrane; Phosphorylation; Receptor; Repeat; KW Transmembrane; Transport. FT CHAIN 1 2749 Inositol 1,4,5-trisphosphate receptor FT type 1. FT /FTId=PRO_0000153921. FT TOPO_DOM 1 2273 Cytoplasmic (Potential). FT TRANSMEM 2274 2294 Potential. FT TOPO_DOM 2295 2305 Lumenal (Potential). FT TRANSMEM 2306 2326 Potential. FT TOPO_DOM 2327 2352 Cytoplasmic (Potential). FT TRANSMEM 2353 2373 Potential. FT TOPO_DOM 2374 2396 Lumenal (Potential). FT TRANSMEM 2397 2417 Potential. FT TOPO_DOM 2418 2439 Cytoplasmic (Potential). FT TRANSMEM 2440 2460 Potential. FT TOPO_DOM 2461 2569 Lumenal (Potential). FT TRANSMEM 2570 2590 Potential. FT TOPO_DOM 2591 2749 Cytoplasmic (Potential). FT DOMAIN 112 166 MIR 1. FT DOMAIN 173 223 MIR 2. FT DOMAIN 231 287 MIR 3. FT DOMAIN 294 373 MIR 4. FT DOMAIN 379 435 MIR 5. FT REGION 2463 2528 Interaction with TXNDC4. FT MOD_RES 482 482 Phosphotyrosine (Potential). FT MOD_RES 1588 1588 Phosphoserine (By similarity). FT MOD_RES 1755 1755 Phosphoserine (by PKA) (Potential). FT MOD_RES 2655 2655 Phosphotyrosine (Potential). FT VAR_SEQ 318 332 Missing (in isoform 2, isoform 4, isoform FT 6 and isoform 8). FT /FTId=VSP_002691. FT VAR_SEQ 1692 1714 Missing (in isoform 7 and isoform 8). FT /FTId=VSP_002692. FT VAR_SEQ 1715 1715 Missing (in isoform 3, isoform 4, isoform FT 5, isoform 6, isoform 7 and isoform 8). FT /FTId=VSP_002693. FT VAR_SEQ 1716 1731 Missing (in isoform 5, isoform 6, isoform FT 7 and isoform 8). FT /FTId=VSP_002694. FT MUTAGEN 2496 2496 C->S: No effect on channel activity. FT Significant decrease of interaction with FT TXNDC4. Complete loss of channel FT inhibition by TXNDC4. FT MUTAGEN 2504 2504 C->S: No effect on channel activity. FT Significant decrease of interaction with FT TXNDC4. Complete loss of channel FT inhibition by TXNDC4. FT MUTAGEN 2527 2527 C->S: Complete loss of channel activity. FT Significant decrease of interaction with FT TXNDC4. FT CONFLICT 2675 2675 L -> P (in Ref. 4 and 5). FT STRAND 14 23 FT STRAND 25 30 FT STRAND 36 39 FT HELIX 41 43 FT STRAND 46 48 FT HELIX 53 56 FT STRAND 58 61 FT HELIX 67 74 FT HELIX 86 109 FT TURN 110 112 FT STRAND 120 125 FT TURN 126 129 FT STRAND 130 139 FT STRAND 141 143 FT STRAND 146 154 FT HELIX 157 159 FT STRAND 161 167 FT STRAND 181 189 FT STRAND 193 199 FT STRAND 201 205 FT STRAND 207 213 FT STRAND 239 244 FT TURN 245 248 FT STRAND 249 255 FT STRAND 257 265 FT STRAND 269 271 FT HELIX 272 274 FT HELIX 278 280 FT STRAND 282 286 FT STRAND 303 307 FT TURN 308 310 FT STRAND 313 318 FT STRAND 353 359 FT HELIX 364 366 FT STRAND 368 371 FT STRAND 388 392 FT TURN 393 396 FT STRAND 397 406 FT STRAND 409 412 FT STRAND 415 423 FT STRAND 430 434 FT HELIX 437 461 FT HELIX 467 484 FT TURN 485 487 FT HELIX 495 499 FT HELIX 504 512 FT HELIX 515 524 FT HELIX 525 527 FT HELIX 547 564 FT HELIX 568 585 FT HELIX 589 599 SQ SEQUENCE 2749 AA; 313197 MW; 47E5F24BCD5F4153 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 LFLKPGILEA 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 LDWFLRMRAM SLVSSDSEGE QNELRNLQEK LESTMKLVTN LSGQLSELKD QMTEQRKQKQ RIGLLGHPPH MNVNPQQPA //