ITPR3_RAT
ID ITPR3_RAT Reviewed; 2670 AA.
AC Q63269;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Inositol 1,4,5-trisphosphate receptor type 3;
DE AltName: Full=IP3 receptor isoform 3;
DE Short=IP3R 3;
DE Short=InsP3R3;
DE AltName: Full=Type 3 inositol 1,4,5-trisphosphate receptor;
DE Short=Type 3 InsP3 receptor;
GN Name=Itpr3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8388391; DOI=10.1016/s0021-9258(18)82132-9;
RA Blondel O., Takeda J., Janssen H., Seino S., Bell G.I.;
RT "Sequence and functional characterization of a third inositol trisphosphate
RT receptor subtype, IP3R-3, expressed in pancreatic islets, kidney,
RT gastrointestinal tract, and other tissues.";
RL J. Biol. Chem. 268:11356-11363(1993).
RN [2]
RP INTERACTION WITH TRPC4.
RX PubMed=11163362; DOI=10.1016/s0014-5793(00)02362-0;
RA Mery L., Magnino F., Schmidt K., Krause K.-H., Dufour J.-F.;
RT "Alternative splice variants of hTrp4 differentially interact with the C-
RT terminal portion of the inositol 1,4,5-trisphosphate receptors.";
RL FEBS Lett. 487:377-383(2001).
RN [3]
RP INTERACTION WITH SIGMAR1.
RX PubMed=11149946; DOI=10.1073/pnas.98.2.491;
RA Hayashi T., Su T.-P.;
RT "Regulating ankyrin dynamics: roles of sigma-1 receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:491-496(2001).
RN [4]
RP INTERACTION WITH CABP1.
RX PubMed=12032348; DOI=10.1073/pnas.102006299;
RA Yang J., McBride S., Mak D.-O.D., Vardi N., Palczewski K., Haeseleer F.,
RA Foskett J.K.;
RT "Identification of a family of calcium sensors as protein ligands of
RT inositol trisphosphate receptor Ca(2+) release channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7711-7716(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-934 AND SER-2669, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [6]
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).
CC -!- FUNCTION: Receptor for inositol 1,4,5-trisphosphate, a second messenger
CC that mediates the release of intracellular calcium.
CC -!- SUBUNIT: Homotetramer. Interacts with TRPC1 and TRPC3 (By similarity).
CC Interacts with TRPC4 (PubMed:11163362). Interacts with TRPV4 (By
CC similarity). Interacts with SIGMAR1 (PubMed:11149946). Interacts with
CC AKT1 and PML. Interacts with IRAG2 (via coiled-coil domain) (By
CC similarity). Interacts with CABP1 (PubMed:12032348). Interacts with
CC TMBIM4/LFG4 (By similarity). Interacts with CEMIP (By similarity).
CC Interacts with TESPA1 (By similarity). Interacts with TMEM203 (By
CC similarity). Interacts with BOK; regulates ITPR3 expression
CC (PubMed:23884412). Interacts with BCL2L10 (By similarity).
CC {ECO:0000250|UniProtKB:P70227, ECO:0000250|UniProtKB:Q14573,
CC ECO:0000269|PubMed:11149946, ECO:0000269|PubMed:11163362,
CC ECO:0000269|PubMed:12032348, ECO:0000269|PubMed:23884412}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- DOMAIN: The receptor contains a calcium channel in its C-terminal
CC extremity. Its large N-terminal cytoplasmic region has the ligand-
CC binding site in the N-terminus and modulatory sites in the middle
CC portion immediately upstream of the channel region.
CC -!- PTM: Phosphorylated on tyrosine residues. Phosphorylated by AKT1 on
CC serine and/or threonine residues (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the InsP3 receptor family. {ECO:0000305}.
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DR EMBL; L06096; AAA41446.1; -; mRNA.
DR PIR; A46719; A46719.
DR RefSeq; NP_037270.1; NM_013138.1.
DR AlphaFoldDB; Q63269; -.
DR SMR; Q63269; -.
DR BioGRID; 247708; 3.
DR IntAct; Q63269; 2.
DR MINT; Q63269; -.
DR STRING; 10116.ENSRNOP00000011516; -.
DR ChEMBL; CHEMBL2846; -.
DR TCDB; 1.A.3.2.5; the ryanodine-inositol 1,4,5-triphosphate receptor ca(2+) channel (rir-cac) family.
DR CarbonylDB; Q63269; -.
DR iPTMnet; Q63269; -.
DR PhosphoSitePlus; Q63269; -.
DR jPOST; Q63269; -.
DR PaxDb; Q63269; -.
DR PRIDE; Q63269; -.
DR GeneID; 25679; -.
DR KEGG; rno:25679; -.
DR UCSC; RGD:2934; rat.
DR CTD; 3710; -.
DR RGD; 2934; Itpr3.
DR eggNOG; KOG3533; Eukaryota.
DR InParanoid; Q63269; -.
DR PhylomeDB; Q63269; -.
DR Reactome; R-RNO-114508; Effects of PIP2 hydrolysis.
DR Reactome; R-RNO-139853; Elevation of cytosolic Ca2+ levels.
DR Reactome; R-RNO-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-RNO-5578775; Ion homeostasis.
DR Reactome; R-RNO-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste.
DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR PRO; PR:Q63269; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL.
DR GO; GO:0005903; C:brush border; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:RGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0043209; C:myelin sheath; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005635; C:nuclear envelope; IDA:RGD.
DR GO; GO:0005640; C:nuclear outer membrane; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0030667; C:secretory granule membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IDA:RGD.
DR GO; GO:0015085; F:calcium ion transmembrane transporter activity; TAS:RGD.
DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0043533; F:inositol 1,3,4,5 tetrakisphosphate binding; IDA:RGD.
DR GO; GO:0070679; F:inositol 1,4,5 trisphosphate binding; IDA:RGD.
DR GO; GO:0005220; F:inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; IDA:RGD.
DR GO; GO:0000822; F:inositol hexakisphosphate binding; IDA:RGD.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR GO; GO:0051592; P:response to calcium ion; ISO:RGD.
DR GO; GO:0050913; P:sensory perception of bitter taste; ISO:RGD.
DR GO; GO:0050916; P:sensory perception of sweet taste; ISO:RGD.
DR GO; GO:0050917; P:sensory perception of umami taste; ISO:RGD.
DR InterPro; IPR014821; Ins145_P3_rcpt.
DR InterPro; IPR000493; InsP3_rcpt.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR036300; MIR_dom_sf.
DR InterPro; IPR016093; MIR_motif.
DR InterPro; IPR013662; RIH_assoc-dom.
DR InterPro; IPR000699; RIH_dom.
DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf.
DR Pfam; PF08709; Ins145_P3_rec; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF02815; MIR; 1.
DR Pfam; PF08454; RIH_assoc; 1.
DR Pfam; PF01365; RYDR_ITPR; 2.
DR PRINTS; PR00779; INSP3RECEPTR.
DR SMART; SM00472; MIR; 4.
DR SUPFAM; SSF100909; SSF100909; 2.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50919; MIR; 5.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel; Calcium transport; Endoplasmic reticulum;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..2670
FT /note="Inositol 1,4,5-trisphosphate receptor type 3"
FT /id="PRO_0000153930"
FT TOPO_DOM 1..2201
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2202..2222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2223..2233
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 2234..2254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2255..2263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2264..2284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2285..2324
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 2325..2345
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2346..2367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2368..2388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2389..2495
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 2496..2516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2517..2670
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 113..173
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 174..224
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 232..288
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 295..372
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 378..434
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT REGION 321..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1132..1164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1807..1849
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1132..1161
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1827..1841
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 266..270
FT /ligand="1D-myo-inositol 1,4,5-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:203600"
FT /evidence="ECO:0000250"
FT BINDING 507..510
FT /ligand="1D-myo-inositol 1,4,5-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:203600"
FT /evidence="ECO:0000250"
FT BINDING 567..569
FT /ligand="1D-myo-inositol 1,4,5-trisphosphate"
FT /ligand_id="ChEBI:CHEBI:203600"
FT /evidence="ECO:0000250"
FT MOD_RES 916
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14573"
FT MOD_RES 934
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1813
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14573"
FT MOD_RES 1832
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14573"
FT MOD_RES 1834
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14573"
FT MOD_RES 2608
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14573"
FT MOD_RES 2669
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 2670 AA; 304286 MW; 13C787E4C2886E45 CRC64;
MNEMSSFLHI GDIVSLYAEG SVNGFISTLG LVDDRCVVEP AAGDLDNPPK KFRDCLFKVC
PMNRYSAQKQ YWKAKQTKQD KEKIADVVLL QKLQHAAQME QKQNDTENKK VHGDVVKYGS
VIQLLHMKSN KYLTVNKRLP ALLEKNAMRV TLDATGNEGS WLFIQPFWKL RSNGDNVVVG
DKVILNPVNA GQPLHASNYE LSDNVGCKEV NSVNCNTSWK INLFMQFRDH LEEVLKGGDV
VRLFHAEQEK FLTCDEYRGK LQVFLRTTLR QSATSATSSN ALWEVEVVHH DPCRGGAGHW
NGLYRFKHLA TGNYLAAEEN PSYKGDVSDP KAAGPGAQSR TGRRNAGEKI KYRLVAVPHG
NDIASLFELD PTTLQKTDSF VPRNSYVRLR HLCTNTWIQS TNAPIDVEEE RPIRLMLGTC
PTKEDKEAFA IVSVPVSEIR DLDFANDASS MLASAVEKLN EGFISQNDRR FVIQLLEDLV
FFVSDVPNNG QNVLDIMVTK PNRERQKLMR DENILKQIFG ILKAPFRDKG GEGPLVRLEE
LSDQKNAPYQ YMFRLCYRVL RHSQEDYRKN QEHIAKQFGM MQSQIGYDIL AEDTITALLH
NNRKLLEKHI TKTEVETFVS LVRKNREPRF LDYLSDLCVS NRIAIPVTQE LICKCVLDPK
NSDILIQTEL RPVKEMAQSH EYLSIEYSEE EVWLTWTDRN NEHHEKSVRQ LAQEARAGNA
HDENVLSYYR YQLKLFARMC LDRQYLAIDE ISKQLGVELL FLCMADEMLP FDLRASFCHL
MLHVHVDRDP QELVTPVKFA RLWTEIPTAI TIKDYDSNLN ASRDDKKNKF ASTMEFVEDY
LNNVVGEAVP FANDEKNILT FEVVSLAHNL IYFGFYSFSE LLRLTRTLLG IIDCIQAPAA
VLQAYEEPGG KNVRRSIQGV GHMMSTMVLS RKQSVFGASS LPTGVGVPEQ LDRSKFEDNE
HTVVMETKLK ILEILQFILN VRLDYRISYL LSVFKKEFVE VFPMQDSGAD GTAPAFDSST
ANMNLDRIGE QAEAMFGVGK TSSMLEVDDE GGRMFLRVLL HLTMHDYPPL VSGALQLLFK
HFSQRQEAMH TFKQVQLLIS AQDVENYKVI KSELDRLRTM VEKSELWVDK KGSVKGEEGE
AGASKDKKER PSDEEGFLQP HGEKSSENYQ IVKGILERLN KMCGVGEQMR KKQQRLLKNM
DAHKVMLDLL QIPYDKNDNK MMEILRYTHQ FLQKFCAGNP GNQALLHKHL QLFLTPGLLE
AETMQHIFLN NYQLCSEISE PVLQHFVHCW PTHGRHVQYL DFLHTVIKAE GKYVKKCQDM
IMTELTNAGD DVVVFYNDKA SLAHLLDMMK AARDGVEDHS PLMYHISLVD LLAACAEGKN
VYTEIKCTSL LPLEDVVSVV THEDCITEVK MAYVNFVNHC YVDTEVEMKE IYTSNHIWTL
FENFTLDMAL VCNKREKRLS DPTLEKYVLT VVLDTISAFF SSPFSENSTS LQTHQTIVVQ
LLQSTTRLLE CPWLQQQHKG SVEACVRTLA MVAKSRAILL PMDLDAHMSA LLSSGGSCSA
AAQRSAANYK TATRTFPRVI PTANQWDYKN IIEKLQDIIT ALEERLKPLV QAELSVLVDM
LHWPELLFLE GSEAYQRCES GGFLSKLIRH TKGLMESEEK LCVKVLRTLQ QMLQKKSKYG
DRGNQLRKML LQNYLQNRKS GPRGELTDPT GSGVDQDWSA IAATQCRLDK EGATKLVCDL
ITSTKNEKIF QESIGLAIRL LDGGNTEIQK SFYNLMTSDK KSERFFKVLH DRMKRAQQET
KSTVAVNMSD LGSQPREDRE PADPTTKGRV SSFSMPSSSR YSLGPGLHRG HDVSERAQNN
EMGTSVLIMR PILRFLQLLC ENHNRDLQNF LRCQNNKTNY NLVCETLQFL DIMCGSTTGG
LGLLGLYINE DNVGLVIQTL ETLTEYCQGP CHENQTCIVT HESNGIDIIT ALILNDISPL
CKYRMDLVLQ LKDNASKLLL ALMESRHDSE NAERILISLR PQELVDVIKK AYLQEEEREN
SEVSPREVGH NIYILALQLS RHNKQLQHLL KPVKRIQEEE AEGISSMLSL NNKQLSQMLK
SSAPAQEEEE DPLAYYENHT SQIEIVRQDR SMEQIVFPVP AICQFLTEET KHRLFTTTEQ
DEQGSKVSDF FDQSSFLHNE MEWQRRLRSM PLIYWFSRRM TLWGSISFNL AVFINIIIAF
FYPYVEGAST GVLGSPLISL LFWILICFSI AALFTKHYSV RPLIVALVLR SIYYLGIGPT
LNILGALNLT NKIVFVVSFV GNRGTFIRGY KAMVMDMEFL YHVGYILTSV LGLFAHELFY
SILLFDLIYR EETLFNVIKS VTRNGRSILL TALLALILVY LFSIVGFLFL KDDFILEVDR
LPGNHSRAST LGMPHGAATF MGTCSGDKMD CVSEVSVPEI LEEDEELDST ERACDTLLMC
IVTVMNHGLR NGGGVGDILR KPSKDESLFP ARVVYDLLFF FIVIIIVLNL IFGVIIDTFA
DLRSEKQKKE EILKTTCFIC GLERDKFDNK TVSFEEHIKL EHNMWNYLYF IVLVRVKNKT
DYTGPESYVA QMIKNKNLDW FPRMRAMSLV SGEGEGEQNE IRILQEKLGS TMKLVSHLTA
QLNELKEQMT EQRKRRQRLG FVDVQNCMSR
