Q14643E7EPX7E9PDE9Q14660Q99897ITPR1_HUMANInositol 1,4,5-trisphosphate receptor type 1IP3 receptor isoform 1IP3R 1InsP3R1Type 1 inositol 1,4,5-trisphosphate receptorType 1 InsP3 receptorITPR1INSP3R1Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoHuman inositol 1,4,5-trisphosphate type-1 receptor, InsP3R1: structure, function, regulation of expression and chromosomal localization.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)The human type 1 inositol 1,4,5-trisphosphate receptor from T lymphocytes. Structure, localization, and tyrosine phosphorylation.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)PHOSPHORYLATIONSEQUENCE REVISION TO 431; 1012-1017; 1460; 1823; 2324; 2330; 2334; 2337; 2346; 2358; 2361; 2372; 2396; 2418; 2426; 2434 AND 2741Molecular cloning of a cDNA for the human inositol 1,4,5-trisphosphate receptor type 1, and the identification of a third alternatively spliced variant.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)TISSUE SPECIFICITYALTERNATIVE SPLICINGThe DNA sequence, annotation and analysis of human chromosome 3.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Induction of inositol 1,4,5 trisphosphate receptor genes by ionizing radiation.NUCLEOTIDE SEQUENCE [MRNA] OF 1548-1723 (ISOFORMS 3 AND 4)Identification of a family of calcium sensors as protein ligands of inositol trisphosphate receptor Ca(2+) release channels.INTERACTION WITH CABP1Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins.INTERACTION WITH CABP1Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44.INTERACTION WITH ERP44Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor.INTERACTION WITH AHCYL1MUTAGENESIS OF ARG-241; LYS-249; ARG-265; THR-267; ARG-269; ARG-504; ARG-506; LYS-508; ARG-511; TYR-567; ARG-568 AND LYS-569IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and thrombus formation.INTERACTION WITH IRAG1Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans.INVOLVEMENT IN SCA15A quantitative atlas of mitotic phosphorylation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598 AND SER-1764IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]An IRBIT homologue lacks binding activity to inositol 1,4,5-trisphosphate receptor due to the unique N-terminal appendage.INTERACTION WITH AHCYL1 AND AHCYL2Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-2512Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Tespa1 is a novel inositol 1,4,5-trisphosphate receptor binding protein in T and B lymphocytes.INTERACTION WITH TESPA1The Bcl-2 protein family member Bok binds to the coupling domain of inositol 1,4,5-trisphosphate receptors and protects them from proteolytic cleavage.INTERACTION WITH BOKToward a comprehensive characterization of a human cancer cell phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598 AND SER-1764IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1598IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact.INTERACTION WITH AHCYL1 AND BCL2L10Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families.VARIANT SCA15 LEU-1083Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia.VARIANTS SCA29 ASP-602 AND MET-1562ITPR1 gene p.Val1553Met mutation in Russian family with mild Spinocerebellar ataxia.VARIANT SCA29 MET-1562Recessive and dominant de novo ITPR1 mutations cause Gillespie syndrome.INVOLVEMENT IN GLSPVARIANTS GLSP LEU-2601 AND LYS-2611 DELCHARACTERIZATION OF VARIANT GLSP LYS-2611 DELFUNCTIONA restricted repertoire of de novo mutations in ITPR1 cause Gillespie syndrome with evidence for dominant-negative effect.INVOLVEMENT IN GLSPVARIANTS GLSP GLN-2109; ARG-2554 AND LYS-2611 DELSUBCELLULAR LOCATIONMutations in disordered regions can cause disease by creating dileucine motifs.MUTAGENESIS OF PRO-1059Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate (PubMed:27108797). Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 (By similarity). Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways (By similarity).Homotetramer (By similarity). Interacts with TRPC4 (By similarity). The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium-dependent manner which results in the inhibition the calcium channel activity. The strength of this interaction inversely correlates with calcium concentration. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with IRAG1 (PubMed:16990611). Interacts with CABP1 (via N-terminus) (PubMed:12032348, PubMed:14685260). Interacts with TESPA1. Interacts (when not phosphorylated) with AHCYL1 (when phosphorylated); the interaction suppresses inositol 1,4,5-trisphosphate binding to ITPR1 and is increased in the presence of BCL2L10 (PubMed:16793548, PubMed:27995898). Interacts with AHCYL2 (with lower affinity than with AHCYL1) (PubMed:19220705). Interacts with BCL2L10; the interaction is increased in the presence of AHCLY1 (PubMed:27995898). Interacts with BOK (via BH4 domain); protects ITPR1 from proteolysis by CASP3 during apoptosis (PubMed:23884412).Q14643O43865false3Q14643Q9HD36false7Endoplasmic reticulum membraneMulti-pass membrane proteinCytoplasmic vesicleSecretory vesicle membraneMulti-pass membrane proteinCytoplasmPerinuclear regionEndoplasmic reticulum and secretory granules (By similarity).Q14643-11SISIIISIIACQ14643-22SI-SIIISIIACQ14643-33SISIII-SIIQ14643-44SI-SIII-SIIQ14643-55SI-SIII-SIIACQ14643-66SISIIISIIAQ14643-77SI-SIII-SIIAQ14643-88SI-SIII-SIIAThere is a combination of three alternatively spliced domains at site SI, SIII and site SII (A and C). Experimental confirmation may be lacking for some isoforms.Widely expressed.The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.Phosphorylated on tyrosine residues.Ubiquitination at multiple lysines targets ITPR1 for proteasomal degradation. Approximately 40% of the ITPR1-associated ubiquitin is monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'-linked (By similarity).Phosphorylated by cAMP kinase (PKA). Phosphorylation prevents the ligand-induced opening of the calcium channels. Phosphorylation by PKA increases the interaction with inositol 1,4,5-trisphosphate and decreases the interaction with AHCYL1.Palmitoylated by ZDHHC6 in immune cells, leading to regulation of ITPR1 stability and function.Spinocerebellar ataxia 15
SCA15
Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA15 is an autosomal dominant cerebellar ataxia (ADCA). It is very slow progressing form with a wide range of onset, ranging from childhood to adult. Most patients remain ambulatory.The disease is caused by variants affecting the gene represented in this entry.Spinocerebellar ataxia 29
SCA29
An autosomal dominant, congenital spinocerebellar ataxia characterized by early motor delay, hypotonia and mild cognitive delay. Affected individuals develop a very slowly progressive or non-progressive gait and limb ataxia associated with cerebellar atrophy on brain imaging. Additional variable features include nystagmus, dysarthria, and tremor.The disease is caused by variants affecting the gene represented in this entry.Gillespie syndrome
GLSP
A rare disease characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, progressive cerebellar atrophy, and intellectual disability.The disease is caused by variants affecting the gene represented in this entry.Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor.Belongs to the InsP3 receptor family.Alternative splice sites (AA 1053-1054) represent a non-canonical GA-AG donor-acceptor pair, but are well-supported by all available human transcripts, and by homologous transcripts in mouse, rat and cow.Alternative splicingApoptosisCalciumCalcium channelCalcium transportCytoplasmCytoplasmic vesicleDisease variantEndoplasmic reticulumGlycoproteinIntellectual disabilityIon channelIon transportIsopeptide bondLigand-gated ion channelLipoproteinMembraneNeurodegenerationPalmitatePhosphoproteinReceptorReference proteomeRepeatSpinocerebellar ataxiaTransmembraneTransmembrane helixTransportUbl conjugation1D-myo-inositol 1,4,5-trisphosphate1D-myo-inositol 1,4,5-trisphosphate1D-myo-inositol 1,4,5-trisphosphateNDMVPLIVVMEQGRFLRQKQRQTARQRQRQKARAYARQKAPLAIAIPVDLDSQVNNLFLKSHSIVQKHCHSRGPGQPSQQPLSQVPQHCAEFLFLSAMSDKMSSFLHIGDICSLYAEGSTNGFISTLGLVDDRCVVQPETGDLNNPPKKFRDCLFKLCPMNRYSAQKQFWKAAKPGANSTTDAVLLNKLHHAADLEKKQNETENRKLLGTVIQYGNVIQLLHLKSNKYLTVNKRLPALLEKNAMRVTLDEAGNEGSWFYIQPFYKLRSIGDSVVIGDKVVLNPVNAGQPLHASSHQLVDNPGCNEVNSVNCNTSWKIVLFMKWSDNKDDILKGGDVVRLFHAEQEKFLTCDEHRKKQHVFLRTTGRQSATSATSSKALWEVEVVQHDPCRGGAGYWNSLFRFKHLATGHYLAAEVDPDFEEECLEFQPSVDPDQDASRSRLRNAQEKMVYSLVSVPEGNDISSIFELDPTTLRGGDSLVPRNSYVRLRHLCTNTWVHSTNIPIDKEEEKPVMLKIGTSPVKEDKEAFAIVPVSPAEVRDLDFANDASKVLGSIAGKLEKGTITQNERRSVTKLLEDLVYFVTGGTNSGQDVLEVVFSKPNRERQKLMREQNILKQIFKLLQAPFTDCGDGPMLRLEELGDQRHAPFRHICRLCYRVLRHSQQDYRKNQEYIAKQFGFMQKQIGYDVLAEDTITALLHNNRKLLEKHITAAEIDTFVSLVRKNREPRFLDYLSDLCVSMNKSIPVTQELICKAVLNPTNADILIETKLVLSRFEFEGVSSTGENALEAGEDEEEVWLFWRDSNKEIRSKSVRELAQDAKEGQKEDRDVLSYYRYQLNLFARMCLDRQYLAINEISGQLDVDLILRCMSDENLPYDLRASFCRLMLHMHVDRDPQEQVTPVKYARLWSEIPSEIAIDDYDSSGASKDEIKERFAQTMEFVEEYLRDVVCQRFPFSDKEKNKLTFEVVNLARNLIYFGFYNFSDLLRLTKILLAILDCVHVTTIFPISKMAKGEENKGNNDVEKLKSSNVMRSIHGVGELMTQVVLRGGGFLPMTPMAAAPEGNVKQAEPEKEDIMVMDTKLKIIEILQFILNVRLDYRISCLLCIFKREFDESNSQTSETSSGNSSQEGPSNVPGALDFEHIEEQAEGIFGGSEENTPLDLDDHGGRTFLRVLLHLTMHDYPPLVSGALQLLFRHFSQRQEVLQAFKQVQLLVTSQDVDNYKQIKQDLDQLRSIVEKSELWVYKGQGPDETMDGASGENEHKKTEEGNNKPQKHESTSSYNYRVVKEILIRLSKLCVQESASVRKSRKQQQRLLRNMGAHAVVLELLQIPYEKAEDTKMQEIMRLAHEFLQNFCAGNQQNQALLHKHINLFLNPGILEAVTMQHIFMNNFQLCSEINERVVQHFVHCIETHGRNVQYIKFLQTIVKAEGKFIKKCQDMVMAELVNSGEDVLVFYNDRASFQTLIQMMRSERDRMDENSPLMYHIHLVELLAVCTEGKNVYTEIKCNSLLPLDDIVRVVTHEDCIPEVKIAYINFLNHCYVDTEVEMKEIYTSNHMWKLFENFLVDICRACNNTSDRKHADSILEKYVTEIVMSIVTTFFSSPFSDQSTTLQTRQPVFVQLLQGVFRVYHCNWLMPSQKASVESCIRVLSDVAKSRAIAIPVDLDSQVNNLFLKSHSIVQKTAMNWRLSARNAARRDSVLAASRDYRNIIERLQDIVSALEDRLRPLVQAELSVLVDVLHRPELLFPENTDARRKCESGGFICKLIKHTKQLLEENEEKLCIKVLQTLREMMTKDRGYGEKLISIDELDNAELPPAPDSENATEELEPSPPLRQLEDHKRGEALRQVLVNRYYGNVRPSGRRESLTSFGNGPLSAGGPGKPGGGGGGSGSSSMSRGEMSLAEVQCHLDKEGASNLVIDLIMNASSDRVFHESILLAIALLEGGNTTIQHSFFCRLTEDKKSEKFFKVFYDRMKVAQQEIKATVTVNTSDLGNKKKDDEVDRDAPSRKKAKEPTTQITEEVRDQLLEASAATRKAFTTFRREADPDDHYQPGEGTQATADKAKDDLEMSAVITIMQPILRFLQLLCENHNRDLQNFLRCQNNKTNYNLVCETLQFLDCICGSTTGGLGLLGLYINEKNVALINQTLESLTEYCQGPCHENQNCIATHESNGIDIITALILNDINPLGKKRMDLVLELKNNASKLLLAIMESRHDSENAERILYNMRPKELVEVIKKAYMQGEVEFEDGENGEDGAASPRNVGHNIYILAHQLARHNKELQSMLKPGGQVDGDEALEFYAKHTAQIEIVRLDRTMEQIVFPVPSICEFLTKESKLRIYYTTERDEQGSKINDFFLRSEDLFNEMNWQKKLRAQPVLYWCARNMSFWSSISFNLAVLMNLLVAFFYPFKGVRGGTLEPHWSGLLWTAMLISLAIVIALPKPHGIRALIASTILRLIFSVGLQPTLFLLGAFNVCNKIIFLMSFVGNCGTFTRGYRAMVLDVEFLYHLLYLVICAMGLFVHEFFYSLLLFDLVYREETLLNVIKSVTRNGRSIILTAVLALILVYLFSIVGYLFFKDDFILEVDRLPNETAVPETGESLASEFLFSDVCRVESGENCSSPAPREELVPAEETEQDKEHTCETLLMCIVTVLSHGLRSGGGVGDVLRKPSKEEPLFAARVIYDLLFFFMVIIIVLNLIFGVIIDTFADLRSEKQKKEEILKTTCFICGLERDKFDNKTVTFEEHIKEEHNMWHYLCFIVLVKVKDSTEYTGPESYVAEMIKERNLDWFPRMRAMSLVSSDSEGEQNELRNLQEKLESTMKLVTNLSGQLSELKDQMTEQRKQKQRIGLLGHPPHMNVNPQQPA
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