Description: Homo sapiens inositol 1,4,5-trisphosphate receptor type 1 (ITPR1), transcript variant 2, mRNA. (from RefSeq NM_002222) RefSeq Summary (NM_002222): This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]. Gencode Transcript: ENST00000456211.8 Gencode Gene: ENSG00000150995.20 Transcript (Including UTRs) Position: hg38 chr3:4,493,452-4,847,397 Size: 353,946 Total Exon Count: 58 Strand: + Coding Region Position: hg38 chr3:4,516,492-4,846,225 Size: 329,734 Coding Exon Count: 56
ID:ITPR1_HUMAN DESCRIPTION: RecName: Full=Inositol 1,4,5-trisphosphate receptor type 1; AltName: Full=IP3 receptor isoform 1; Short=IP3R 1; Short=InsP3R1; AltName: Full=Type 1 inositol 1,4,5-trisphosphate receptor; Short=Type 1 InsP3 receptor; FUNCTION: Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate. 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). SUBUNIT: Homotetramer. Interacts with TRPC4. 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 AHCYL1 (By similarity). Interacts with MRVI1 and CABP1 (via N-terminus). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Widely expressed. DOMAIN: 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. PTM: Phosphorylated by cAMP kinase. Phosphorylation prevents the ligand-induced opening of the calcium channels (By similarity). PTM: Phosphorylated on tyrosine residues. PTM: 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). DISEASE: Defects in ITPR1 are the cause of spinocerebellar ataxia type 15 (SCA15) [MIM:606658]. 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. MISCELLANEOUS: Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium- binding protein which then inhibits the receptor. SIMILARITY: Belongs to the InsP3 receptor family. SIMILARITY: Contains 5 MIR domains. CAUTION: 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.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF08709 - Inositol 1,4,5-trisphosphate/ryanodine receptor PF00520 - Ion transport protein PF02815 - MIR domain PF08454 - RyR and IP3R Homology associated PF01365 - RIH domain
ModBase Predicted Comparative 3D Structure on Q14643
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.