MGP Database

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MGP001686

UniProt Annotations

Entry Information
Gene Nameinositol 1,4,5-trisphosphate receptor, type 1
Protein Entry
UniProt IDQ59H91
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=8; Comment=There 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.; Name=1; Synonyms=SISIIISIIAC; IsoId=Q14643-1; Sequence=Displayed; Name=2; Synonyms=SI-SIIISIIAC; IsoId=Q14643-2; Sequence=VSP_002687; Name=3; Synonyms=SISIII-SII; IsoId=Q14643-3; Sequence=VSP_002688, VSP_002689, VSP_002690; Name=4; Synonyms=SI-SIII-SII; IsoId=Q14643-4; Sequence=VSP_002687, VSP_002688, VSP_002689, VSP_002690; Name=5; Synonyms=SI-SIII-SIIAC; IsoId=Q14643-5; Sequence=VSP_002687, VSP_002688; Name=6; Synonyms=SISIIISIIA; IsoId=Q14643-6; Sequence=VSP_002690; Name=7; Synonyms=SI-SIII-SIIA; IsoId=Q14643-7; Sequence=VSP_002687, VSP_002690; Name=8; Synonyms=SI-SIII-SIIA; IsoId=Q14643-8; Sequence=VSP_002687, VSP_002688, VSP_002690;
CautionAlternative 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. {ECO:0000305}.
DiseaseSpinocerebellar ataxia 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. {ECO:0000269|PubMed:17590087, ECO:0000269|PubMed:18579805}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseSpinocerebellar ataxia 29 (SCA29) [MIM:117360]: 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. {ECO:0000269|PubMed:22986007}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe 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.
FunctionIntracellular 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). {ECO:0000250}.
MiscellaneousCalcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium- binding protein which then inhibits the receptor.
PtmPhosphorylated by cAMP kinase. Phosphorylation prevents the ligand-induced opening of the calcium channels (By similarity). {ECO:0000250}.
PtmPhosphorylated on tyrosine residues. {ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:7852357}.
PtmUbiquitination 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). {ECO:0000250}.
SimilarityBelongs to the InsP3 receptor family. {ECO:0000305}.
SimilarityContains 5 MIR domains. {ECO:0000255|PROSITE- ProRule:PRU00131}.
Subcellular LocationEndoplasmic reticulum membrane; Multi-pass membrane protein.
SubunitHomotetramer. 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). Interacts with TESPA1. {ECO:0000250, ECO:0000269|PubMed:12032348, ECO:0000269|PubMed:14685260, ECO:0000269|PubMed:15652484, ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:23650607}.
Tissue SpecificityWidely expressed.
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