The ITPR1 structure has a large solenoid CY assembly built around the central helical bundle made of the C-terminal domains from four IP3R1 subunits. The solenoid scaffold includes domains responsible for binding of ligands and regulatory proteins and is connected via an allosteric nexus at the cytosolic-membrane interface to the transmembrane channel assembly. Six transmembrane helices from each subunit form the central ion-conduction pore.
Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) (PubMed:10620513, PubMed:27108797). Undergoes conformational changes upon ligand binding, suggesting structural flexibility that allows the channel to switch from a closed state, capable of interacting with its ligands such as 1,4,5-trisphosphate and calcium, to an open state, capable of transferring calcium ions across the ER membrane (By similarity). Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CAMK2 complex (By similarity). Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 (By similarity). Part of a complex composed of HSPA9, ITPR1 and VDAC1 that regulates mitochondrial calcium-dependent apoptosis by facilitating calcium transport from the ER lumen to the mitochondria intermembrane space thus providing calcium for the downstream calcium channel MCU that directly releases it into mitochondria matrix (By similarity). Regulates fertilization and egg activation by tuning the frequency and amplitude of calcium oscillations (By similarity).
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.
None
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.
None
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Polyubiquitinated (By similarity). Polyubiquitination targets ITPR1 for proteasomal degradation (By similarity). 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) enhances calcium release (By similarity). Phosphorylation by PKA increases the interaction with inositol 1,4,5-trisphosphate and decreases the interaction with AHCYL1 (By similarity).
Phosphorylated on tyrosine residues.
Palmitoylated by ZDHHC6 in immune cells, leading to regulation of ITPR1 stability and function.
Belongs to the InsP3 receptor family.
Widely expressed.
INSP3R1, ITPR1, IP3 receptor isoform 1, IP3R 1, InsP3R1, Type 1 InsP3 receptor
Proteins
Neuroscience
313929Da
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