ITPR1

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]

Inositol 1,4,5-Trisphosphate Receptor Type 1

Intracellular 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).

Calcium ion transport1 PublicationNAS:UniProtKB
Cell morphogenesisIEA:Ensembl
Endoplasmic reticulum calcium ion homeostasisIEA:Ensembl
Epithelial fluid transportIEA:Ensembl
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressISS:UniProtKB
Negative regulation of calcium-mediated signalingManual Assertion Based On ExperimentIDA:GO_Central
Post-embryonic developmentIEA:Ensembl
Regulation of autophagyManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Release of sequestered calcium ion into cytosolISS:UniProtKB
Response to hypoxiaManual Assertion Based On ExperimentIDA:BHF-UCL
Signal transduction1 PublicationNAS:UniProtKB
Voluntary musculoskeletal movementIEA:Ensembl

Endoplasmic reticulum membrane; Cytoplasmic vesicle, secretory vesicle membrane; Cytoplasm, perinuclear region. Endoplasmic reticulum and secretory granules (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.
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.
Gillespie syndrome (GLSP):
A rare disease characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, progressive cerebellar atrophy, and mental retardation.

Cytoplasmic: 1-2282
Helical: 2283-2303
Lumenal: 2304-2314
Helical: 2315-2335
Cytoplasmic: 2336-2361
Helical: 2362-2382
Lumenal: 2383-2405
Helical: 2406-2426
Cytoplasmic: 2427-2448
Helical: 2449-2469
Lumenal: 2470-2577
Helical: 2578-2598
Cytoplasmic: 2599-2758

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.