ITPR1
entrez
3708
canonical
uniprot
Q14643
canonical
ensembl
ENSG00000150995
resolver
ensp
ENSP00000349597
resolver
ensp
ENSP00000397885
resolver
ensp
ENSP00000401671
resolver
ensp
ENSP00000497605
resolver
genesymbol
ITPR1
resolver
genesymbol_syn
INSP3R1
resolver
hgnc
HGNC:6180
resolver
uniprot
B4DER3
resolver
uniprot
B4DGH1
resolver
uniprot
E7EPX7
resolver
uniprot
E9PDE9
resolver
uniprot
Q14660
resolver
uniprot
Q59H91
resolver
uniprot
Q99897
resolver
uniprot_entry
B4DER3_HUMAN
resolver
uniprot_entry
B4DGH1_HUMAN
resolver
uniprot_entry
ITPR1_HUMAN
resolver
uniprot_entry
Q59H91_HUMAN
resolver
uniprot_sec
E7EPX7
resolver
uniprot_sec
E9PDE9
resolver
uniprot_sec
Q14660
resolver
uniprot_sec
Q99897
resolver
activity_regulation
ACTIVITY REGULATION: Inositol 1,4,5-trisphosphate-gated calcium channel activity is regulated by cytosolic calcium in a biphasic manner, with low concentrations causing activation and higher concentrations inhibiting channel opening, giving rise to calcium oscillations. ATP increases the open probability of ITPR1 by synergizing with the activating effect of these two primarily ligands, inositol 1,4,5-trisphosphate and calcium (By similarity). Inositol 1,4,5-trisphosphate-gated calcium channel activity is activated by zinc ions (By similarity). Inositol 1,4,5-trisphosphate-gated calcium channel activity is inhibited by CALM1 in a calcium-dependent manner (PubMed:10620513). {ECO:0000250|UniProtKB:P11881, ECO:0000250|UniProtKB:P29994, ECO:0000269|PubMed:10620513}.
uniprot
proteins
amino_acid_sequence
MSDKMSSFLHIGDICSLYAEGSTNGFISTLGLVDDRCVVQPETGDLNNPPKKFRDCLFKLCPMNRYSAQKQFWKAAKPGANSTTDAVLLNKLHHAADLEKKQNETENRKLLGTVIQYGNVIQLLHLKSNKYLTVNKRLPALLEKNAMRVTLDEAGNEGSWFYIQPFYKLRSIGDSVVIGDKVVLNPVNAGQPLHASSHQLVDNPGCNEVNSVNCNTSWKIVLFMKWSDNKDDILKGGDVVRLFHAEQEKFLTCDEHRKKQHVFLRTTGRQSATSATSSKALWEVEVVQHDPCRGGAGYWNSLFRFKHLATGHYLAAEVDPDFEEECLEFQPSVDPDQDASRSRLRNAQEKMVYSLVSVPEGNDISSIFELDPTTLRGGDSLVPRNSYVRLRHLCTNTWVHSTNIPIDKEEEKPVMLKIGTSPVKEDKEAFAIVPVSPAEVRDLDFANDASKVLGSIAGKLEKGTITQNERRSVTKLLEDLVYFVTGGTNSGQDVLEVVFSKPNRERQKLMREQNILKQIFKLLQAPFTDCGDGPMLRLEELGDQRHAPFRHICRLCYRVLRHSQQDYRKNQEYIAKQFGFMQKQIGYDVLAEDTITALLHNNRKLLEKHITAAEIDTFVSLVRKNREPRFLDYLSDLCVSMNKSIPVTQELICKAVLNPTNADILIETKLVLSRFEFEGVSSTGENALEAGEDEEEVWLFWRDSNKEIRSKSVRELAQDAKEGQKEDRDVLSYYRYQLNLFARMCLDRQYLAINEISGQLDVDLILRCMSDENLPYDLRASFCRLMLHMHVDRDPQEQVTPVKYARLWSEIPSEIAIDDYDSSGASKDEIKERFAQTMEFVEEYLRDVVCQRFPFSDKEKNKLTFEVVNLARNLIYFGFYNFSDLLRLTKILLAILDCVHVTTIFPISKMAKGEENKGNNDVEKLKSSNVMRSIHGVGELMTQVVLRGGGFLPMTPMAAAPEGNVKQAEPEKEDIMVMDTKLKIIEILQFILNVRLDYRISCLLCIFKREFDESNSQTSETSSGNSSQEGPSNVPGALDFEHIEEQAEGIFGGSEENTPLDLDDHGGRTFLRVLLHLTMHDYPPLVSGALQLLFRHFSQRQEVLQAFKQVQLLVTSQDVDNYKQIKQDLDQLRSIVEKSELWVYKGQGPDETMDGASGENEHKKTEEGNNKPQKHESTSSYNYRVVKEILIRLSKLCVQESASVRKSRKQQQRLLRNMGAHAVVLELLQIPYEKAEDTKMQEIMRLAHEFLQNFCAGNQQNQALLHKHINLFLNPGILEAVTMQHIFMNNFQLCSEINERVVQHFVHCIETHGRNVQYIKFLQTIVKAEGKFIKKCQDMVMAELVNSGEDVLVFYNDRASFQTLIQMMRSERDRMDENSPLMYHIHLVELLAVCTEGKNVYTEIKCNSLLPLDDIVRVVTHEDCIPEVKIAYINFLNHCYVDTEVEMKEIYTSNHMWKLFENFLVDICRACNNTSDRKHADSILEKYVTEIVMSIVTTFFSSPFSDQSTTLQTRQPVFVQLLQGVFRVYHCNWLMPSQKASVESCIRVLSDVAKSRAIAIPVDLDSQVNNLFLKSHSIVQKTAMNWRLSARNAARRDSVLAASRDYRNIIERLQDIVSALEDRLRPLVQAELSVLVDVLHRPELLFPENTDARRKCESGGFICKLIKHTKQLLEENEEKLCIKVLQTLREMMTKDRGYGEKLISIDELDNAELPPAPDSENATEELEPSPPLRQLEDHKRGEALRQVLVNRYYGNVRPSGRRESLTSFGNGPLSAGGPGKPGGGGGGSGSSSMSRGEMSLAEVQCHLDKEGASNLVIDLIMNASSDRVFHESILLAIALLEGGNTTIQHSFFCRLTEDKKSEKFFKVFYDRMKVAQQEIKATVTVNTSDLGNKKKDDEVDRDAPSRKKAKEPTTQITEEVRDQLLEASAATRKAFTTFRREADPDDHYQPGEGTQATADKAKDDLEMSAVITIMQPILRFLQLLCENHNRDLQNFLRCQNNKTNYNLVCETLQFLDCICGSTTGGLGLLGLYINEKNVALINQTLESLTEYCQGPCHENQNCIATHESNGIDIITALILNDINPLGKKRMDLVLELKNNASKLLLAIMESRHDSENAERILYNMRPKELVEVIKKAYMQGEVEFEDGENGEDGAASPRNVGHNIYILAHQLARHNKELQSMLKPGGQVDGDEALEFYAKHTAQIEIVRLDRTMEQIVFPVPSICEFLTKESKLRIYYTTERDEQGSKINDFFLRSEDLFNEMNWQKKLRAQPVLYWCARNMSFWSSISFNLAVLMNLLVAFFYPFKGVRGGTLEPHWSGLLWTAMLISLAIVIALPKPHGIRALIASTILRLIFSVGLQPTLFLLGAFNVCNKIIFLMSFVGNCGTFTRGYRAMVLDVEFLYHLLYLVICAMGLFVHEFFYSLLLFDLVYREETLLNVIKSVTRNGRSIILTAVLALILVYLFSIVGYLFFKDDFILEVDRLPNETAVPETGESLASEFLFSDVCRVESGENCSSPAPREELVPAEETEQDKEHTCETLLMCIVTVLSHGLRSGGGVGDVLRKPSKEEPLFAARVIYDLLFFFMVIIIVLNLIFGVIIDTFADLRSEKQKKEEILKTTCFICGLERDKFDNKTVTFEEHIKEEHNMWHYLCFIVLVKVKDSTEYTGPESYVAEMIKERNLDWFPRMRAMSLVSSDSEGEQNELRNLQEKLESTMKLVTNLSGQLSELKDQMTEQRKQKQRIGLLGHPPHMNVNPQQPA
uniprot
proteins
disease_involvement
DISEASE: Spinocerebellar 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 variants affecting the gene represented in this entry.; DISEASE: Spinocerebellar 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, ECO:0000269|PubMed:26770814}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Gillespie syndrome (GLSP) [MIM:206700]: A rare disease characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, progressive cerebellar atrophy, and intellectual disability. {ECO:0000269|PubMed:27108797, ECO:0000269|PubMed:27108798}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: 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). {ECO:0000250|UniProtKB:P11881, ECO:0000250|UniProtKB:P29994, ECO:0000269|PubMed:10620513, ECO:0000269|PubMed:27108797}.
uniprot
proteins
mass_dalton
313929
uniprot
proteins
mutagenesis
MUTAGEN 241; /note="R->Q: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 249; /note="K->Q: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 265; /note="R->Q: No effect on interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 267; /note="T->A: No effect on interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 269; /note="R->Q: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 504; /note="R->Q: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 506; /note="R->Q: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 508; /note="K->A: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 511; /note="R->A: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 567; /note="Y->A: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 568; /note="R->Q: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 569; /note="K->A: Abolishes interaction with AHCYL1."; /evidence="ECO:0000269|PubMed:16793548"; MUTAGEN 1059; /note="P->L: Creates a dileucine motif and recruits clathrin."; /evidence="ECO:0000269|PubMed:30197081
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:P29994}.; PTM: 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). {ECO:0000250|UniProtKB:P11881, ECO:0000250|UniProtKB:P29994}.; PTM: Phosphorylated on tyrosine residues. {ECO:0000269|PubMed:7852357}.; PTM: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of ITPR1 stability and function. {ECO:0000250|UniProtKB:P11881}.
uniprot
proteins
protein_family
InsP3 receptor family
uniprot
proteins
pubmed
10620513
uniprot
proteins
pubmed
12032348
uniprot
proteins
pubmed
14685260
uniprot
proteins
pubmed
15652484
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16793548
uniprot
proteins
pubmed
16990611
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17590087
uniprot
proteins
pubmed
18579805
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19220705
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
22986007
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23650607
uniprot
proteins
pubmed
23884412
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26770814
uniprot
proteins
pubmed
27108797
uniprot
proteins
pubmed
27108798
uniprot
proteins
pubmed
27995898
uniprot
proteins
pubmed
30197081
uniprot
proteins
pubmed
7500840
uniprot
proteins
pubmed
7852357
uniprot
proteins
pubmed
7945203
uniprot
proteins
pubmed
8648241
uniprot
proteins
sequence_length
2758
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305|PubMed:27108798, ECO:0000305|PubMed:7852357}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P29994, ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250|UniProtKB:Q9TU34}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P29994, ECO:0000255}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:27108798}. Note=Found in a complex with HSPA9 and VDAC1 at the endoplasmic reticulum-mitochondria contact sites. {ECO:0000250|UniProtKB:P29994}.
uniprot
proteins
transmembrane_region
TRANSMEM 2283..2303; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2315..2335; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2362..2382; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2406..2426; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2449..2469; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2578..2598; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255
uniprot
proteins