Itpr1
entrez
16438
canonical
uniprot
P11881
canonical
ensembl
ENSMUSG00000030102
resolver
ensp
ENSMUSP00000032192
resolver
ensp
ENSMUSP00000144880
resolver
genesymbol
Itpr1
resolver
genesymbol_syn
Insp3r
resolver
genesymbol_syn
Pcd6
resolver
genesymbol_syn
Pcp1
resolver
uniprot
P20943
resolver
uniprot
Q3UVA1
resolver
uniprot
Q8BQN0
resolver
uniprot
Q8C7X9
resolver
uniprot
Q8C8N0
resolver
uniprot
Q99LG5
resolver
uniprot_entry
ITPR1_MOUSE
resolver
uniprot_entry
Q3UVA1_MOUSE
resolver
uniprot_entry
Q8BQN0_MOUSE
resolver
uniprot_entry
Q8C7X9_MOUSE
resolver
uniprot_entry
Q8C8N0_MOUSE
resolver
uniprot_sec
P20943
resolver
uniprot_sec
Q99LG5
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 (PubMed:38099643). Inositol 1,4,5-trisphosphate-gated calcium channel activity is inhibited by CALM1 in a calcium-dependent manner (By similarity). {ECO:0000250|UniProtKB:P29994, ECO:0000250|UniProtKB:Q14643, ECO:0000269|PubMed:38099643}.
uniprot
proteins
amino_acid_sequence
MSDKMSSFLHIGDICSLYAEGSTNGFISTLGLVDDRCVVQPEAGDLNNPPKKFRDCLFKLCPMNRYSAQKQFWKAAKPGANSTTDAVLLNKLHHAADLEKKQNETENRKLLGTVIQYGNVIQLLHLKSNKYLTVNKRLPALLEKNAMRVTLDEAGNEGSWFYIQPFYKLRSIGDSVVIGDKVVLNPVNAGQPLHASSHQLVDNPGCNEVNSVNCNTSWKIVLFMKWSDNKDDILKGGDVVRLFHAEQEKFLTCDEHRKKQHVFLRTTGRQSATSATSSKALWEVEVVQHDPCRGGAGYWNSLFRFKHLATGHYLAAEVDPDFEEECLEFQPSVDPDQDASRSRLRNAQEKMVYSLVSVPEGNDISSIFELDPTTLRGGDSLVPRNSYVRLRHLCTNTWVHSTNIPIDKEEEKPVMLKIGTSPLKEDKEAFAIVPVSPAEVRDLDFANDASKVLGSIAGKLEKGTITQNERRSVTKLLEDLVYFVTGGTNSGQDVLEVVFSKPNRERQKLMREQNILKQIFKLLQAPFTDCGDGPMLRLEELGDQRHAPFRHICRLCYRVLRHSQQDYRKNQEYIAKQFGFMQKQIGYDVLAEDTITALLHNNRKLLEKHITAAEIDTFVSLVRKNREPRFLDYLSDLCVSMNKSIPVTQELICKAVLNPTNADILIETKLVLSRFEFEGVSTGENALEAGEDEEEVWLFWRDSNKEIRSKSVRELAQDAKEGQKEDRDILSYYRYQLNLFARMCLDRQYLAINEISGQLDVDLILRCMSDENLPYDLRASFCRLMLHMHVDRDPQEQVTPVKYARLWSEIPSEIAIDDYDSSGTSKDEIKERFAQTMEFVEEYLRDVVCQRFPFSDKEKNKLTFEVVNLARNLIYFGFYNFSDLLRLTKILLAILDCVHVTTIFPISKMTKGEENKGSNVMRSIHGVGELMTQVVLRGGGFLPMTPMAAAPEGNVKQAEPEKEDIMVMDTKLKIIEILQFILNVRLDYRISCLLCIFKREFDESNSQSSETSSGNSSQEGPSNVPGALDFEHIEEQAEGIFGGSEENTPLDLDDHGGRTFLRVLLHLTMHDYPPLVSGALQLLFRHFSQRQEVLQAFKQVQLLVTSQDVDNYKQIKQDLDQLRSIVEKSELWVYKGQGPDEPMDGASGENEHKKTEEGTSKPLKHESTSSYNYRVVKEILIRLSKLCVQESASVRKSRKQQQRLLRNMGAHAVVLELLQIPYEKAEDTKMQEIMRLAHEFLQNFCAGNQQNQALLHKHINLFLNPGILEAVTMQHIFMNNFQLCSEINERVVQHFVHCIETHGRNVQYIKFLQTIVKAEGKFIKKCQDMVMAELVNSGEDVLVFYNDRASFQTLIQMMRSERDRMDENSPLMYHIHLVELLAVCTEGKNVYTEIKCNSLLPLDDIVRVVTHEDCIPEVKIAYINFLNHCYVDTEVEMKEIYTSNHMWKLFENFLVDICRACNNTSDRKHADSILEKYVTEIVMSIVTTFFSSPFSDQSTTLQTRQPVFVQLLQGVFRVYHCNWLMPSQKASVESCIRVLSDVAKSRAIAIPVDLDSQVNNLFLKSHNIVQKTALNWRLSARNAARRDSVLAASRDYRNIIERLQDIVSALEDRLRPLVQAELSVLVDVLHRPELLFPENTDARRKCESGGFICKLIKHTKQLLEENEEKLCIKVLQTLREMMTKDRGYGEKQISIDESENAELPQAPEAENSTEQELEPSPPLRQLEDHKRGEALRQILVNRYYGNIRPSGRRESLTSFGNGPLSPGGPSKPGGGGGGPGSSSTSRGEMSLAEVQCHLDKEGASNLVIDLIMNASSDRVFHESILLAIALLEGGNTTIQHSFFCRLTEDKKSEKFFKVFYDRMKVAQQEIKATVTVNTSDLGNKKKDDEVDRDAPSRKKAKEPTTQITEEVRDQLLEASAATRKAFTTFRREADPDDHYQSGEGTQATTDKAKDDLEMSAVITIMQPILRFLQLLCENHNRDLQNFLRCQNNKTNYNLVCETLQFLDCICGSTTGGLGLLGLYINEKNVALINQTLESLTEYCQGPCHENQNCIATHESNGIDIITALILNDINPLGKKRMDLVLELKNNASKLLLAIMESRHDSENAERILYNMRPKELVEVIKKAYMQGEVEFEDGENGEDGAASPRNVGHNIYILAHQLARHNKELQTMLKPGGQVDGDEALEFYAKHTAQIEIVRLDRTMEQIVFPVPSICEFLTKESKLRIYYTTERDEQGSKINDFFLRSEDLFNEMNWQKKLRAQPVLYWCARNMSFWSSISFNLAVLMNLLVAFFYPFKGVRGGTLEPHWSGLLWTAMLISLAIVIALPKPHGIRALIASTILRLIFSVGLQPTLFLLGAFNVCNKIIFLMSFVGNCGTFTRGYRAMVLDVEFLYHLLYLLICAMGLFVHEFFYSLLLFDLVYREETLLNVIKSVTRNGRSIILTAVLALILVYLFSIVGYLFFKDDFILEVDRLPNETAVPETGESLANDFLYSDVCRVETGENCTSPAPKEELLPAEETEQDKEHTCETLLMCIVTVLSHGLRSGGGVGDVLRKPSKEEPLFAARVIYDLLFFFMVIIIVLNLIFGVIIDTFADLRSEKQKKEEILKTTCFICGLERDKFDNKTVTFEEHIKEEHNMWHYLCFIVLVKVKDSTEYTGPESYVAEMIRERNLDWFPRMRAMSLVSSDSEGEQNELRNLQEKLESTMKLVTNLSGQLSELKDQMTEQRKQKQRIGLLGHPPHMNVNPQQPA
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) and participates in calcium oscillations (PubMed:11955285, PubMed:12442173, PubMed:20813840, PubMed:2554142, PubMed:28416699, PubMed:35568199, PubMed:38099643). 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 inositol 1,4,5-trisphosphate and Ca(2+), 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 (PubMed:19752026). 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 (PubMed:29907098). Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 (PubMed:23542070). Regulates fertilization and egg activation by tuning the frequency and amplitude of calcium oscillations (PubMed:38099643). {ECO:0000250|UniProtKB:P29994, ECO:0000269|PubMed:11955285, ECO:0000269|PubMed:12442173, ECO:0000269|PubMed:19752026, ECO:0000269|PubMed:20813840, ECO:0000269|PubMed:23542070, ECO:0000269|PubMed:2554142, ECO:0000269|PubMed:28416699, ECO:0000269|PubMed:29907098, ECO:0000269|PubMed:35568199, ECO:0000269|PubMed:38099643}.
uniprot
proteins
mass_dalton
313167
uniprot
proteins
mutagenesis
MUTAGEN 56; /note="C->A: Strongly reduced palmitoylation; when associated with A-849 and A-2215."; /evidence="ECO:0000269|PubMed:25368151"; MUTAGEN 167; /note="Y->A: Nearly abolishes calcium flux."; /evidence="ECO:0000269|PubMed:20813840"; MUTAGEN 168; /note="K->A: Reduces calcium flux by about 50%."; /evidence="ECO:0000269|PubMed:20813840"; MUTAGEN 169; /note="L->A: Reduces calcium flux by about 50%."; /evidence="ECO:0000269|PubMed:20813840"; MUTAGEN 267; /note="T->A: Abolishes inositol 1,4,5-triphosphate binding."; /evidence="ECO:0000269|PubMed:12442173"; MUTAGEN 567; /note="Y->A,F: Abolishes inositol 1,4,5-triphosphate binding."; /evidence="ECO:0000269|PubMed:12442173"; MUTAGEN 849; /note="C->A: Strongly reduced palmitoylation; when associated with A-56 and A-2215."; /evidence="ECO:0000269|PubMed:25368151"; MUTAGEN 1588; /note="S->A: Increases interaction with AHCYL1; when associated with A-1755."; /evidence="ECO:0000269|PubMed:23542070"; MUTAGEN 1588; /note="S->E: Decreases interaction with AHCYL1; when associated with A-1755."; /evidence="ECO:0000269|PubMed:23542070"; MUTAGEN 1755; /note="S->A: Increases interaction with AHCYL1; when associated with A-1588."; /evidence="ECO:0000269|PubMed:23542070"; MUTAGEN 1755; /note="S->E: Decreases interaction with AHCYL1; when associated with A-1588."; /evidence="ECO:0000269|PubMed:23542070"; MUTAGEN 2215; /note="C->A: Strongly reduced palmitoylation; when associated with A-56 and A-849."; /evidence="ECO:0000269|PubMed:25368151"; MUTAGEN 2463..2464; /note="KD->AA: Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity. Does not affect ERLIN2 binding."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2463..2464; /note="Missing: Loss of interaction with the complex ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not affect homotetramerization. Loss of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2464..2465; /note="DD->NN: Loss of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity. Loss of ERLIN2 binding."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2465..2467; /note="DFI->AAA: Loss of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity. Loss of ERLIN2 binding."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2465..2467; /note="Missing: Loss of interaction with the complex ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not affect homotetramerization. Loss of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2465; /note="D->N: Loss of the vast majority of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity. Loss of ERLIN2 binding."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2468..2470; /note="Missing: Loss of interaction with the complex ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not affect homotetramerization. Loss of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2471..2472; /note="DR->AA: Loss of binding to the ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity. Does not affect homotetramerization."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2471..2472; /note="DR->GG: Loss of binding to the ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity. Loss of polyubiquitination."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2471..2472; /note="DR->NQ: Does not affect binding to the ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2471..2472; /note="Missing: Loss of interaction with the complex ERLIN1:ERLIN2:RNF170 after stimulation with GNRH1. Does not affect homotetramerization. Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2471; /note="D->N: Does not affect binding to the ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2472; /note="R->Q: Does not affect binding to the ERLIN1:ERLIN2:RNF170 complex. Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2496; /note="C->S: No effect on channel activity. Significant decrease of interaction with ERP44. Complete loss of channel inhibition by ERP44."; /evidence="ECO:0000269|PubMed:15652484"; MUTAGEN 2504; /note="C->S: No effect on channel activity. Significant decrease of interaction with ERP44. Complete loss of channel inhibition by ERP44."; /evidence="ECO:0000269|PubMed:15652484"; MUTAGEN 2527; /note="C->S: Complete loss of channel activity. Significant decrease of interaction with ERP44."; /evidence="ECO:0000269|PubMed:15652484"; MUTAGEN 2550; /note="D->A: Does not affect inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199"; MUTAGEN 2596; /note="R->A: Loss of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity."; /evidence="ECO:0000269|PubMed:35568199
uniprot
proteins
post_translational_modification
PTM: Polyubiquitinated (PubMed:35568199). Polyubiquitination targets ITPR1 for proteasomal degradation (PubMed:35568199). 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, ECO:0000269|PubMed:35568199}.; PTM: Phosphorylation 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 (Probable). {ECO:0000250|UniProtKB:P29994, ECO:0000305|PubMed:23542070}.; PTM: Phosphorylated on tyrosine residues. {ECO:0000250|UniProtKB:Q14643}.; PTM: Palmitoylated by ZDHHC6 in immune cells, leading to regulation of ITPR1 stability and function (PubMed:25368151). {ECO:0000269|PubMed:25368151}.
uniprot
proteins
protein_family
InsP3 receptor family
uniprot
proteins
pubmed
10620513
uniprot
proteins
pubmed
11955285
uniprot
proteins
pubmed
12442173
uniprot
proteins
pubmed
12525476
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15652484
uniprot
proteins
pubmed
15664189
uniprot
proteins
pubmed
1648733
uniprot
proteins
pubmed
16527252
uniprot
proteins
pubmed
16990611
uniprot
proteins
pubmed
17208939
uniprot
proteins
pubmed
18630941
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19752026
uniprot
proteins
pubmed
20813840
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23542070
uniprot
proteins
pubmed
23650607
uniprot
proteins
pubmed
23884412
uniprot
proteins
pubmed
24374158
uniprot
proteins
pubmed
25368151
uniprot
proteins
pubmed
2554142
uniprot
proteins
pubmed
2762133
uniprot
proteins
pubmed
28416699
uniprot
proteins
pubmed
29907098
uniprot
proteins
pubmed
3199205
uniprot
proteins
pubmed
35568199
uniprot
proteins
pubmed
38099643
uniprot
proteins
sequence_length
2749
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:28416699, ECO:0000305|PubMed:24374158, ECO:0000305|PubMed:25368151}; 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:0000250|UniProtKB:Q14643}. Note=Found in a complex with HSPA9 and VDAC1 at the endoplasmic reticulum-mitochondria contact sites. {ECO:0000250|UniProtKB:P29994, ECO:0000250|UniProtKB:Q9TU34}.
uniprot
proteins
transmembrane_region
TRANSMEM 2274..2294; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2306..2326; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2353..2373; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2397..2417; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2440..2460; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255"; TRANSMEM 2570..2590; /note="Helical"; /evidence="ECO:0000250|UniProtKB:P29994, ECO:0000255
uniprot
proteins