ITPR3
entrez
3710
canonical
uniprot
Q14573
canonical
ensembl
ENSG00000096433
resolver
ensp
ENSP00000363435
resolver
ensp
ENSP00000475177
resolver
ensp
ENSP00000742240
resolver
enst
ENST00000374316
resolver
enst
ENST00000605930
resolver
genesymbol
ITPR3
resolver
hgnc
HGNC:6182
resolver
uniprot
A6H8K3
resolver
uniprot
Q14649
resolver
uniprot
Q59ES2
resolver
uniprot
Q5TAQ2
resolver
uniprot_entry
A6H8K3_HUMAN
resolver
uniprot_entry
ITPR3_HUMAN
resolver
uniprot_entry
Q59ES2_HUMAN
resolver
uniprot_sec
Q14649
resolver
uniprot_sec
Q5TAQ2
resolver
activity_regulation
ACTIVITY REGULATION: Inositol 1,4,5-trisphosphate-gated calcium channel is regulated by cytosolic calcium in a biphasic manner (PubMed:30013099, PubMed:35301323, PubMed:37898605). At low concentrations, cytosolic calcium binds at a high-affinity juxtamembrane domain (JD) calcium binding site, allowing ITPR3 to activate by escaping a low-energy resting state through an ensemble of preactivated states (PubMed:30013099, PubMed:35301323, PubMed:37898605). At high cytosolic calcium concentrations, ITPR3 preferentially enters an inhibited state stabilized by calcium binding at a second, low-affinity cytoplasmic domain (CD) calcium binding site (PubMed:30013099, PubMed:35301323, PubMed:37898605). {ECO:0000269|PubMed:30013099, ECO:0000269|PubMed:35301323, ECO:0000269|PubMed:37898605}.
uniprot
proteins
amino_acid_sequence
MSEMSSFLHIGDIVSLYAEGSVNGFISTLGLVDDRCVVEPAAGDLDNPPKKFRDCLFKVCPMNRYSAQKQYWKAKQTKQDKEKIADVVLLQKLQHAAQMEQKQNDTENKKVHGDVVKYGSVIQLLHMKSNKYLTVNKRLPALLEKNAMRVTLDATGNEGSWLFIQPFWKLRSNGDNVVVGDKVILNPVNAGQPLHASNYELSDNAGCKEVNSVNCNTSWKINLFMQFRDHLEEVLKGGDVVRLFHAEQEKFLTCDEYKGKLQVFLRTTLRQSATSATSSNALWEVEVVHHDPCRGGAGHWNGLYRFKHLATGNYLAAEENPSYKGDASDPKAAGMGAQGRTGRRNAGEKIKYCLVAVPHGNDIASLFELDPTTLQKTDSFVPRNSYVRLRHLCTNTWIQSTNVPIDIEEERPIRLMLGTCPTKEDKEAFAIVSVPVSEIRDLDFANDASSMLASAVEKLNEGFISQNDRRFVIQLLEDLVFFVSDVPNNGQNVLDIMVTKPNRERQKLMREQNILKQVFGILKAPFREKGGEGPLVRLEELSDQKNAPYQHMFRLCYRVLRHSQEDYRKNQEHIAKQFGMMQSQIGYDILAEDTITALLHNNRKLLEKHITKTEVETFVSLVRKNREPRFLDYLSDLCVSNHIAIPVTQELICKCVLDPKNSDILIRTELRPVKEMAQSHEYLSIEYSEEEVWLTWTDKNNEHHEKSVRQLAQEARAGNAHDENVLSYYRYQLKLFARMCLDRQYLAIDEISQQLGVDLIFLCMADEMLPFDLRASFCHLMLHVHVDRDPQELVTPVKFARLWTEIPTAITIKDYDSNLNASRDDKKNKFANTMEFVEDYLNNVVSEAVPFANEEKNKLTFEVVSLAHNLIYFGFYSFSELLRLTRTLLGIIDCVQGPPAMLQAYEDPGGKNVRRSIQGVGHMMSTMVLSRKQSVFSAPSLSAGASAAEPLDRSKFEENEDIVVMETKLKILEILQFILNVRLDYRISYLLSVFKKEFVEVFPMQDSGADGTAPAFDSTTANMNLDRIGEQAEAMFGVGKTSSMLEVDDEGGRMFLRVLIHLTMHDYAPLVSGALQLLFKHFSQRQEAMHTFKQVQLLISAQDVENYKVIKSELDRLRTMVEKSELWVDKKGSGKGEEVEAGAAKDKKERPTDEEGFLHPPGEKSSENYQIVKGILERLNKMCGVGEQMRKKQQRLLKNMDAHKVMLDLLQIPYDKGDAKMMEILRYTHQFLQKFCAGNPGNQALLHKHLHLFLTPGLLEAETMQHIFLNNYQLCSEISEPVLQHFVHLLATHGRHVQYLDFLHTVIKAEGKYVKKCQDMIMTELTNAGDDVVVFYNDKASLAHLLDMMKAARDGVEDHSPLMYHISLVDLLAACAEGKNVYTEIKCTSLLPLEDVVSVVTHEDCITEVKMAYVNFVNHCYVDTEVEMKEIYTSNHIWTLFENFTLDMARVCSKREKRVADPTLEKYVLSVVLDTINAFFSSPFSENSTSLQTHQTIVVQLLQSTTRLLECPWLQQQHKGSVEACIRTLAMVAKGRAILLPMDLDAHISSMLSSGASCAAAAQRNASSYKATTRAFPRVTPTANQWDYKNIIEKLQDIITALEERLKPLVQAELSVLVDVLHWPELLFLEGSEAYQRCESGGFLSKLIQHTKDLMESEEKLCIKVLRTLQQMLLKKTKYGDRGNQLRKMLLQNYLQNRKSTSRGDLPDPIGTGLDPDWSAIAATQCRLDKEGATKLVCDLITSTKNEKIFQESIGLAIHLLDGGNTEIQKSFHNLMMSDKKSERFFKVLHDRMKRAQQETKSTVAVNMNDLGSQPHEDREPVDPTTKGRVASFSIPGSSSRYSLGPSLRRGHEVSERVQSSEMGTSVLIMQPILRFLQLLCENHNRDLQNFLRCQNNKTNYNLVCETLQFLDIMCGSTTGGLGLLGLYINEDNVGLVIQTLETLTEYCQGPCHENQTCIVTHESNGIDIITALILNDISPLCKYRMDLVLQLKDNASKLLLALMESRHDSENAERILISLRPQELVDVIKKAYLQEEERENSEVSPREVGHNIYILALQLSRHNKQLQHLLKPVKRIQEEEAEGISSMLSLNNKQLSQMLKSSAPAQEEEEDPLAYYENHTSQIEIVRQDRSMEQIVFPVPGICQFLTEETKHRLFTTTEQDEQGSKVSDFFDQSSFLHNEMEWQRKLRSMPLIYWFSRRMTLWGSISFNLAVFINIIIAFFYPYMEGASTGVLDSPLISLLFWILICFSIAALFTKRYSIRPLIVALILRSIYYLGIGPTLNILGALNLTNKIVFVVSFVGNRGTFIRGYKAMVMDMEFLYHVGYILTSVLGLFAHELFYSILLFDLIYREETLFNVIKSVTRNGRSILLTALLALILVYLFSIVGFLFLKDDFILEVDRLPNNHSTASPLGMPHGAAAFVDTCSGDKMDCVSGLSVPEVLEEDRELDSTERACDTLLMCIVTVMNHGLRNGGGVGDILRKPSKDESLFPARVVYDLLFFFIVIIIVLNLIFGVIIDTFADLRSEKQKKEEILKTTCFICGLERDKFDNKTVSFEEHIKLEHNMWNYLYFIVLVRVKNKTDYTGPESYVAQMIKNKNLDWFPRMRAMSLVSNEGEGEQNEIRILQDKLNSTMKLVSHLTAQLNELKEQMTEQRKRRQRLGFVDVQNCISR
uniprot
proteins
disease_involvement
DISEASE: Charcot-Marie-Tooth disease, demyelinating, type 1J (CMT1J) [MIM:620111]: An autosomal dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. {ECO:0000269|PubMed:24627108, ECO:0000269|PubMed:32949214}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy (IMD133) [MIM:621254]: An autosomal dominant multisystem disorder primarily characterized by combined immunodeficiency or common variable immunodeficiency, and incompletely penetrant ectodermal dysplasia. Additional variable features include motor and speech developmental delay, poor growth, and demyelinating or axonal peripheral neuropathy. {ECO:0000269|PubMed:36302985, ECO:0000269|PubMed:39270020, ECO:0000269|PubMed:39560673}. 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 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasis (PubMed:32949214, PubMed:37898605, PubMed:8081734, PubMed:8288584, PubMed:39560673). 1D-myo-inositol 1,4,5-trisphosphate binds to the ligand-free channel without altering its global conformation, yielding the low-energy resting state, then progresses through resting-to preactivated transitions to the higher energy preactivated state, which increases affinity for calcium, promoting binding of the low basal cytosolic calcium at the juxtamembrane domain (JD) site, favoring the transition through the ensemble of high-energy intermediate states along the trajectory to the fully-open activated state (PubMed:30013099, PubMed:35301323, PubMed:37898605). Upon opening, releases calcium in the cytosol where it can bind to the low-affinity cytoplasmic domain (CD) site and stabilizes the inhibited state to terminate calcium release (PubMed:30013099, PubMed:35301323, PubMed:37898605). {ECO:0000269|PubMed:30013099, ECO:0000269|PubMed:32949214, ECO:0000269|PubMed:35301323, ECO:0000269|PubMed:37898605, ECO:0000269|PubMed:39560673, ECO:0000269|PubMed:8081734, ECO:0000269|PubMed:8288584}.
uniprot
proteins
mass_dalton
304106
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by AKT1 on serine and/or threonine residues (By similarity). {ECO:0000250|UniProtKB:P70227}.
uniprot
proteins
protein_family
InsP3 receptor family
uniprot
proteins
pubmed
12032348
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18826956
uniprot
proteins
pubmed
19553469
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23936024
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24627108
uniprot
proteins
pubmed
25996873
uniprot
proteins
pubmed
27995898
uniprot
proteins
pubmed
30013099
uniprot
proteins
pubmed
32949214
uniprot
proteins
pubmed
35301323
uniprot
proteins
pubmed
36302985
uniprot
proteins
pubmed
36471115
uniprot
proteins
pubmed
37898605
uniprot
proteins
pubmed
39270020
uniprot
proteins
pubmed
39560673
uniprot
proteins
pubmed
8081734
uniprot
proteins
pubmed
8288584
uniprot
proteins
sequence_length
2671
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:39270020, ECO:0000269|PubMed:39560673}; Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250|UniProtKB:Q8WN95}; Multi-pass membrane protein {ECO:0000255}. Note=Also localizes at mitochondria-associated membranes (MAMs). {ECO:0000269|PubMed:39270020}.
uniprot
proteins
transmembrane_region
TRANSMEM 2203..2223; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 2236..2256; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 2265..2285; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 2326..2346; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 2369..2389; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 2497..2517; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins