Itpr3 encodes the type 3 inositol 1,4,5-trisphosphate receptor (IP3R3), a 2,670-residue multi-pass membrane protein that assembles into homo- or heterotetrameric ligand-gated Ca2+ release channels in the endoplasmic reticulum membrane and the ER-continuous nuclear envelope. Binding of IP3, produced by phospholipase C downstream of Gq-coupled and tyrosine kinase receptors, to the N-terminal binding core, together with cytosolic Ca2+ (biphasic activation and inhibition) and ATP (a low-affinity, cooperative modulatory site), opens a six-transmembrane-helix pore per subunit and releases ER Ca2+ into the cytosol. Rat IP3R3 single channels have the same ~75 pS conductance as other subtypes but a lower apparent IP3 affinity; its sensitivity is increased by PKA phosphorylation and by cAMP acting independently of PKA, and decreased by PKC. IP3R3 is the predominant subtype in pancreatic beta-cells and islets, insulinoma cells, many secretory epithelia (where it concentrates at the apical pole), Schwann cells, taste receptor cells and some forebrain neuronal terminals, where its Ca2+ signals couple receptor activation to secretion and sensory transduction.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000822 inositol hexakisphosphate binding | IDA PMID:8388391 Sequence and functional characterization of a third inositol... | KEEP AS NON CORE | Summary: Recombinant rat IP3R3 binds inositol hexakisphosphate in competition binding. Reason: The abstract reports InsP6 binding by recombinant rat IP3R3; this is low-affinity competition at the IP3 site, not a physiological ligand of the channel. Kept as non-core. Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro ion-transport domain mapping to ion channel activity. Reason: Correct but general; the specific child GO:0005220 is directly supported for rat IP3R3 and already carried by the gene. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 file:rat/Itpr3/Itpr3-deep-research-manual.md Recombinant rat IP3R3 recorded in planar bilayers: 74-80 pS, open probability 30-40%, apparent IP3 affinity 0.40 microM, |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IDA PMID:10694253 Single-channel properties in endoplasmic reticulum membrane ... | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IDA PMID:15533917 Functional characterization of mammalian inositol 1,4,5-tris... | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IDA PMID:17320950 Protein kinase C decreases the apparent affinity of the inos... | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:17320950 RINm5F cells who express almost exclusively (approximately 90%) the IP3R-3, represent an interesting model to study this particular isoform. PMID:17320950 whereby activated PKC dampens IP3R-3 activity PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IDA PMID:17373911 Protein kinase A increases the binding affinity and the Ca2+... | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:17373911 binding affinity and IP(3)-induced Ca2+ release activity were enhanced in permeabilized cells that were pre-treated with forskolin or PKA. PMID:17373911 RINm5F cells express almost exclusively the IP(3)R-3 subtype. PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | ISO GO_REF:0000121 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | ISO GO_REF:0000121 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | ISS GO_REF:0000024 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | TAS PMID:11788349 Intracellular signal transduction during gastrin-induced his... | ACCEPT | Summary: IP3-gated Ca2+ release channel activity of IP3R3. Reason: Rat IP3R3 forms an IP3-gated Ca2+ channel: recombinant rat IP3R3 gives 74-80 pS IP3-activated single channels in planar bilayers (PMID:15533917) and in the native ER/outer nuclear membrane of Xenopus oocytes, where >90% of recorded channels were rat IP3R3 homotetramers (PMID:10694253). IP3-induced Ca2+ release in RINm5F cells, which express ~90% IP3R3, is tuned by PKA and PKC (PMID:17373911, PMID:17320950). This is the core activity. Supporting Evidence: PMID:11788349 gastrin-stimulated histamine release depends on IP(3)R activation and plasmalemmal calcium entry. PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005262 calcium channel activity | IEA GO_REF:0000002 | MODIFY | Summary: RIH-domain mapping to calcium channel activity. Reason: Correct but general; refine to the IP3-gated Ca2+ channel term already carried with direct rat evidence. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Ca2+ binding at regulatory sites of the IP3R. Reason: Cytosolic Ca2+ is a co-agonist that regulates IP3R3 biphasically through a high-affinity juxtamembrane site and a low-affinity cytoplasmic-domain site (UniProt, by similarity to human ITPR3 cryo-EM structures). Ca2+ binding is a regulatory property of the channel, not its core activity; kept as non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Inositol 1,4,5-trisphosphate-gated calcium channel is regulated by cytosolic calcium in a biphasic manner. file:rat/Itpr3/Itpr3-uniprot.txt ligand="Ca(2+)" |
| GO:0005509 calcium ion binding | IDA PMID:17320950 Protein kinase C decreases the apparent affinity of the inos... | KEEP AS NON CORE | Summary: Ca2+ binding attributed to IP3R3 in RINm5F cell studies of kinase regulation. Reason: Cytosolic Ca2+ is a co-agonist that regulates IP3R3 biphasically through a high-affinity juxtamembrane site and a low-affinity cytoplasmic-domain site (UniProt, by similarity to human ITPR3 cryo-EM structures). Ca2+ binding is a regulatory property of the channel, not its core activity; kept as non-core. The cached abstract does not describe the Ca2+-binding assay; deferring to the RGD curator who read the full text. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Inositol 1,4,5-trisphosphate-gated calcium channel is regulated by cytosolic calcium in a biphasic manner. file:rat/Itpr3/Itpr3-uniprot.txt ligand="Ca(2+)" |
| GO:0005509 calcium ion binding | IDA PMID:17373911 Protein kinase A increases the binding affinity and the Ca2+... | KEEP AS NON CORE | Summary: Ca2+ binding attributed to IP3R3 in RINm5F cell studies of kinase regulation. Reason: Cytosolic Ca2+ is a co-agonist that regulates IP3R3 biphasically through a high-affinity juxtamembrane site and a low-affinity cytoplasmic-domain site (UniProt, by similarity to human ITPR3 cryo-EM structures). Ca2+ binding is a regulatory property of the channel, not its core activity; kept as non-core. The cached abstract does not describe the Ca2+-binding assay; deferring to the RGD curator who read the full text. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Inositol 1,4,5-trisphosphate-gated calcium channel is regulated by cytosolic calcium in a biphasic manner. file:rat/Itpr3/Itpr3-uniprot.txt ligand="Ca(2+)" |
| GO:0005509 calcium ion binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Ca2+ binding transferred from human ITPR3. Reason: Cytosolic Ca2+ is a co-agonist that regulates IP3R3 biphasically through a high-affinity juxtamembrane site and a low-affinity cytoplasmic-domain site (UniProt, by similarity to human ITPR3 cryo-EM structures). Ca2+ binding is a regulatory property of the channel, not its core activity; kept as non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Inositol 1,4,5-trisphosphate-gated calcium channel is regulated by cytosolic calcium in a biphasic manner. file:rat/Itpr3/Itpr3-uniprot.txt ligand="Ca(2+)" |
| GO:0005515 protein binding | IPI PMID:21424589 Inositol 1, 4, 5-trisphosphate receptor interacts with the S... | REMOVE | Summary: Interaction with syntaxin 1B (P61265). Reason: Bare protein binding is uninformative and removed under the protein-binding policy. The paper maps the syntaxin 1B SNARE domain onto the IP3R1 coupling domain; the cached abstract does not establish a mechanism specific to IP3R3. Supporting Evidence: PMID:21424589 We show that IP(3)Rs interact with syntaxin 1 (Syx1) |
| GO:0005515 protein binding | IPI PMID:23884412 The Bcl-2 protein family member Bok binds to the coupling do... | REMOVE | Summary: Interaction with Bok (O35425). Reason: Bare protein binding is uninformative and removed under the protein-binding policy; moreover the paper reports Bok binds IP3R3 only weakly. Supporting Evidence: PMID:23884412 Bok binds most strongly to IP3R1 and IP3R2, and barely to IP3R3 |
| GO:0005524 ATP binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ATP binding at the modulatory site. Reason: ATP is a modulatory ligand: rat IP3R3 has a low-affinity (2 mM), highly cooperative ATP modulatory site (PMID:15533917), and UniProt annotates ATP-binding residues by similarity to human ITPR3 structures. Modulatory, non-core. Supporting Evidence: PMID:15533917 InsP3R3 has a low-affinity (2 mM) ATP modulatory site file:rat/Itpr3/Itpr3-uniprot.txt ligand="ATP" |
| GO:0005524 ATP binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ATP binding at the modulatory site. Reason: ATP is a modulatory ligand: rat IP3R3 has a low-affinity (2 mM), highly cooperative ATP modulatory site (PMID:15533917), and UniProt annotates ATP-binding residues by similarity to human ITPR3 structures. Modulatory, non-core. Supporting Evidence: PMID:15533917 InsP3R3 has a low-affinity (2 mM) ATP modulatory site file:rat/Itpr3/Itpr3-uniprot.txt ligand="ATP" |
| GO:0005634 nucleus | ISO GO_REF:0000121 | MODIFY | Summary: Nucleus transferred from mouse Itpr3. Reason: IP3R3 is a membrane protein of the ER that is continuous with the nuclear envelope; channels were recorded from the outer nuclear membrane (PMID:10694253). The informative location is the nuclear envelope (GO:0005635, already carried by IDA), not the nucleus as a whole. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96624 SUPPORTS TRANSFER Nuclear localisation is consistent with nuclear-envelope IP3R; refined. Proposed replacements: nuclear envelope Supporting Evidence: PMID:10694253 Use of conditions that were similar to those previously employed in studies of the endogenous type 1 InsP3R channel in the outer nuclear membrane has now enabled the first comparison of the permeation and gating properties of different InsP3R isoforms in the same native membrane environment. PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. |
| GO:0005635 nuclear envelope | IDA PMID:15537642 Translational mobility of the type 3 inositol 1,4,5-trisphos... | KEEP AS NON CORE | Summary: Nuclear envelope location of GFP-IP3R3. Reason: The ER-membrane IP3R3 extends into the ER-continuous nuclear envelope; the cached abstract reports free diffusion throughout a continuous ER, consistent with envelope labelling seen by the curator in the full text. Non-core extension of the ER location. Supporting Evidence: PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:15537642 We conclude that the entire ER is continuous in these cells, with the large majority of InsP3R3 channels free to diffuse throughout it |
| GO:0005640 nuclear outer membrane | IDA PMID:8388391 Sequence and functional characterization of a third inositol... | KEEP AS NON CORE | Summary: Outer nuclear membrane location of recombinant IP3R3. Reason: Recombinant rat IP3R3 localises to the ER (PMID:8388391) and functional rat IP3R3 channels were recorded by patch clamp of the outer nuclear membrane (PMID:10694253). Part of the ER-continuous membrane; non-core. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:10694253 Use of conditions that were similar to those previously employed in studies of the endogenous type 1 InsP3R channel in the outer nuclear membrane has now enabled the first comparison of the permeation and gating properties of different InsP3R isoforms in the same native membrane environment. PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Nucleoplasm transferred from mouse Itpr3. Reason: IP3R3 is a six-TM multi-pass membrane protein of the ER and nuclear envelope; a soluble nucleoplasm location is not supported by rat data and is implausible for an integral channel (at most it reflects nucleoplasmic reticulum invaginations of the envelope). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: MGI:MGI:96624 SOURCE WEAK OR INFERRED Likely an immunostaining-based nuclear call; not membrane-resolved. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt 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 PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. |
| GO:0005730 nucleolus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Nucleolus transferred from mouse Itpr3. Reason: IP3R3 is a six-TM multi-pass membrane protein of the ER and nuclear envelope; a soluble nucleolus location is not supported by rat data and is implausible for an integral channel (at most it reflects nucleoplasmic reticulum invaginations of the envelope). Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: MGI:MGI:96624 SOURCE WEAK OR INFERRED Likely an immunostaining-based nuclear call; not membrane-resolved. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt 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 PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | MODIFY | Summary: Cytoplasm transferred from mouse Itpr3. Reason: True but uninformative; the specific location is the ER membrane, already carried with direct rat evidence. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96624 SUPPORTS TRANSFER Cytoplasmic membrane location is correct but coarse. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. |
| GO:0005783 endoplasmic reticulum | IDA PMID:19116207 Functional ryanodine receptors in the plasma membrane of RIN... | ACCEPT | Summary: Sucrose-gradient fractionation of RINm5F cells places IP3R3 with calnexin. Reason: Root organelle term from a fractionation assay that co-separates IP3R3 with the ER marker calnexin and away from PMCA. The assay supports the organelle; the sub-compartment (ER membrane) is carried by other rows. Supporting Evidence: PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:19116207 Subcellular fractionation showed that type 3 IP(3) receptors (IP(3)R3) were expressed predominantly in endoplasmic reticulum |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IP3R-family mapping to ER. Reason: Root organelle term; the ER claim holds for IP3R3 (fractionation with calnexin, ER immunolocalisation, FRAP within ER membranes). The sub-compartment is carried separately. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Belongs to the InsP3 receptor family. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:8388391 Sequence and functional characterization of a third inositol... | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:10096607 Differential cellular expression of isoforms of inositol 1,4... | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) PMID:10096607 IP3R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:15533917 Functional characterization of mammalian inositol 1,4,5-tris... | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:15537642 Translational mobility of the type 3 inositol 1,4,5-trisphos... | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | ISO GO_REF:0000121 | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | ISO GO_REF:0000121 | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-RNO-182052 | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: Reactome:R-RNO-182052 The IP3 receptor (IP3R) is an IP3-gated calcium channel. PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-RNO-182097 | ACCEPT | Summary: ER membrane location of IP3R3. Reason: ER membrane is the established location of IP3R3: recombinant rat IP3R3 localises to the ER (PMID:8388391), co-fractionates with calnexin in RINm5F cells (PMID:19116207), diffuses freely in the ER membrane by FRAP (PMID:15537642, PMID:21550988), and has six C-terminal TM helices forming the pore. The channel acts here. Supporting Evidence: Reactome:R-RNO-182097 Calcium is released from the ER to the cytosol upon IP3 receptor activation PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:15537642 Here, we examined the lateral mobility of the type 3 isoform of the InsP3R (InsP3R3) in the ER membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plasma membrane pool of IP3Rs. Reason: A minor plasma-membrane pool of IP3R3 has been reported in some cell types, and PAINT placed the term at the family node. In rat cells the bulk of IP3R3 is in the ER (RINm5F fractionation separates IP3R3 from PMCA; PMID:19116207). Kept as a non-core, minor location. Supporting Evidence: PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein |
| GO:0005886 plasma membrane | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Plasma membrane pool transferred from human ITPR3. Reason: A minor plasma-membrane pool of IP3R3 has been reported in some cell types, and PAINT placed the term at the family node. In rat cells the bulk of IP3R3 is in the ER (RINm5F fractionation separates IP3R3 from PMCA; PMID:19116207). Kept as a non-core, minor location. Supporting Evidence: PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein |
| GO:0005903 brush border | IDA PMID:8288584 Primary structure, ligand binding, and localization of the h... | MARK AS OVER ANNOTATED | Summary: Brush border location from intestinal immunocytochemistry. Reason: The abstract describes ER-like staining concentrated adjacent to the apical brush border of villus cells, i.e. in the apical cytoplasm beneath the microvilli, not in the brush border itself. The apical location is captured by GO:0045177. The paper's cloning work is on human HT29 cDNA; the species of the stained intestine is not stated in the abstract. Supporting Evidence: PMID:8288584 with the highest concentration of staining occurring adjacent to the apical brush border of villus cells. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Ion transport from InterPro. Reason: Correct but general; IP3R3 mediates release of Ca2+ from the ER into the cytosol (GO:1903514). Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0006816 calcium ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Calcium ion transport from InterPro. Reason: Correct but general; refine to release of sequestered Ca2+ into the cytosol by the ER. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0006816 calcium ion transport | ISO GO_REF:0000121 | MODIFY | Summary: Calcium ion transport transferred from mouse Itpr3. Reason: Correct but general; refine to release of sequestered Ca2+ into the cytosol by the ER. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96624 SUPPORTS TRANSFER Source supports Ca2+ transport; refined. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0007186 G protein-coupled receptor signaling pathway | IDA PMID:11788349 Intracellular signal transduction during gastrin-induced his... | MODIFY | Summary: Gastrin (CCK2 receptor) signalling in ECL cells requires IP3R activation. Reason: The gastrin response is a Gq/PLC-coupled pathway in which IP3Rs perform the IP3-to-Ca2+ step (2-APB abolishes the response). The informative descendant is the PLC-activating GPCR pathway, already carried by IBA. Note the study detects IP3R1-3 transcripts and does not isolate IP3R3. Proposed replacements: phospholipase C-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:11788349 gastrin-stimulated histamine release depends on IP(3)R activation and plasmalemmal calcium entry. PMID:11788349 RT-PCR suggested the presence of inositol 1,4,5-trisphosphate receptor (IP(3)R) subtypes 1-3. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IP3R family executes the IP3-to-Ca2+ step of PLC-coupled GPCR signalling. Reason: IP3R3 performs the Ca2+ release step downstream of PLC: carbachol (muscarinic, Gq) responses in RINm5F cells, which express ~90% IP3R3, are modulated by PKA/PKC acting on IP3R3 (PMID:17373911, PMID:17320950). PAINT places this at the IP3R family node. Supporting Evidence: PMID:17373911 binding affinity and IP(3)-induced Ca2+ release activity were enhanced in permeabilized cells that were pre-treated with forskolin or PKA. PMID:17373911 RINm5F cells express almost exclusively the IP(3)R-3 subtype. PMID:17320950 whereby activated PKC dampens IP3R-3 activity |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IDA PMID:11788349 Intracellular signal transduction during gastrin-induced his... | MODIFY | Summary: IP3R-mediated rise in cytosolic Ca2+. Reason: IP3R3 is the channel that moves Ca2+ into the cytosol, not a regulator of cytosolic Ca2+ concentration; the process it executes is release of sequestered Ca2+ from the ER (GO:1903514). Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:11788349 gastrin-stimulated histamine release depends on IP(3)R activation and plasmalemmal calcium entry. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IDA PMID:17320950 Protein kinase C decreases the apparent affinity of the inos... | MODIFY | Summary: IP3R-mediated rise in cytosolic Ca2+. Reason: IP3R3 is the channel that moves Ca2+ into the cytosol, not a regulator of cytosolic Ca2+ concentration; the process it executes is release of sequestered Ca2+ from the ER (GO:1903514). Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:17320950 whereby activated PKC dampens IP3R-3 activity PMID:17320950 RINm5F cells who express almost exclusively (approximately 90%) the IP3R-3, represent an interesting model to study this particular isoform. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IDA PMID:17373911 Protein kinase A increases the binding affinity and the Ca2+... | MODIFY | Summary: IP3R-mediated rise in cytosolic Ca2+. Reason: IP3R3 is the channel that moves Ca2+ into the cytosol, not a regulator of cytosolic Ca2+ concentration; the process it executes is release of sequestered Ca2+ from the ER (GO:1903514). Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:17373911 binding affinity and IP(3)-induced Ca2+ release activity were enhanced in permeabilized cells that were pre-treated with forskolin or PKA. PMID:17373911 RINm5F cells express almost exclusively the IP(3)R-3 subtype. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0007613 memory | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Memory transferred from a mouse Itpr3 mutant phenotype. Reason: The ISO rests on a mouse mutant phenotype (acts_upstream_of_or_within). IP3R3 is a minor neuronal subtype (IP3R1 dominates in neurons); a behavioural/plasticity phenotype is a downstream consequence of altered Ca2+ signalling, not a process IP3R3 executes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:96624 SUPPORTS SOURCE BUT NOT TARGET Mutant phenotype; transfers a remote organismal consequence rather than a channel role. Supporting Evidence: PMID:17471556 The Type I inositol-1,4,5 trisphosphate receptor (InsP(3)R1) is the main InsP(3)R subtype in neurons. |
| GO:0008270 zinc ion binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Structural zinc site. Reason: UniProt annotates a Zn(2+)-binding site in the C-terminal cytoplasmic linker by similarity to human ITPR3 cryo-EM structures; a structural metal site, not the channel's function. Non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt ligand="Zn(2+)" |
| GO:0008270 zinc ion binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Structural zinc site. Reason: UniProt annotates a Zn(2+)-binding site in the C-terminal cytoplasmic linker by similarity to human ITPR3 cryo-EM structures; a structural metal site, not the channel's function. Non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt ligand="Zn(2+)" |
| GO:0015085 calcium ion transmembrane transporter activity | TAS PMID:11788349 Intracellular signal transduction during gastrin-induced his... | MODIFY | Summary: Ca2+ transmembrane transporter activity stated for IP3Rs in ECL cells. Reason: True but general (an ancestor of GO:0005220). The ECL-cell paper shows IP3R-dependent Ca2+ signalling but does not resolve subtypes; the precise activity of IP3R3 is the IP3-gated Ca2+ channel. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:11788349 gastrin-stimulated histamine release depends on IP(3)R activation and plasmalemmal calcium entry. PMID:11788349 RT-PCR suggested the presence of inositol 1,4,5-trisphosphate receptor (IP(3)R) subtypes 1-3. PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0015278 intracellularly gated calcium channel activity | ISO GO_REF:0000121 | MODIFY | Summary: Intracellularly gated Ca2+ channel activity. Reason: Correct parent term; refine to the IP3-gated channel term GO:0005220, already carried with direct rat evidence. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96624 SUPPORTS TRANSFER Source supports the channel activity; only the granularity is refined. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0015278 intracellularly gated calcium channel activity | ISO GO_REF:0000121 | MODIFY | Summary: Intracellularly gated Ca2+ channel activity. Reason: Correct parent term; refine to the IP3-gated channel term GO:0005220, already carried with direct rat evidence. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q14573 SUPPORTS TRANSFER Source supports the channel activity; only the granularity is refined. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0015278 intracellularly gated calcium channel activity | ISS GO_REF:0000024 | MODIFY | Summary: Intracellularly gated Ca2+ channel activity. Reason: Correct parent term; refine to the IP3-gated channel term GO:0005220, already carried with direct rat evidence. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P70227 SUPPORTS TRANSFER Source supports the channel activity; only the granularity is refined. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Membrane from InterPro. Reason: True but general; the specific membrane is the ER membrane, already carried. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) |
| GO:0016324 apical plasma membrane | IDA PMID:18005397 Characterization of ryanodine receptors in rat colonic epith... | KEEP AS NON CORE | Summary: Apical location of IP3R3 in rat colonic epithelium. Reason: The cached abstract shows IP3R3 is the dominant IP3R in rat colonic epithelium but does not describe the apical result; apical concentration of IP3R3 in polarised secretory epithelia is well documented and the curator read the full text. Whether this is apical plasma membrane or sub-apical ER cannot be checked here. Non-core. Supporting Evidence: PMID:18005397 A double staining with IP(3)R3, the dominant cytoplasmic isoform of IP3Rs in this epithelium |
| GO:0016529 sarcoplasmic reticulum | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Sarcoplasmic reticulum from the IP3R family node. Reason: The SR is the muscle form of the ER; IP3Rs are present there in smooth and skeletal muscle. For IP3R3 the claim is plausible but tissue-specific. Non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0019722 calcium-mediated signaling | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Calcium-mediated signalling inferred from the channel activity. Reason: IP3R3 generates the Ca2+ signal; downstream calcium-mediated signalling is executed by Ca2+ sensors. Non-core. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0030168 platelet activation | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Platelet activation transferred from human ITPR3. Reason: IP3Rs release Ca2+ from the platelet dense tubular system during agonist-induced activation; IP3R3 contributes the Ca2+ release step. Cell-type-specific, non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0030425 dendrite | IDA PMID:17471556 Inositol 1,4,5 trisphosphate receptor and chromogranin B are... | UNDECIDED | Summary: Dendritic IP3R immunoreactivity in rat hippocampus. Reason: The cached abstract (full text not retrievable from PMC) describes InsP3R1 as the main neuronal subtype and does not mention IP3R3; whether the full text stained IP3R3 in dendrites cannot be verified here. Supporting Evidence: PMID:17471556 The Type I inositol-1,4,5 trisphosphate receptor (InsP(3)R1) is the main InsP(3)R subtype in neurons. |
| GO:0030658 transport vesicle membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Transport vesicle membrane from UniProt subcellular location (secretory vesicle, by similarity to bovine). Reason: The UniProt secretory-vesicle location is by similarity to a bovine IP3R3 report; secretory-granule IP3Rs are contentious and rat data place IP3R3 in the ER membrane. Supporting Evidence: PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:8388391 Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum. |
| GO:0030667 secretory granule membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Secretory granule membrane from the IP3R family node. Reason: Secretory-granule localisation of IP3Rs is contentious; the IBA rests on human/bovine reports while rat IP3R3 co-fractionates with the ER marker calnexin. The neuronal-terminal enrichment near dense-core vesicles (PMID:10096607) does not show granule-membrane residence. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q14643 SOURCE WEAK OR INFERRED Granule localisation reports are disputed. UniProtKB:Q8WN96 SOURCE WEAK OR INFERRED Granule localisation reports are disputed. Supporting Evidence: PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein PMID:10096607 IP3R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) |
| GO:0035091 phosphatidylinositol binding | IBA GO_REF:0000033 | MODIFY | Summary: Phosphatidylinositol binding placed at the IP3R family node. Reason: GO:0035091 is binding of inositol-containing glycerophospholipids. The ligand of IP3R3 is the soluble second messenger IP3 (and, at lower affinity, other inositol polyphosphates), captured by GO:0070679, which the gene already carries with direct rat evidence. No study shows IP3R3 binding phosphatidylinositol lipids. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN001010185 SOURCE BAD Node-level term conflates IP3 (soluble) with phosphoinositide lipid binding. Proposed replacements: inositol 1,4,5 trisphosphate binding Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. PMID:15533917 followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM) file:rat/Itpr3/Itpr3-uniprot.txt ligand="1D-myo-inositol 1,4,5-trisphosphate" |
| GO:0035091 phosphatidylinositol binding | ISO GO_REF:0000121 | MODIFY | Summary: Phosphatidylinositol binding transferred from mouse Itpr3. Reason: GO:0035091 is binding of inositol-containing glycerophospholipids. The ligand of IP3R3 is the soluble second messenger IP3 (and, at lower affinity, other inositol polyphosphates), captured by GO:0070679, which the gene already carries with direct rat evidence. No study shows IP3R3 binding phosphatidylinositol lipids. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:96624 SOURCE BAD Source term conflates IP3 binding with phosphoinositide lipid binding. Proposed replacements: inositol 1,4,5 trisphosphate binding Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. PMID:15533917 followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM) file:rat/Itpr3/Itpr3-uniprot.txt ligand="1D-myo-inositol 1,4,5-trisphosphate" |
| GO:0042802 identical protein binding | IPI PMID:10694253 Single-channel properties in endoplasmic reticulum membrane ... | KEEP AS NON CORE | Summary: Self-association of rat IP3R3 subunits. Reason: Recombinant rat IP3R3 forms homotetramers (and heterotetramers with endogenous Xenopus IP3R1) in oocytes; self-association reflects channel assembly. Structural, non-core. Supporting Evidence: PMID:10694253 were contributed by homotetramers of r-InsP3R-3 monomers PMID:10694253 These experimental results suggest that the Xenopus type 1 and rat type 3 InsP3R isoforms may form heterotetrameric complexes in oocytes. |
| GO:0043025 neuronal cell body | IDA PMID:17091480 Signaling proteins in the axoglial apparatus of sciatic nerv... | UNDECIDED | Summary: Neuronal cell body immunostaining in sciatic nerve study. Reason: The cached abstract describes IP3R3 as the predominant isoform in Schwann cells and does not report neuronal soma staining; full text not available to verify. Supporting Evidence: PMID:17091480 IP(3)R3 is the most predominant isoform in Schwann cells, and is expressed in particularly dense patches in the paranodal region. |
| GO:0043235 signaling receptor complex | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Signaling receptor complex transferred from human ITPR3. Reason: The IP3 receptor is itself a homotetrameric receptor complex for IP3; GO has no IP3 receptor complex term. Kept as non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Homotetramer (By similarity). Reactome:R-RNO-182052 The IP3 receptor (IP3R) is an IP3-gated calcium channel. |
| GO:0043533 inositol 1,3,4,5 tetrakisphosphate binding | IDA PMID:8388391 Sequence and functional characterization of a third inositol... | KEEP AS NON CORE | Summary: Recombinant rat IP3R3 binds inositol 1,3,4,5-tetrakisphosphate. Reason: InsP4 competes at the IP3 site with lower affinity; not a physiological agonist. Non-core. Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. |
| GO:0044877 protein-containing complex binding | IDA PMID:10694253 Single-channel properties in endoplasmic reticulum membrane ... | KEEP AS NON CORE | Summary: Association of rat IP3R3 with endogenous Xenopus IP3R1 tetrameric complexes. Reason: Co-immunoprecipitation showed rat IP3R3 can join heterotetrameric IP3R complexes; a structural property, non-core. Supporting Evidence: PMID:10694253 These experimental results suggest that the Xenopus type 1 and rat type 3 InsP3R isoforms may form heterotetrameric complexes in oocytes. |
| GO:0045177 apical part of cell | IDA PMID:8288584 Primary structure, ligand binding, and localization of the h... | KEEP AS NON CORE | Summary: Apical concentration of IP3R3 in intestinal villus cells. Reason: Staining was highest in the apical cytoplasm adjacent to the brush border, consistent with the apical ER pool of IP3R3 typical of polarised epithelia. Cell-type-specific, non-core. Supporting Evidence: PMID:8288584 with the highest concentration of staining occurring adjacent to the apical brush border of villus cells. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:21550988 Differential distribution, clustering, and lateral diffusion... | KEEP AS NON CORE | Summary: Perinuclear distribution of expressed rat IP3R3 in COS-7 cells. Reason: IP3R3 is uniformly distributed in ER membranes and behaves similarly in perinuclear and peripheral regions; the perinuclear signal reflects the ER. Non-core. Supporting Evidence: PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER) PMID:21550988 whereas IP(3)R3 behaved similarly in both regions |
| GO:0050913 sensory perception of bitter taste | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Sensory perception of bitter taste transferred from mouse Itpr3. Reason: IP3R3 is the IP3R of type II taste receptor cells, where it executes the Ca2+ release step of the T1R/T2R-gustducin-PLCbeta2 cascade (mouse knockout data). The channel does part of the work of taste transduction, so the transfer is reasonable, but it is tissue-specific and non-core. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0050916 sensory perception of sweet taste | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Sensory perception of sweet taste transferred from mouse Itpr3. Reason: IP3R3 is the IP3R of type II taste receptor cells, where it executes the Ca2+ release step of the T1R/T2R-gustducin-PLCbeta2 cascade (mouse knockout data). The channel does part of the work of taste transduction, so the transfer is reasonable, but it is tissue-specific and non-core. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0050917 sensory perception of umami taste | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Sensory perception of umami taste transferred from mouse Itpr3. Reason: IP3R3 is the IP3R of type II taste receptor cells, where it executes the Ca2+ release step of the T1R/T2R-gustducin-PLCbeta2 cascade (mouse knockout data). The channel does part of the work of taste transduction, so the transfer is reasonable, but it is tissue-specific and non-core. Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0051209 release of sequestered calcium ion into cytosol | IBA GO_REF:0000033 | MODIFY | Summary: Release of sequestered Ca2+ into cytosol. Reason: Correct, but IP3R3 releases Ca2+ specifically from the ER store; refine to GO:1903514 (an is_a descendant). Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008550777 SUPPORTS TRANSFER Node correctly captures Ca2+ release; refined to the ER-specific child. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0051209 release of sequestered calcium ion into cytosol | ISO GO_REF:0000121 | MODIFY | Summary: Release of sequestered Ca2+ into cytosol (from human ITPR3). Reason: Correct, but IP3R3 releases Ca2+ specifically from the ER store; refine to GO:1903514 (an is_a descendant). Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q14573 SUPPORTS TRANSFER Source supports Ca2+ release; refined. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0051289 protein homotetramerization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Homotetramer assembly. Reason: Tetramer assembly forms the channel pore; rat IP3R3 forms homotetramers in oocytes (PMID:10694253). Structural prerequisite, non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Homotetramer (By similarity). PMID:10694253 were contributed by homotetramers of r-InsP3R-3 monomers |
| GO:0051289 protein homotetramerization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Homotetramer assembly. Reason: Tetramer assembly forms the channel pore; rat IP3R3 forms homotetramers in oocytes (PMID:10694253). Structural prerequisite, non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Homotetramer (By similarity). PMID:10694253 were contributed by homotetramers of r-InsP3R-3 monomers |
| GO:0051592 response to calcium ion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Response to calcium ion transferred from human ITPR3. Reason: Biphasic Ca2+ regulation of gating is an activity-regulation property of the channel (captured by Ca2+ binding), not a cellular response process executed by IP3R3. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q14573 SUPPORTS SOURCE BUT NOT TARGET Channel regulation by Ca2+ conflated with a response-to-stimulus process. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt Inositol 1,4,5-trisphosphate-gated calcium channel is regulated by cytosolic calcium in a biphasic manner. |
| GO:0055074 calcium ion homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Calcium ion homeostasis. Reason: UniProt (by similarity) states IP3R3 Ca2+ release participates in cellular Ca2+ homeostasis; true but downstream of the core release process. Non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasis |
| GO:0055074 calcium ion homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Calcium ion homeostasis. Reason: UniProt (by similarity) states IP3R3 Ca2+ release participates in cellular Ca2+ homeostasis; true but downstream of the core release process. Non-core. Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasis |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Transmembrane transport from InterPro. Reason: Correct but general; refine to the ER Ca2+ release process. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0060291 long-term synaptic potentiation | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Long-term synaptic potentiation transferred from a mouse Itpr3 mutant phenotype. Reason: The ISO rests on a mouse mutant phenotype (acts_upstream_of_or_within). IP3R3 is a minor neuronal subtype (IP3R1 dominates in neurons); a behavioural/plasticity phenotype is a downstream consequence of altered Ca2+ signalling, not a process IP3R3 executes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:96624 SUPPORTS SOURCE BUT NOT TARGET Mutant phenotype; transfers a remote organismal consequence rather than a channel role. Supporting Evidence: PMID:17471556 The Type I inositol-1,4,5 trisphosphate receptor (InsP(3)R1) is the main InsP(3)R subtype in neurons. |
| GO:0070588 calcium ion transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Calcium ion transmembrane transport from InterPro. Reason: Correct but general; IP3R3 moves Ca2+ across the ER membrane into the cytosol, captured by GO:1903514 (an is_a descendant). Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 for all three mammalian InsP3R isoforms the size of the unitary current is 1.9 pA and single-channel conductance is 74-80 pS PMID:15533917 Here we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:10694253 Here, we describe functional expression and single-channel recording of recombinant rat InsP(3)R-3 in its native membrane environment. file:rat/Itpr3/Itpr3-uniprot.txt 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 |
| GO:0070679 inositol 1,4,5 trisphosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: IP3 binding by the IP3-binding core. Reason: IP3 binding by the N-terminal binding core is intrinsic to channel gating: recombinant rat IP3R3 binds IP3 (PMID:8388391), its apparent IP3 affinity is 0.40 microM in bilayers (PMID:15533917), and PKA increases its IP3-binding affinity in RINm5F cells (PMID:17373911). Accepted as the ligand-binding component of the core activity. Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. PMID:15533917 followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM) file:rat/Itpr3/Itpr3-uniprot.txt ligand="1D-myo-inositol 1,4,5-trisphosphate" |
| GO:0070679 inositol 1,4,5 trisphosphate binding | IDA PMID:17320950 Protein kinase C decreases the apparent affinity of the inos... | ACCEPT | Summary: IP3 binding by the IP3-binding core. Reason: IP3 binding by the N-terminal binding core is intrinsic to channel gating: recombinant rat IP3R3 binds IP3 (PMID:8388391), its apparent IP3 affinity is 0.40 microM in bilayers (PMID:15533917), and PKA increases its IP3-binding affinity in RINm5F cells (PMID:17373911). Accepted as the ligand-binding component of the core activity. Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. PMID:15533917 followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM) file:rat/Itpr3/Itpr3-uniprot.txt ligand="1D-myo-inositol 1,4,5-trisphosphate" |
| GO:0070679 inositol 1,4,5 trisphosphate binding | IDA PMID:17373911 Protein kinase A increases the binding affinity and the Ca2+... | ACCEPT | Summary: IP3 binding by the IP3-binding core. Reason: IP3 binding by the N-terminal binding core is intrinsic to channel gating: recombinant rat IP3R3 binds IP3 (PMID:8388391), its apparent IP3 affinity is 0.40 microM in bilayers (PMID:15533917), and PKA increases its IP3-binding affinity in RINm5F cells (PMID:17373911). Accepted as the ligand-binding component of the core activity. Supporting Evidence: PMID:17373911 binding affinity and IP(3)-induced Ca2+ release activity were enhanced in permeabilized cells that were pre-treated with forskolin or PKA. PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. PMID:15533917 followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM) file:rat/Itpr3/Itpr3-uniprot.txt ligand="1D-myo-inositol 1,4,5-trisphosphate" |
| GO:0070679 inositol 1,4,5 trisphosphate binding | IEA GO_REF:0000120 | ACCEPT | Summary: IP3 binding by the IP3-binding core. Reason: IP3 binding by the N-terminal binding core is intrinsic to channel gating: recombinant rat IP3R3 binds IP3 (PMID:8388391), its apparent IP3 affinity is 0.40 microM in bilayers (PMID:15533917), and PKA increases its IP3-binding affinity in RINm5F cells (PMID:17373911). Accepted as the ligand-binding component of the core activity. Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. PMID:15533917 followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM) file:rat/Itpr3/Itpr3-uniprot.txt ligand="1D-myo-inositol 1,4,5-trisphosphate" |
| GO:0070679 inositol 1,4,5 trisphosphate binding | ISO GO_REF:0000121 | ACCEPT | Summary: IP3 binding by the IP3-binding core. Reason: IP3 binding by the N-terminal binding core is intrinsic to channel gating: recombinant rat IP3R3 binds IP3 (PMID:8388391), its apparent IP3 affinity is 0.40 microM in bilayers (PMID:15533917), and PKA increases its IP3-binding affinity in RINm5F cells (PMID:17373911). Accepted as the ligand-binding component of the core activity. Supporting Evidence: PMID:8388391 Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate. PMID:15533917 followed by InsP3R1 (0.27 microM), and then by InsP3R3 (0.40 microM) file:rat/Itpr3/Itpr3-uniprot.txt ligand="1D-myo-inositol 1,4,5-trisphosphate" |
| GO:0071320 cellular response to cAMP | IDA PMID:20189985 Regulation of inositol 1,4,5-trisphosphate receptors by cAMP... | KEEP AS NON CORE | Summary: cAMP sensitises rat IP3R3 to IP3 independently of PKA in DT40 cells. Reason: DT40 cells expressing only rat IP3R3 showed cAMP-induced sensitisation to IP3 without PKA; a regulatory input to the channel. Non-core. Supporting Evidence: PMID:20189985 Using DT40 cells expressing single subtypes of mammalian IP(3)R, we demonstrate that high concentrations of cAMP similarly sensitize all IP(3)R isoforms to IP(3) by a mechanism that does not require cAMP-dependent protein kinase (PKA). |
| GO:0098554 cytoplasmic side of endoplasmic reticulum membrane | ISO GO_REF:0000121 | MODIFY | Summary: Cytoplasmic side of ER membrane transferred from mouse Itpr3. Reason: IP3R3 is an integral multi-pass protein with a large cytoplasmic domain; leaflet terms describe peripheral proteins. The appropriate location is the ER membrane itself, already carried. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96624 SUPPORTS TRANSFER Location is correct at the level of the ER membrane. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:rat/Itpr3/Itpr3-uniprot.txt 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 PMID:19116207 IP3R3 appeared in the same fractions as calnexin, an integral ER protein |
| GO:0098793 presynapse | IDA PMID:10096607 Differential cellular expression of isoforms of inositol 1,4... | KEEP AS NON CORE | Summary: IP3R3 enriched in neuronal terminals in rat forebrain. Reason: Isoform-specific antibodies show IP3R3 enriched in neuronal terminals in limbic and basal forebrain; a neuronal location, non-core. Supporting Evidence: PMID:10096607 IP3R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) |
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Download this section (compressed HTML)Q: Does a functional plasma-membrane pool of IP3R3 exist in native rat cells (e.g. beta-cells, colonic or biliary epithelium), or do apical/plasma membrane annotations reflect sub-apical ER?
Q: The IBA/ISO phosphatidylinositol binding (GO:0035091) on IP3R family members appears to conflate soluble IP3 with phosphoinositide lipids; should the PAINT node assertion be withdrawn in favour of inositol 1,4,5 trisphosphate binding?
Q: Do the rat IDA rows for dendrite (PMID:17471556) and neuronal cell body (PMID:17091480) rest on IP3R3-specific antibodies, given that both abstracts foreground other subtypes or Schwann cells?
Experiment: Immuno-EM or expansion microscopy of IP3R3 with ER (calnexin) and apical plasma-membrane markers in rat colonic crypts and cholangiocytes, combined with surface biotinylation.
Hypothesis: IP3R3 at the apical pole of polarised rat epithelia resides in sub-apical ER rather than the apical plasma membrane.
Type: localization
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