Itpr1 encodes the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1), a large (2,750-residue) multi-pass membrane protein that assembles into homo- or heterotetrameric ligand-gated Ca2+ release channels in the endoplasmic reticulum membrane and nuclear envelope. Binding of the second messenger IP3, produced by phospholipase C downstream of G protein-coupled and tyrosine kinase receptors, together with cytosolic Ca2+ (biphasic activation and inhibition) and ATP opens a six-transmembrane-helix pore per subunit, releasing Ca2+ from the ER lumen into the cytosol and nucleoplasm. Channel sensitivity is tuned by cAMP, PKA phosphorylation and many binding partners (e.g. calmodulin, IRBIT, Bcl-2/calcineurin, 4.1N, huntingtin/HAP1). IP3R1 is the predominant neuronal subtype, especially abundant in cerebellar Purkinje cells, and at ER-mitochondria contacts it couples to VDAC1 through GRP75 to supply Ca2+ to mitochondria. IP3R1-mediated Ca2+ signals contribute to synaptic Ca2+ dynamics, motor coordination, egg activation, hepatocyte proliferation during liver regeneration and Ca2+-dependent cell death.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000902 cell morphogenesis | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Cell morphogenesis transferred from a mouse Itpr1 mutant phenotype. Reason: IP3R1 is a Ca2+ release channel; any effect on cell shape (e.g. Purkinje dendrite morphology in mutant mice) is a downstream consequence of altered Ca2+ signalling, not a process the channel executes. The term is too remote from the gene product activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:96623 SUPPORTS SOURCE BUT NOT TARGET Mouse mutant phenotype; transfers a downstream morphological consequence rather than a channel role. Supporting Evidence: UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0001666 response to hypoxia | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Response to hypoxia based on hypoxia-induced changes in IP3R1 expression. Reason: The evidence is induction of Itpr1 mRNA/protein by hypoxia, an expression response rather than participation of IP3R1 in a hypoxia-sensing or adaptive process. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: MGI:MGI:96623 SOURCE WEAK OR INFERRED Hypoxia response rests on expression changes. Supporting Evidence: PMID:17285299 gene expression of types 1 and 2 IP(3) receptors is significantly increased after the exposure of mice to hypoxic stimulus for 6 h and also in rat cerebellar granular cells |
| GO:0001666 response to hypoxia | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Response to hypoxia based on hypoxia-induced changes in IP3R1 expression. Reason: The evidence is induction of Itpr1 mRNA/protein by hypoxia, an expression response rather than participation of IP3R1 in a hypoxia-sensing or adaptive process. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q14643 SOURCE WEAK OR INFERRED Hypoxia response rests on expression changes. Supporting Evidence: PMID:17285299 gene expression of types 1 and 2 IP(3) receptors is significantly increased after the exposure of mice to hypoxic stimulus for 6 h and also in rat cerebellar granular cells |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic ion channel activity from InterPro; IP3R1 is specifically an IP3-gated Ca2+ channel. Reason: Correct but general; the specific child term GO:0005220 is experimentally supported for rat IP3R1 and already carried by the gene. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity is the defining molecular function of IP3R1. Reason: Rat IP3R1 channel activity has been recorded directly in planar bilayers and by on-nucleus patch clamp of IP3R-null DT40 cells expressing rat IP3R1, and the rat channel structure resolves the IP3, Ca2+ and ATP sites that gate the pore. All evidence lines for this term agree. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| 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 is the defining molecular function of IP3R1. Reason: Rat IP3R1 channel activity has been recorded directly in planar bilayers and by on-nucleus patch clamp of IP3R-null DT40 cells expressing rat IP3R1, and the rat channel structure resolves the IP3, Ca2+ and ATP sites that gate the pore. All evidence lines for this term agree. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IDA PMID:19036964 Deranged calcium signaling and neurodegeneration in spinocer... | ACCEPT | Summary: IP3R1 channel activity measured in bilayers, sensitised by mutant ataxin-3. Reason: Planar-bilayer recordings of IP3R1 activation by IP3 (here sensitised by ATX3exp) directly assay the IP3-gated channel. Supporting Evidence: PMID:19036964 InsP(3)R1 was sensitized to activation by InsP(3) in the presence of mutant ATX3(exp) PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IDA PMID:22547632 Differential regulation of the InsP₃ receptor type-1 and -2 ... | ACCEPT | Summary: IP3-gated Ca2+ release channel activity is the defining molecular function of IP3R1. Reason: Rat IP3R1 channel activity has been recorded directly in planar bilayers and by on-nucleus patch clamp of IP3R-null DT40 cells expressing rat IP3R1, and the rat channel structure resolves the IP3, Ca2+ and ATP sites that gate the pore. All evidence lines for this term agree. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity is the defining molecular function of IP3R1. Reason: Rat IP3R1 channel activity has been recorded directly in planar bilayers and by on-nucleus patch clamp of IP3R-null DT40 cells expressing rat IP3R1, and the rat channel structure resolves the IP3, Ca2+ and ATP sites that gate the pore. All evidence lines for this term agree. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | ISO GO_REF:0000121 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity is the defining molecular function of IP3R1. Reason: Rat IP3R1 channel activity has been recorded directly in planar bilayers and by on-nucleus patch clamp of IP3R-null DT40 cells expressing rat IP3R1, and the rat channel structure resolves the IP3, Ca2+ and ATP sites that gate the pore. All evidence lines for this term agree. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | ISO GO_REF:0000121 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity is the defining molecular function of IP3R1. Reason: Rat IP3R1 channel activity has been recorded directly in planar bilayers and by on-nucleus patch clamp of IP3R-null DT40 cells expressing rat IP3R1, and the rat channel structure resolves the IP3, Ca2+ and ATP sites that gate the pore. All evidence lines for this term agree. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity | ISS GO_REF:0000024 | ACCEPT | Summary: IP3-gated Ca2+ release channel activity is the defining molecular function of IP3R1. Reason: Rat IP3R1 channel activity has been recorded directly in planar bilayers and by on-nucleus patch clamp of IP3R-null DT40 cells expressing rat IP3R1, and the rat channel structure resolves the IP3, Ca2+ and ATP sites that gate the pore. All evidence lines for this term agree. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005262 calcium channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic calcium channel activity from InterPro. 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 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IP3R1 binds Ca2+ at regulatory activation/inhibition sites. Reason: Ca2+ is a co-agonist with biphasic regulation of channel opening; the rat IP3R1 cryo-EM structure shows Ca2+ densities at the predicted regulatory sites. Real but regulatory, so non-core. Supporting Evidence: PMID:36376291 A comparison of the cryo-EM density maps of Ca-IP3R1 and apo-IP3R1 revealed strong non-protein densities in Ca-IP3R1 structure at locations consistent with putative Ca2+-binding sites PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells |
| GO:0005515 protein binding | IPI PMID:12873381 Huntingtin and huntingtin-associated protein 1 influence neu... | REMOVE | Summary: Bare protein binding annotation for the IP3R1 interaction with human huntingtin (HTT). Reason: The interaction with human huntingtin (HTT) is reported and modulates IP3R1 Ca2+ release, but the bare GO:0005515 term carries no functional information. Removed under the protein-binding policy; removal does not dispute the interaction. Supporting Evidence: PMID:12873381 We show that an InsP3R1-HAP1A-Htt ternary complex is formed in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:12873381 Huntingtin and huntingtin-associated protein 1 influence neu... | REMOVE | Summary: Bare protein binding annotation for the IP3R1 interaction with rat huntingtin. Reason: The interaction with rat huntingtin is reported and modulates IP3R1 Ca2+ release, but the bare GO:0005515 term carries no functional information. Removed under the protein-binding policy; removal does not dispute the interaction. Supporting Evidence: PMID:12873381 We show that an InsP3R1-HAP1A-Htt ternary complex is formed in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:12873381 Huntingtin and huntingtin-associated protein 1 influence neu... | REMOVE | Summary: Bare protein binding annotation for the IP3R1 interaction with HAP1A. Reason: The interaction with HAP1A is reported and modulates IP3R1 Ca2+ release, but the bare GO:0005515 term carries no functional information. Removed under the protein-binding policy; removal does not dispute the interaction. Supporting Evidence: PMID:12873381 We show that an InsP3R1-HAP1A-Htt ternary complex is formed in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:12873381 Huntingtin and huntingtin-associated protein 1 influence neu... | REMOVE | Summary: Bare protein binding annotation for the IP3R1 interaction with HAP1B. Reason: The interaction with HAP1B is reported and modulates IP3R1 Ca2+ release, but the bare GO:0005515 term carries no functional information. Removed under the protein-binding policy; removal does not dispute the interaction. Supporting Evidence: PMID:12873381 We show that an InsP3R1-HAP1A-Htt ternary complex is formed in vitro and in vivo. |
| GO:0005515 protein binding | IPI PMID:17178908 Chaperone-mediated coupling of endoplasmic reticulum and mit... | REMOVE | Summary: Bare protein binding annotation for the IP3R1 interaction with VDAC1 and GRP75 (HSPA9). Reason: The interaction with VDAC1 and GRP75 (HSPA9) is reported and modulates IP3R1 Ca2+ release, but the bare GO:0005515 term carries no functional information. Removed under the protein-binding policy; removal does not dispute the interaction. Supporting Evidence: PMID:17178908 We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca(2+)-release channel inositol 1,4,5-trisphosphate receptor (IP(3)R) through the molecular chaperone glucose-regulated protein 75 (grp75). |
| GO:0005515 protein binding | IPI PMID:21424589 Inositol 1, 4, 5-trisphosphate receptor interacts with the S... | MODIFY | Summary: Protein binding to syntaxin 1B, a SNARE protein. Reason: The paper maps a direct interaction of the syntaxin 1B SNARE domain with the IP3R1 internal coupling domain, so the informative MF is SNARE binding rather than bare protein binding. Proposed replacements: SNARE binding Supporting Evidence: PMID:21424589 We found that a SNARE-domain of Syx1B, one of the two Syx1 isoforms, directly interacted with the type1 IP(3)R (IP(3)R1) internal coupling domain |
| GO:0005515 protein binding | IPI PMID:22045699 The homocysteine-inducible endoplasmic reticulum (ER) stress... | REMOVE | Summary: Bare protein binding annotation for the IP3R1 interaction with Herp. Reason: The interaction with Herp is reported and modulates IP3R1 Ca2+ release, but the bare GO:0005515 term carries no functional information. Removed under the protein-binding policy; removal does not dispute the interaction. Supporting Evidence: PMID:22045699 Herp plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca(2+) release channels |
| GO:0005524 ATP binding | IDA PMID:36376291 Conformational motions and ligand-binding underlying gating ... | KEEP AS NON CORE | Summary: ATP binding at a regulatory site of rat IP3R1, resolved by cryo-EM. Reason: The cryo-EM structure locates an ATP-binding site in rat IP3R1 and ATP potentiates gating; this is a modulatory ligand, not the core activity. Supporting Evidence: PMID:36376291 The CIA-IP3R1 structure reveals a previously unseen ATP-binding site located at the interface between the ILD and LNK domains PMID:15533917 InsP3R1 has a high-affinity (0.13 mM) ATP modulatory site |
| GO:0005635 nuclear envelope | IDA PMID:16014380 Nuclear inositol 1,4,5-trisphosphate receptors regulate loca... | ACCEPT | Summary: IP3R1 is located in the nuclear envelope of rat myotubes. Reason: Immunofluorescence/immuno-EM of rat myotube nuclei places IP3R1 preferentially in the inner nuclear membrane, and isolated nuclei release Ca2+ in response to IP3; the nuclear envelope is continuous with the ER. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane PMID:16014380 Isolated nuclei responded to IP(3) with rapid and transient Ca(2+) concentration elevations |
| GO:0005635 nuclear envelope | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 is located in the nuclear envelope of rat myotubes. Reason: Immunofluorescence/immuno-EM of rat myotube nuclei places IP3R1 preferentially in the inner nuclear membrane, and isolated nuclei release Ca2+ in response to IP3; the nuclear envelope is continuous with the ER. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane PMID:16014380 Isolated nuclei responded to IP(3) with rapid and transient Ca(2+) concentration elevations |
| GO:0005637 nuclear inner membrane | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 is in the inner nuclear membrane. Reason: Consistent with rat myotube immuno-EM showing IP3R1 preferentially in the inner nuclear membrane, where it releases nuclear Ca2+. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane PMID:16014380 Isolated nuclei responded to IP(3) with rapid and transient Ca(2+) concentration elevations |
| GO:0005730 nucleolus | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Nucleolus location transferred from mouse. Reason: IP3R1 is a multi-pass membrane protein of the ER and nuclear envelope; a nucleolar location is not supported by the rat literature and is implausible for an integral membrane channel. Nuclear-envelope localisation is captured by other rows. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: MGI:MGI:96623 SOURCE WEAK OR INFERRED Nucleolar location implausible for a multi-pass ER/nuclear-envelope channel. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | MODIFY | Summary: Cytoplasm location; IP3R1 is an integral ER membrane protein. Reason: True but uninformative; the specific location is ER membrane, already carried with direct evidence. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96623 SUPPORTS TRANSFER Cytoplasm is true but general; ER membrane is the informative location. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | ACCEPT | Summary: IP3R1 is an ER-resident Ca2+ release channel. Reason: Root organelle term; the ER claim is sound (IP3R family signature, rat targeting and FRAP data). The sub-compartment (ER membrane) is carried separately. Supporting Evidence: PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 is an ER-resident Ca2+ release channel. Reason: Root organelle term; the ER claim is sound (IP3R family signature, rat targeting and FRAP data). The sub-compartment (ER membrane) is carried separately. Supporting Evidence: PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005783 endoplasmic reticulum | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 is an ER-resident Ca2+ release channel. Reason: Root organelle term; the ER claim is sound (IP3R family signature, rat targeting and FRAP data). The sub-compartment (ER membrane) is carried separately. Supporting Evidence: PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IP3R1 is an integral membrane protein of the ER, where it acts as the Ca2+ release channel. Reason: Rat IP3R1 topology, TMD1-mediated ER targeting and uniform ER-membrane distribution with free lateral diffusion all place it in the ER membrane, where its channel activity operates. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:10506212 Subunit oligomerization, and topology of the inositol 1,4, 5... | ACCEPT | Summary: IP3R1 is an integral membrane protein of the ER, where it acts as the Ca2+ release channel. Reason: Rat IP3R1 topology, TMD1-mediated ER targeting and uniform ER-membrane distribution with free lateral diffusion all place it in the ER membrane, where its channel activity operates. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:15533917 Functional characterization of mammalian inositol 1,4,5-tris... | ACCEPT | Summary: IP3R1 is an integral membrane protein of the ER, where it acts as the Ca2+ release channel. Reason: Rat IP3R1 topology, TMD1-mediated ER targeting and uniform ER-membrane distribution with free lateral diffusion all place it in the ER membrane, where its channel activity operates. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:15911880 Junctional membrane inositol 1,4,5-trisphosphate receptor co... | ACCEPT | Summary: IP3R1 in ER membranes, including junctional ER beneath the plasma membrane of rat chromaffin cells. Reason: Immuno-EM in rat chromaffin cells places IP3R1 on the Ca2+ store membrane juxtaposed to the plasma membrane. Supporting Evidence: PMID:15911880 it couples the plasmalemmal EGFR with IP(3)R1 at the Ca(2+) store located juxtaposed to the plasma membrane PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: IP3R1 is an integral membrane protein of the ER, where it acts as the Ca2+ release channel. Reason: Rat IP3R1 topology, TMD1-mediated ER targeting and uniform ER-membrane distribution with free lateral diffusion all place it in the ER membrane, where its channel activity operates. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 is an integral membrane protein of the ER, where it acts as the Ca2+ release channel. Reason: Rat IP3R1 topology, TMD1-mediated ER targeting and uniform ER-membrane distribution with free lateral diffusion all place it in the ER membrane, where its channel activity operates. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 is an integral membrane protein of the ER, where it acts as the Ca2+ release channel. Reason: Rat IP3R1 topology, TMD1-mediated ER targeting and uniform ER-membrane distribution with free lateral diffusion all place it in the ER membrane, where its channel activity operates. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:19845505 Hydrophobic residues within TMD1 and TMD2 then ensure stable association with the ER membrane. PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-RNO-182052 | ACCEPT | Summary: Reactome places IP3R1 in the ER membrane in the IP3-mediated Ca2+ release reactions. Reason: Consistent with direct rat evidence for ER membrane localisation. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-RNO-182097 | ACCEPT | Summary: Reactome places IP3R1 in the ER membrane in the IP3-mediated Ca2+ release reactions. Reason: Consistent with direct rat evidence for ER membrane localisation. Supporting Evidence: PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plasma membrane IP3R inferred by phylogeny. Reason: A minor plasma membrane pool of IP3Rs is reported in some cells, and PAINT placed the term at the family node; for IP3R1 most of the receptor is in the ER and the platelet data place type III, not type I, at the plasma membrane. Kept as a peripheral location. Supporting Evidence: PMID:19845505 but they are also expressed within the nuclear envelope [4], nucleoplasmic reticulum [5], Golgi apparatus [6], plasma membrane [7] PMID:10828023 the type I receptor involved with Ca(++) release from intracellular stores |
| GO:0005955 calcineurin complex | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Calcineurin complex membership transferred from mouse. Reason: IP3R1 co-precipitates with calcineurin (via FKBP12 or Bcl-2) but is a substrate/partner, not a subunit of the calcineurin heterodimer. The complex term overstates the relationship. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: MGI:MGI:96623 SUPPORTS SOURCE BUT NOT TARGET Co-precipitation with calcineurin does not make IP3R1 a calcineurin complex subunit. Supporting Evidence: PMID:15212990 we now show that calcineurin-IP3-R interactions are mediated by Bcl-2 in brain slices following short-term treatment with domoic acid |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Generic ion transport from InterPro. Reason: IP3R1 mediates Ca2+ release from the ER; refine to the specific transport process carried by the gene. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0006816 calcium ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Calcium ion transport; IP3R1 moves Ca2+ from the ER lumen into the cytosol. Reason: Correct but general; refine to release of sequestered Ca2+ into cytosol by the ER. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0006816 calcium ion transport | ISO GO_REF:0000121 | MODIFY | Summary: Calcium ion transport; IP3R1 moves Ca2+ from the ER lumen into the cytosol. Reason: Correct but general; refine to release of sequestered Ca2+ into cytosol by the ER. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96623 SUPPORTS TRANSFER Calcium ion transport is correct; refine to ER Ca2+ release. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IP3R1 is the effector of PLC-activating GPCR signalling, converting IP3 into Ca2+ release. Reason: IP3R1 performs the IP3-to-Ca2+ step of the PLC pathway; PAINT places the function on the IP3R family, and rat-cell data (mGluR, vasopressin, bradykinin responses) show IP3R1-dependent Ca2+ release downstream of these receptors. Supporting Evidence: UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) PMID:24814243 Expression of AdsiRNA-I in liver decreased peak Ca(2+) amplitude induced by vasopressin in isolated hepatocytes 2 days after HX. PMID:16223735 We demonstrated that overexpression of PC2, as well as type I IP3 receptor (IP3R), significantly prolonged the half-decay time (t1/2) of IP3-induced Ca2+ transients. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IDA PMID:16223735 Polycystin 2 interacts with type I inositol 1,4,5-trisphosph... | ACCEPT | Summary: IP3R1 mediates IP3-evoked Ca2+ release in the PLC signalling pathway. Reason: IP3R1 performs the IP3-to-Ca2+ step; IP3-evoked Ca2+ transients were modulated by IP3R1 and its partner polycystin-2. Supporting Evidence: PMID:16223735 We demonstrated that overexpression of PC2, as well as type I IP3 receptor (IP3R), significantly prolonged the half-decay time (t1/2) of IP3-induced Ca2+ transients. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 is the effector of PLC-activating GPCR signalling, converting IP3 into Ca2+ release. Reason: IP3R1 performs the IP3-to-Ca2+ step of the PLC pathway; PAINT places the function on the IP3R family, and rat-cell data (mGluR, vasopressin, bradykinin responses) show IP3R1-dependent Ca2+ release downstream of these receptors. Supporting Evidence: UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) PMID:24814243 Expression of AdsiRNA-I in liver decreased peak Ca(2+) amplitude induced by vasopressin in isolated hepatocytes 2 days after HX. PMID:16223735 We demonstrated that overexpression of PC2, as well as type I IP3 receptor (IP3R), significantly prolonged the half-decay time (t1/2) of IP3-induced Ca2+ transients. |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IMP PMID:15911880 Junctional membrane inositol 1,4,5-trisphosphate receptor co... | MODIFY | Summary: Positive regulation of cytosolic Ca2+; IP3R1 itself releases Ca2+ into the cytosol. Reason: Knockdown of IP3R1 reduces agonist-evoked Ca2+ rises, but IP3R1 is the transporter that raises cytosolic Ca2+, not a regulator of that process. The appropriate term is the transport process, which the gene already carries. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:24814243 Expression of AdsiRNA-I in liver decreased peak Ca(2+) amplitude induced by vasopressin in isolated hepatocytes 2 days after HX. PMID:15911880 it couples the plasmalemmal EGFR with IP(3)R1 at the Ca(2+) store located juxtaposed to the plasma membrane |
| GO:0007204 positive regulation of cytosolic calcium ion concentration | IMP PMID:24814243 Calcium signalling from the type I inositol 1,4,5-trisphosph... | MODIFY | Summary: Positive regulation of cytosolic Ca2+; IP3R1 itself releases Ca2+ into the cytosol. Reason: Knockdown of IP3R1 reduces agonist-evoked Ca2+ rises, but IP3R1 is the transporter that raises cytosolic Ca2+, not a regulator of that process. The appropriate term is the transport process, which the gene already carries. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:24814243 Expression of AdsiRNA-I in liver decreased peak Ca(2+) amplitude induced by vasopressin in isolated hepatocytes 2 days after HX. PMID:15911880 it couples the plasmalemmal EGFR with IP(3)R1 at the Ca(2+) store located juxtaposed to the plasma membrane |
| GO:0007207 phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 acts in muscarinic (PLC-activating) acetylcholine receptor signalling. Reason: A receptor-specific instance of the PLC-GPCR pathway in which IP3R1 performs the Ca2+ release step; kept as a context-specific, non-core annotation. Supporting Evidence: UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0007338 single fertilization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1-mediated Ca2+ oscillations drive egg activation at fertilization. Reason: Curated UniProt (by similarity to mouse) states IP3R1 tunes fertilization Ca2+ oscillations; the channel performs the Ca2+ release that activates the egg. Physiological context, non-core. Supporting Evidence: UniProtKB:P29994 Regulates fertilization and egg activation by tuning the frequency and amplitude of calcium oscillations |
| GO:0007338 single fertilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: IP3R1-mediated Ca2+ oscillations drive egg activation at fertilization. Reason: Curated UniProt (by similarity to mouse) states IP3R1 tunes fertilization Ca2+ oscillations; the channel performs the Ca2+ release that activates the egg. Physiological context, non-core. Supporting Evidence: UniProtKB:P29994 Regulates fertilization and egg activation by tuning the frequency and amplitude of calcium oscillations |
| GO:0009791 post-embryonic development | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Post-embryonic development from mouse Itpr1-null phenotypes. Reason: Mouse Itpr1 mutants die or are ataxic after birth; this is a pleiotropic phenotype downstream of Ca2+ signalling, too broad to describe the gene product role. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: MGI:MGI:96623 SUPPORTS SOURCE BUT NOT TARGET Organism-level developmental phenotype of the knockout. Supporting Evidence: UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0010976 positive regulation of neuron projection development | IMP PMID:21211516 Potentiation of NGF-induced neurite outgrowth in PC12 cells ... | KEEP AS NON CORE | Summary: Itpr1 knockdown blocked papaverine potentiation of NGF neurite outgrowth in PC12 cells. Reason: siRNA against itpr1 (and itpr3) and IP3R antagonists abolished the potentiation, showing IP3R-dependent Ca2+ release is required in this context. A downstream cellular outcome, non-core. Supporting Evidence: PMID:21211516 by reduced expression of IP(3) receptor gene (i.e., itpr1 and itpr3) by siRNA |
| GO:0014069 postsynaptic density | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Postsynaptic density location transferred from mouse. Reason: IP3R1 is abundant in the spine ER of Purkinje dendrites and co-purifies with synaptic fractions; strict PSD membership is less certain. Peripheral neuronal location. Supporting Evidence: PMID:12676536 We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes. PMID:1311032 Ca(2+)-ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. |
| GO:0015278 intracellularly gated calcium channel activity | ISO GO_REF:0000121 | MODIFY | Summary: Intracellularly gated calcium channel activity; IP3R1 is gated by IP3. Reason: Correct parent term; refine to the specific IP3-gated term with direct rat evidence. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96623 SUPPORTS TRANSFER Parent of the IP3-gated channel term. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0015278 intracellularly gated calcium channel activity | ISS GO_REF:0000024 | MODIFY | Summary: Intracellularly gated calcium channel activity; IP3R1 is gated by IP3. Reason: Correct parent term; refine to the specific IP3-gated term with direct rat evidence. Proposed replacements: inositol 1,4,5-trisphosphate-gated calcium channel activity Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0016020 membrane | IDA PMID:1311032 Ca2+ stores in Purkinje neurons: endoplasmic reticulum subco... | MODIFY | Summary: Membrane location from Purkinje-cell immunolocalisation. Reason: True but general; the study shows IP3R1 in the ER (including smooth ER) of Purkinje cells, so ER membrane is the informative term. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:1311032 Ca(2+)-ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Membrane location from Purkinje-cell immunolocalisation. Reason: True but general; the study shows IP3R1 in the ER (including smooth ER) of Purkinje cells, so ER membrane is the informative term. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:1311032 Ca(2+)-ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. PMID:10506212 the truncation mutants are properly targeted and oriented in the endoplasmic reticulum membrane |
| GO:0016358 dendrite development | IEP PMID:19236309 Ins(1,4,5)P3 receptor type 1 associates with AKAP9 (AKAP450 ... | MARK AS OVER ANNOTATED | Summary: Dendrite development by expression pattern (IEP). Reason: The paper describes association of IP3R1 with AKAP450/PKA in cerebellar granule cells; expression in developing neurons does not show that IP3R1 executes dendrite development. Supporting Evidence: PMID:19236309 InsP3R1 forms a complex with AKAP450 and PKAIIbeta, localized in the Golgi apparatus of cerebellar granule cells |
| GO:0016529 sarcoplasmic reticulum | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IP3R1 is present in sarcoplasmic reticulum of muscle cells. Reason: The SR is the muscle ER; IP3R1 is found there (e.g. smooth muscle), although in rat myotubes the type 2 receptor dominated the SR and type 1 the nuclear envelope. Kept as a tissue-specific location. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane PMID:12615969 IP(3)R1 was predominantly localized in the perinuclear region, whereas IP(3)R3 was homogeneously distributed over the cytoplasm. |
| GO:0016529 sarcoplasmic reticulum | IDA PMID:16014380 Nuclear inositol 1,4,5-trisphosphate receptors regulate loca... | KEEP AS NON CORE | Summary: IP3R localisation in muscle SR and nuclear envelope of rat myotubes. Reason: The rat myotube study localises IP3Rs to SR and nuclear envelope (type 1 mainly in the inner nuclear membrane). SR is the muscle ER; kept as a tissue-specific location, deferring to the curator who read the full text. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane |
| GO:0016529 sarcoplasmic reticulum | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IP3R1 is present in sarcoplasmic reticulum of muscle cells. Reason: The SR is the muscle ER; IP3R1 is found there (e.g. smooth muscle), although in rat myotubes the type 2 receptor dominated the SR and type 1 the nuclear envelope. Kept as a tissue-specific location. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane PMID:12615969 IP(3)R1 was predominantly localized in the perinuclear region, whereas IP(3)R3 was homogeneously distributed over the cytoplasm. |
| GO:0016529 sarcoplasmic reticulum | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 is present in sarcoplasmic reticulum of muscle cells. Reason: The SR is the muscle ER; IP3R1 is found there (e.g. smooth muscle), although in rat myotubes the type 2 receptor dominated the SR and type 1 the nuclear envelope. Kept as a tissue-specific location. Supporting Evidence: PMID:16014380 type-1 receptors preferentially localized in the inner nuclear membrane PMID:12615969 IP(3)R1 was predominantly localized in the perinuclear region, whereas IP(3)R3 was homogeneously distributed over the cytoplasm. |
| GO:0019722 calcium-mediated signaling | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IP3R1 generates Ca2+ signals that drive calcium-mediated signalling. Reason: The channel produces the Ca2+ signal; the downstream calcium-mediated signalling is executed by Ca2+ sensors. Non-core. Supporting Evidence: UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0019855 calcium channel inhibitor activity | ISO GO_REF:0000121 | REMOVE | Summary: Calcium channel inhibitor activity transferred from human ITPR1. Reason: The human source annotation rests on PMID:16793548, which shows that IRBIT (AHCYL1) inhibits the IP3R by competing with IP3. The inhibitor is IRBIT; IP3R1 is the channel being inhibited. The ISO transfer propagates an apparent gene mis-attribution. Propagation Review Root cause: SOURCE BAD Failure modes: SOURCE MISCITATION Sources checked: UniProtKB:Q14643 SOURCE BAD Human IDA from PMID:16793548 describes IRBIT inhibiting IP3R; inhibitor activity belongs to IRBIT (AHCYL1). Supporting Evidence: PMID:16793548 IRBIT suppresses the activation of IP3R by competing with IP3 |
| GO:0019903 protein phosphatase binding | IDA PMID:15212990 Domoic acid enhances Bcl-2-calcineurin-inositol-1,4,5-trisph... | KEEP AS NON CORE | Summary: IP3R1 associates with calcineurin (via Bcl-2) in rat brain slices. Reason: Co-immunoprecipitation in rat brain slices shows calcineurin-IP3R interactions mediated by Bcl-2; a regulatory interaction, non-core. Supporting Evidence: PMID:15212990 we now show that calcineurin-IP3-R interactions are mediated by Bcl-2 in brain slices following short-term treatment with domoic acid |
| GO:0019904 protein domain specific binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Protein domain specific binding transferred from mouse. Reason: IP3R1 binds partners through defined domains (e.g. its C-terminal tail binds 4.1N; its coupling domain binds syntaxin 1B). Kept as non-core. Supporting Evidence: PMID:12676536 We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes. PMID:21424589 We found that a SNARE-domain of Syx1B, one of the two Syx1 isoforms, directly interacted with the type1 IP(3)R (IP(3)R1) internal coupling domain |
| GO:0030425 dendrite | IDA PMID:17471556 Inositol 1,4,5 trisphosphate receptor and chromogranin B are... | KEEP AS NON CORE | Summary: IP3R1 is present in dendrites of rat hippocampal neurons. Reason: Immunohistochemistry of rat hippocampal slices; IP3R1 is in the dendritic ER. A neuronal compartment, peripheral to the core activity. Supporting Evidence: PMID:17471556 Immunohistochemistry experiments showed a prominent expression of InsP(3)R1 in the CA1 region of the hippocampus |
| GO:0030658 transport vesicle membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Transport/secretory vesicle membrane from UniProt subcellular location (by similarity). Reason: Secretory-vesicle localisation of IP3Rs is contentious and rests on a bovine study; no rat IP3R1 data support it. Supporting Evidence: PMID:19845505 and perhaps also in secretory vesicles [8], although the latter is contentious [9] file:rat/Itpr1/Itpr1-deep-research-manual.md Other membranes are reported but secretory-vesicle localisation is contentious |
| GO:0030667 secretory granule membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Secretory granule membrane inferred by phylogeny. Reason: Secretory-vesicle localisation of IP3Rs is contentious; the IBA rests on human/bovine reports and ER retention of IP3R1 is well documented. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001010185 SOURCE WEAK OR INFERRED Secretory-granule localisation of IP3Rs is contentious; IP3R1 is retained in the ER. Supporting Evidence: PMID:19845505 and perhaps also in secretory vesicles [8], although the latter is contentious [9] PMID:21550988 IP(3)R1 and IP(3)R3 were uniformly distributed within the membranes of the endoplasmic reticulum (ER), but the distribution of IP(3)R2 was punctate. file:rat/Itpr1/Itpr1-deep-research-manual.md Other membranes are reported but secretory-vesicle localisation is contentious |
| GO:0030868 smooth endoplasmic reticulum membrane | IDA PMID:1311032 Ca2+ stores in Purkinje neurons: endoplasmic reticulum subco... | ACCEPT | Summary: IP3R1 is in smooth ER membranes of Purkinje neurons. Reason: Immuno-EM in Purkinje cells shows IP3R distributed through the smooth ER, a specific ER sub-compartment where it releases Ca2+. Supporting Evidence: PMID:1311032 Ca(2+)-ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. |
| GO:0031088 platelet dense granule membrane | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: Platelet dense granule membrane transferred from human ITPR1. Reason: The cited human platelet study places type I IP3R in intracellular membranes for Ca2+ release from stores; a dense-granule location for IP3R1 is not established and conflicts with the contested vesicle localisation of IP3Rs. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:Q14643 SOURCE WEAK OR INFERRED Human platelet study places type I IP3R in intracellular store membranes; dense-granule location not supported by the abstract. Supporting Evidence: PMID:10828023 the type I receptor involved with Ca(++) release from intracellular stores PMID:19845505 and perhaps also in secretory vesicles [8], although the latter is contentious [9] file:rat/Itpr1/Itpr1-deep-research-manual.md Other membranes are reported but secretory-vesicle localisation is contentious |
| GO:0031094 platelet dense tubular network | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Platelet dense tubular network (platelet ER) transferred from human. Reason: The dense tubular system is the platelet ER Ca2+ store; type I IP3R mediates Ca2+ release from intracellular stores in platelets. Cell-type-specific location. Supporting Evidence: PMID:10828023 the type I receptor involved with Ca(++) release from intracellular stores |
| GO:0032469 endoplasmic reticulum calcium ion homeostasis | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ER calcium ion homeostasis. Reason: IP3R1 is the main Ca2+ leak/release path from the ER and its turnover (e.g. Herp-mediated) tunes ER Ca2+ content; non-core. Supporting Evidence: PMID:22045699 Herp plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca(2+) release channels UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0032991 protein-containing complex | IDA PMID:12676536 Association of the type 1 inositol (1,4,5)-trisphosphate rec... | KEEP AS NON CORE | Summary: IP3R1 is part of a complex with 4.1N in rat brain synaptosomes. Reason: Co-immunoprecipitation of the 4.1N-IP3R1 complex from rat synaptosomes; no more specific complex term exists for this assembly. Supporting Evidence: PMID:12676536 We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 is part of a complex with 4.1N in rat brain synaptosomes. Reason: Co-immunoprecipitation of the 4.1N-IP3R1 complex from rat synaptosomes; no more specific complex term exists for this assembly. Supporting Evidence: PMID:12676536 We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes. |
| GO:0035091 phosphatidylinositol binding | IBA GO_REF:0000033 | MODIFY | Summary: Phosphatidylinositol binding; IP3R1 binds the soluble headgroup IP3, not a phosphatidylinositol lipid. Reason: GO:0035091 denotes binding of inositol-containing glycerophospholipids. The ligand of IP3R1 is the soluble second messenger IP3, captured by GO:0070679, which the gene carries with direct structural evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001010185 SUPPORTS SOURCE BUT NOT TARGET IP3 is a soluble inositol phosphate; phosphatidylinositol binding misdescribes the ligand. Proposed replacements: inositol 1,4,5 trisphosphate binding Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. |
| GO:0035091 phosphatidylinositol binding | ISO GO_REF:0000121 | MODIFY | Summary: Phosphatidylinositol binding; IP3R1 binds the soluble headgroup IP3, not a phosphatidylinositol lipid. Reason: GO:0035091 denotes binding of inositol-containing glycerophospholipids. The ligand of IP3R1 is the soluble second messenger IP3, captured by GO:0070679, which the gene carries with direct structural evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96623 SUPPORTS SOURCE BUT NOT TARGET IP3 is a soluble inositol phosphate; phosphatidylinositol binding misdescribes the ligand. Proposed replacements: inositol 1,4,5 trisphosphate binding Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. |
| GO:0035091 phosphatidylinositol binding | ISS GO_REF:0000024 | MODIFY | Summary: Phosphatidylinositol binding; IP3R1 binds the soluble headgroup IP3, not a phosphatidylinositol lipid. Reason: GO:0035091 denotes binding of inositol-containing glycerophospholipids. The ligand of IP3R1 is the soluble second messenger IP3, captured by GO:0070679, which the gene carries with direct structural evidence. Proposed replacements: inositol 1,4,5 trisphosphate binding Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. |
| GO:0036398 TCR signalosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 recruited to the TCR signalosome by Tespa1 (transferred from human). Reason: Tespa1 directly binds IP3R1 and recruits it to the TCR complex in T cells; a context-specific location, non-core. Supporting Evidence: PMID:28598420 Upon TCR stimulation, Tespa1 directly interacts with IP3R1 and recruits it to the TCR complex |
| GO:0036444 calcium import into the mitochondrion | IMP PMID:17178908 Chaperone-mediated coupling of endoplasmic reticulum and mit... | KEEP AS NON CORE | Summary: IP3R1 supplies Ca2+ for mitochondrial uptake at ER-mitochondria contacts. Reason: IP3R is coupled to VDAC1 via GRP75 and IP3R-mediated release enhances mitochondrial Ca2+ accumulation; the channel releases the Ca2+ taken up by the mitochondrial machinery. Kept as non-core. Supporting Evidence: PMID:17178908 We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca(2+)-release channel inositol 1,4,5-trisphosphate receptor (IP(3)R) through the molecular chaperone glucose-regulated protein 75 (grp75). PMID:17178908 Organellar Ca2+ measurements, using targeted recombinant Ca2+ probes, confirmed functional interaction between the IP3R and the mitochondrial Ca2+ uptake machinery, which was abolished by grp75 knockdown. |
| GO:0042045 epithelial fluid transport | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Epithelial fluid transport transferred from mouse. Reason: Curated UniProt (by similarity) links IP3R1 to epithelial electrolyte and fluid secretion via AHCYL1; the channel provides the Ca2+ signal. Physiological, non-core. Supporting Evidence: UniProtKB:P29994 Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 |
| GO:0042802 identical protein binding | IPI PMID:23479737 Fragmented inositol 1,4,5-trisphosphate receptors retain tet... | KEEP AS NON CORE | Summary: IP3R1 subunits/fragments self-associate into tetramers. Reason: Co-expressed IP3R1 fragments physically associate and form functional channels; self-association reflects tetramer assembly. Structural, non-core. Supporting Evidence: PMID:23479737 when recombinant IP3R1 fragments, corresponding to those predicted to be generated by caspase or calpain cleavage, are stably coexpressed in cells, they physically associate and form functional channels UniProtKB:P29994 Homotetramer (PubMed:10506212, PubMed:36376291) |
| GO:0042803 protein homodimerization activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Protein homodimerization activity transferred from mouse. Reason: UniProt records homodimer reports, but the functional unit is the tetramer; kept as non-core structural property. Supporting Evidence: UniProtKB:P29994 Homodimer (PubMed:21892169, PubMed:22286060) UniProtKB:P29994 Homotetramer (PubMed:10506212, PubMed:36376291) |
| GO:0043005 neuron projection | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Neuron projection location from ARBA. Reason: Consistent with dendritic IP3R1 in rat hippocampal neurons; non-core neuronal compartment. Supporting Evidence: PMID:17471556 Immunohistochemistry experiments showed a prominent expression of InsP(3)R1 in the CA1 region of the hippocampus |
| GO:0043025 neuronal cell body | IDA PMID:17471556 Inositol 1,4,5 trisphosphate receptor and chromogranin B are... | KEEP AS NON CORE | Summary: IP3R1 is present in neuronal cell bodies of rat hippocampus. Reason: Immunohistochemistry in rat hippocampal slices; non-core neuronal compartment. Supporting Evidence: PMID:17471556 Immunohistochemistry experiments showed a prominent expression of InsP(3)R1 in the CA1 region of the hippocampus |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:28072885 Functional Role of Intracellular Calcium Receptor Inositol 1... | KEEP AS NON CORE | Summary: IP3R1 activity promotes neuronal death after neonatal anoxia. Reason: IP3R block with 2-APB reduced neuronal death after anoxia; Ca2+ released by IP3R1 contributes to cell death. Context-dependent, non-core (2-APB is non-specific). Supporting Evidence: PMID:28072885 Intrahippocampal injection of non-specific IP3R1 blocker 2-APB clearly reduced the number of Fluoro-Jade C and Tunel positive cells UniProtKB:P29994 Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CAMK2 complex |
| GO:0043065 positive regulation of apoptotic process | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Positive regulation of apoptosis transferred from mouse. Reason: IP3R1-released Ca2+ promotes apoptosis in several contexts (by similarity); non-core. Supporting Evidence: UniProtKB:P29994 Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CAMK2 complex |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:20434434 Enhanced hypoxic preconditioning by isoflurane: signaling ge... | KEEP AS NON CORE | Summary: IP3R silencing prevented preconditioning-induced neuroprotection. Reason: RNA silencing of IP3 receptors (about 90% loss of ITPR1 mRNA) abolished preconditioning neuroprotection in rat hippocampal slices; the anti-apoptotic effect is an indirect, context-specific consequence of IP3R1 Ca2+ signalling. Non-core, opposite in sign to the anoxia row because the contexts differ. Supporting Evidence: PMID:20434434 Intracellular Ca(2+) chelation and RNA silencing of IP(3) receptors prevented preconditioning neuroprotection and gene responses. |
| GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site | IDA PMID:17178908 Chaperone-mediated coupling of endoplasmic reticulum and mit... | KEEP AS NON CORE | Summary: IP3R is located at mitochondria-associated ER membranes. Reason: IP3R is enriched in the MAM fraction in complex with GRP75 and VDAC1; a functional sub-domain of the ER membrane. Supporting Evidence: PMID:17178908 We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca(2+)-release channel inositol 1,4,5-trisphosphate receptor (IP(3)R) through the molecular chaperone glucose-regulated protein 75 (grp75). |
| GO:0044325 transmembrane transporter binding | IPI PMID:23982204 Activation of the Cl- channel ANO1 by localized calcium sign... | KEEP AS NON CORE | Summary: IP3R1 binds the Ca2+-activated Cl- channel ANO1 in rat DRG neurons. Reason: Co-immunoprecipitation from rat DRG and GST pull-downs show ANO1 binding to IP3R1, tethering ER-PM junctions; a scaffolding interaction, non-core. Supporting Evidence: PMID:23982204 Interaction of the carboxyl terminus and the first intracellular loop of ANO1 with IP3R1 (inositol 1,4,5-trisphosphate receptor 1) contributed to the tethering. |
| GO:0044877 protein-containing complex binding | IDA PMID:15212990 Domoic acid enhances Bcl-2-calcineurin-inositol-1,4,5-trisph... | KEEP AS NON CORE | Summary: IP3R1 binds the calcineurin-Bcl-2 complex in rat brain. Reason: Calcineurin-IP3R interactions mediated by Bcl-2 in rat brain slices; regulatory, non-core. Supporting Evidence: PMID:15212990 we now show that calcineurin-IP3-R interactions are mediated by Bcl-2 in brain slices following short-term treatment with domoic acid |
| GO:0045202 synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 acts at synapses. Reason: IP3R1 is enriched at synaptic locations and in spine ER of neurons; neuronal location, non-core. Supporting Evidence: PMID:12676536 We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:12615969 Microtubule-dependent redistribution of the type-1 inositol ... | KEEP AS NON CORE | Summary: IP3R1 is concentrated in the perinuclear ER of A7r5 smooth muscle cells. Reason: Direct immunolocalisation in rat A7r5 cells; reflects ER distribution, non-core. Supporting Evidence: PMID:12615969 IP(3)R1 was predominantly localized in the perinuclear region, whereas IP(3)R3 was homogeneously distributed over the cytoplasm. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IP3R1 is concentrated in the perinuclear ER of A7r5 smooth muscle cells. Reason: Direct immunolocalisation in rat A7r5 cells; reflects ER distribution, non-core. Supporting Evidence: PMID:12615969 IP(3)R1 was predominantly localized in the perinuclear region, whereas IP(3)R3 was homogeneously distributed over the cytoplasm. |
| GO:0050848 regulation of calcium-mediated signaling | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 regulates TCR-induced Ca2+ signalling (transferred from human). Reason: Tespa1-recruited IP3R1 is required for optimal TCR-induced Ca2+ flux; IP3R1 generates the Ca2+ signal. Non-core. Supporting Evidence: PMID:28598420 Upon TCR stimulation, Tespa1 directly interacts with IP3R1 and recruits it to the TCR complex |
| GO:0050849 negative regulation of calcium-mediated signaling | ISO GO_REF:0000121 | REMOVE | Summary: Negative regulation of calcium-mediated signaling transferred from human ITPR1. Reason: The human source is PMID:16793548, which shows IRBIT inhibiting the IP3R. IP3R1 is the target of that inhibition, not a negative regulator of Ca2+ signalling; the source row appears mis-attributed and the ISO propagates it. Propagation Review Root cause: SOURCE BAD Failure modes: SOURCE MISCITATION REGULATORY SIGN INVERSION Sources checked: UniProtKB:Q14643 SOURCE BAD Human IDA from PMID:16793548 describes IRBIT inhibiting IP3R; the negative regulator is IRBIT. Supporting Evidence: PMID:16793548 IRBIT suppresses the activation of IP3R by competing with IP3 |
| GO:0050882 voluntary musculoskeletal movement | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Voluntary movement from the ataxic phenotype of mouse Itpr1 mutants. Reason: Loss of IP3R1 causes ataxia in mice (and spinocerebellar ataxia in humans) through loss of Purkinje-cell Ca2+ signalling; organism-level phenotype, non-core. Supporting Evidence: UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0051209 release of sequestered calcium ion into cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IP3R1 releases sequestered Ca2+ from the ER into the cytosol. Reason: This is the process executed by the core channel activity; supported by direct rat channel recordings and structural data. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0051209 release of sequestered calcium ion into cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: IP3R1 releases sequestered Ca2+ from the ER into the cytosol. Reason: This is the process executed by the core channel activity; supported by direct rat channel recordings and structural data. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0051209 release of sequestered calcium ion into cytosol | IMP PMID:16223735 Polycystin 2 interacts with type I inositol 1,4,5-trisphosph... | ACCEPT | Summary: IP3R1 overexpression prolongs IP3-induced Ca2+ release transients. Reason: Overexpressing type I IP3R in oocytes altered IP3-induced Ca2+ release kinetics, consistent with IP3R1 mediating the release. Supporting Evidence: PMID:16223735 We demonstrated that overexpression of PC2, as well as type I IP3 receptor (IP3R), significantly prolonged the half-decay time (t1/2) of IP3-induced Ca2+ transients. PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers |
| GO:0051209 release of sequestered calcium ion into cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 releases sequestered Ca2+ from the ER into the cytosol. Reason: This is the process executed by the core channel activity; supported by direct rat channel recordings and structural data. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0051209 release of sequestered calcium ion into cytosol | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 releases sequestered Ca2+ from the ER into the cytosol. Reason: This is the process executed by the core channel activity; supported by direct rat channel recordings and structural data. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0051289 protein homotetramerization | IDA PMID:36376291 Conformational motions and ligand-binding underlying gating ... | KEEP AS NON CORE | Summary: IP3R1 assembles as a homotetramer. Reason: Tetramer assembly is required to form the channel pore (cryo-EM, oligomerization studies); structural prerequisite rather than a biological role. Non-core. Supporting Evidence: PMID:36376291 All IP3R channels are tetrameric assemblies of monomers of either identical or different subtypes UniProtKB:P29994 Homotetramer (PubMed:10506212, PubMed:36376291) |
| GO:0051289 protein homotetramerization | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 assembles as a homotetramer. Reason: Tetramer assembly is required to form the channel pore (cryo-EM, oligomerization studies); structural prerequisite rather than a biological role. Non-core. Supporting Evidence: PMID:36376291 All IP3R channels are tetrameric assemblies of monomers of either identical or different subtypes UniProtKB:P29994 Homotetramer (PubMed:10506212, PubMed:36376291) |
| GO:0051289 protein homotetramerization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: IP3R1 assembles as a homotetramer. Reason: Tetramer assembly is required to form the channel pore (cryo-EM, oligomerization studies); structural prerequisite rather than a biological role. Non-core. Supporting Evidence: PMID:36376291 All IP3R channels are tetrameric assemblies of monomers of either identical or different subtypes UniProtKB:P29994 Homotetramer (PubMed:10506212, PubMed:36376291) |
| GO:0051480 regulation of cytosolic calcium ion concentration | ISO GO_REF:0000121 | MODIFY | Summary: Regulation of cytosolic Ca2+ concentration. Reason: IP3R1 directly moves Ca2+ into the cytosol; the specific transport process is the better description. Propagation Review Root cause: NO FAILURE CORE Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:96623 SUPPORTS TRANSFER IP3R1 is the transporter; transport term is more precise. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0051480 regulation of cytosolic calcium ion concentration | ISS GO_REF:0000024 | MODIFY | Summary: Regulation of cytosolic Ca2+ concentration. Reason: IP3R1 directly moves Ca2+ into the cytosol; the specific transport process is the better description. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0051928 positive regulation of calcium ion transport | IDA PMID:19036964 Deranged calcium signaling and neurodegeneration in spinocer... | MODIFY | Summary: Positive regulation of calcium ion transport, from ataxin-3 sensitisation of IP3R1. Reason: In this study mutant ataxin-3 sensitised IP3R1; IP3R1 itself is the Ca2+-transporting channel, so the regulation term belongs to ataxin-3. For IP3R1 the appropriate process is Ca2+ release by the ER. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:19036964 InsP(3)R1 was sensitized to activation by InsP(3) in the presence of mutant ATX3(exp) |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Generic transmembrane transport from InterPro. Reason: Refine to the specific Ca2+ release process. Proposed replacements: release of sequestered calcium ion into cytosol by endoplasmic reticulum Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ER-stress-induced intrinsic apoptosis. Reason: IP3R1-mediated Ca2+ transfer from ER to mitochondria promotes ER-stress apoptosis (by similarity); context-specific, non-core. Supporting Evidence: UniProtKB:P29994 Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CAMK2 complex PMID:17178908 Organellar Ca2+ measurements, using targeted recombinant Ca2+ probes, confirmed functional interaction between the IP3R and the mitochondrial Ca2+ uptake machinery, which was abolished by grp75 knockdown. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ER-stress-induced intrinsic apoptosis. Reason: IP3R1-mediated Ca2+ transfer from ER to mitochondria promotes ER-stress apoptosis (by similarity); context-specific, non-core. Supporting Evidence: UniProtKB:P29994 Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CAMK2 complex PMID:17178908 Organellar Ca2+ measurements, using targeted recombinant Ca2+ probes, confirmed functional interaction between the IP3R and the mitochondrial Ca2+ uptake machinery, which was abolished by grp75 knockdown. |
| GO:0070588 calcium ion transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Calcium ion transmembrane transport. Reason: IP3R1 transports Ca2+ across the ER membrane; accepted as the transport term (refined by GO:1903514). Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0070679 inositol 1,4,5 trisphosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: IP3R1 binds IP3, its activating ligand. Reason: The IP3-binding pocket of rat IP3R1 is resolved by cryo-EM and the rat receptor has an apparent IP3 affinity of about 0.27 microM; IP3 binding is intrinsic to the core gating mechanism. Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0070679 inositol 1,4,5 trisphosphate binding | IDA PMID:36376291 Conformational motions and ligand-binding underlying gating ... | ACCEPT | Summary: IP3R1 binds IP3, its activating ligand. Reason: The IP3-binding pocket of rat IP3R1 is resolved by cryo-EM and the rat receptor has an apparent IP3 affinity of about 0.27 microM; IP3 binding is intrinsic to the core gating mechanism. Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0070679 inositol 1,4,5 trisphosphate binding | IEA GO_REF:0000120 | ACCEPT | Summary: IP3R1 binds IP3, its activating ligand. Reason: The IP3-binding pocket of rat IP3R1 is resolved by cryo-EM and the rat receptor has an apparent IP3 affinity of about 0.27 microM; IP3 binding is intrinsic to the core gating mechanism. Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0070679 inositol 1,4,5 trisphosphate binding | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R1 binds IP3, its activating ligand. Reason: The IP3-binding pocket of rat IP3R1 is resolved by cryo-EM and the rat receptor has an apparent IP3 affinity of about 0.27 microM; IP3 binding is intrinsic to the core gating mechanism. Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0070679 inositol 1,4,5 trisphosphate binding | ISS GO_REF:0000024 | ACCEPT | Summary: IP3R1 binds IP3, its activating ligand. Reason: The IP3-binding pocket of rat IP3R1 is resolved by cryo-EM and the rat receptor has an apparent IP3 affinity of about 0.27 microM; IP3 binding is intrinsic to the core gating mechanism. Supporting Evidence: PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| 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 directly sensitises IP3R1 to IP3. Reason: In DT40 cells expressing single rat IP3R subtypes, cAMP sensitised all IP3R subtypes to IP3 independent of PKA. A regulatory response of the channel, non-core. Supporting Evidence: PMID:20189985 These results establish that cAMP itself increases the sensitivity of all IP(3)R subtypes to IP(3). |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Cellular response to hypoxia. Reason: Supported only by hypoxia-induced changes in IP3R1 expression; expression changes do not show IP3R1 executes a hypoxia response. Supporting Evidence: PMID:17285299 gene expression of types 1 and 2 IP(3) receptors is significantly increased after the exposure of mice to hypoxic stimulus for 6 h and also in rat cerebellar granular cells |
| GO:0071456 cellular response to hypoxia | IEP PMID:17285299 Hypoxia modulates gene expression of IP3 receptors in rodent... | MARK AS OVER ANNOTATED | Summary: Cellular response to hypoxia. Reason: Supported only by hypoxia-induced changes in IP3R1 expression; expression changes do not show IP3R1 executes a hypoxia response. Supporting Evidence: PMID:17285299 gene expression of types 1 and 2 IP(3) receptors is significantly increased after the exposure of mice to hypoxic stimulus for 6 h and also in rat cerebellar granular cells |
| GO:0097060 synaptic membrane | IDA PMID:12676536 Association of the type 1 inositol (1,4,5)-trisphosphate rec... | KEEP AS NON CORE | Summary: IP3R1 is enriched in synaptic membrane fractions. Reason: IP3R1 is enriched at synaptic locations and co-immunoprecipitates with 4.1N from rat synaptosomes; non-core neuronal location. Supporting Evidence: PMID:12676536 We showed that both 4.1N and InsP(3)R1 were enriched in synaptic locations and immunoprecipitated the 4.1N-InsP(3)R1 complex from rat brain synaptosomes. |
| GO:0097421 liver regeneration | IMP PMID:24814243 Calcium signalling from the type I inositol 1,4,5-trisphosph... | KEEP AS NON CORE | Summary: IP3R1-dependent Ca2+ signalling is required early in rat liver regeneration. Reason: Adenoviral siRNA knockdown of IP3R1 delayed liver regeneration after partial hepatectomy; physiological, non-core. Supporting Evidence: PMID:24814243 InsP3 R-I-dependent Ca(2+) signalling is an early triggering pathway required for liver regeneration. |
| GO:0098685 Schaffer collateral - CA1 synapse | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: IP3R1 at Schaffer collateral-CA1 synapses (from mouse). Reason: IP3R1 is prominent in CA1 neurons; synapse-specific location, non-core. Supporting Evidence: PMID:17471556 Immunohistochemistry experiments showed a prominent expression of InsP(3)R1 in the CA1 region of the hippocampus |
| GO:0098695 inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels | ISO GO_REF:0000121 | ACCEPT | Summary: IP3R activity regulating postsynaptic cytosolic Ca2+. Reason: A neuron-specific descendant of the core IP3-gated channel activity; IP3R1 is the main neuronal subtype and releases Ca2+ in dendrites and spines. Supporting Evidence: PMID:17471556 Immunohistochemistry experiments showed a prominent expression of InsP(3)R1 in the CA1 region of the hippocampus UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:0098793 presynapse | IDA PMID:1311032 Ca2+ stores in Purkinje neurons: endoplasmic reticulum subco... | KEEP AS NON CORE | Summary: IP3R1 is present in presynaptic compartments of Purkinje neurons. Reason: Immuno-EM of Purkinje cells shows IP3R in ER throughout the neuron, including axonal regions; non-core. Supporting Evidence: PMID:1311032 Ca(2+)-ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. |
| GO:0098794 postsynapse | IDA PMID:1311032 Ca2+ stores in Purkinje neurons: endoplasmic reticulum subco... | KEEP AS NON CORE | Summary: IP3R1 is present in presynaptic compartments of Purkinje neurons. Reason: Immuno-EM of Purkinje cells shows IP3R in ER throughout the neuron, including axonal regions; non-core. Supporting Evidence: PMID:1311032 Ca(2+)-ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. |
| GO:0098982 GABA-ergic synapse | IDA PMID:1311032 Ca2+ stores in Purkinje neurons: endoplasmic reticulum subco... | KEEP AS NON CORE | Summary: IP3R1 is present in presynaptic compartments of Purkinje neurons. Reason: Immuno-EM of Purkinje cells shows IP3R in ER throughout the neuron, including axonal regions; non-core. Supporting Evidence: PMID:1311032 Ca(2+)-ATPase and the InsP3 receptor have a widespread, although not identical, distribution throughout the ER. |
| GO:0099566 regulation of postsynaptic cytosolic calcium ion concentration | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Regulation of postsynaptic cytosolic Ca2+ concentration. Reason: Follows from the postsynaptic IP3R channel activity; non-core neuronal process. Supporting Evidence: PMID:17471556 Immunohistochemistry experiments showed a prominent expression of InsP(3)R1 in the CA1 region of the hippocampus UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:1903514 release of sequestered calcium ion into cytosol by endoplasmic reticulum | ISO GO_REF:0000121 | ACCEPT | Summary: Release of sequestered Ca2+ into the cytosol by the ER. Reason: The precise process executed by IP3R1 channel activity. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:1903514 release of sequestered calcium ion into cytosol by endoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: Release of sequestered Ca2+ into the cytosol by the ER. Reason: The precise process executed by IP3R1 channel activity. Supporting Evidence: PMID:15533917 we compared single-channel behavior of the recombinant rat InsP3R1, InsP3R2, and InsP3R3 expressed in Sf9 cells, reconstituted into planar lipid bilayers PMID:22547632 we examined the effects of [ATP] on the Ca2+ dependency of rat InsP3R-1 (rInsP3R-1) and mouse InsP3R-2 (mInsP3R-2) activity expressed in DT40-3KO cells PMID:36376291 These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP, revealing conformational changes that couple ligand-binding to channel opening. UniProtKB:P29994 Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER) |
| GO:2000347 positive regulation of hepatocyte proliferation | IMP PMID:24814243 Calcium signalling from the type I inositol 1,4,5-trisphosph... | KEEP AS NON CORE | Summary: IP3R1 knockdown reduced hepatocyte proliferation in regenerating rat liver. Reason: PCNA staining showed reduced hepatocyte proliferation after IP3R1 knockdown; downstream physiological role, non-core. Supporting Evidence: PMID:24814243 reduced hepatocyte proliferation, as evaluated by PCNA staining |
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Download this section (compressed HTML)Q: Human ITPR1 carries IDA annotations to calcium channel inhibitor activity and negative regulation of calcium-mediated signaling from PMID:16793548, a paper showing IRBIT (AHCYL1) inhibits IP3R. Should these be moved to AHCYL1, which would also remove the rat ISO rows?
Q: Does a functional plasma-membrane pool of IP3R1 (as opposed to IP3R3) exist in native rat cells, or is the plasma membrane IBA driven by other subtypes?
Q: Is the rat myotube sarcoplasmic reticulum IDA (PMID:16014380) attributable to IP3R1, given that the abstract places type 2 in the SR and type 1 in the inner nuclear membrane?
Experiment: Express IP3R1 restricted to the inner nuclear membrane (or ER-only) in IP3R-null cells and compare nucleoplasmic versus cytosolic Ca2+ and CREB phosphorylation after targeted IP3 uncaging.
Hypothesis: Nuclear-envelope IP3R1 generates nucleoplasmic Ca2+ transients independently of cytosolic release and drives CREB phosphorylation.
Type: targeted expression with organelle Ca2+ imaging
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