Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0048066 developmental pigmentation	IBA GO_REF:0000033	REMOVE	Summary: developmental pigmentation is not supported as an appropriate annotation for Ednra after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Ednra biology. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0086100 endothelin receptor signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: endothelin receptor signaling pathway is biologically consistent with the curated synthesis for Ednra and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling." file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes EDNRA as transducing endothelin signals through heterotrimeric G proteins, especially Gq/11-calcium and ERK signaling.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Ednra and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA as a 7-transmembrane class A GPCR functioning at the plasma membrane of target cells.
GO:0004962 endothelin receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: endothelin receptor activity is biologically consistent with the curated synthesis for Ednra and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA/ETA as an endothelin peptide receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the canonical receptor state.
GO:0042310 vasoconstriction	IBA GO_REF:0000033	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Ednra and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes ETA/EDNRA as the principal receptor mediating ET-1-driven vascular smooth muscle vasoconstriction.
GO:0004930 G protein-coupled receptor activity	IEA GO_REF:0000120	MODIFY	Summary: G protein-coupled receptor activity captures the right general biology for Ednra, but a more specific GO term is available. Reason: The current term is too broad or less precise than endothelin receptor activity for this gene. Replace with endothelin receptor activity to align the annotation with the reviewed evidence. Proposed replacements: endothelin receptor activity Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor.
GO:0004962 endothelin receptor activity	IEA GO_REF:0000120	ACCEPT	Summary: endothelin receptor activity is biologically consistent with the curated synthesis for Ednra and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA/ETA as an endothelin peptide receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the canonical receptor state.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Ednra and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA as a 7-transmembrane class A GPCR functioning at the plasma membrane of target cells.
GO:0007165 signal transduction	IEA GO_REF:0000043	MODIFY	Summary: signal transduction captures the right general biology for Ednra, but a more specific GO term is available. Reason: The current term is too broad or less precise than endothelin receptor signaling pathway for this gene. Replace with endothelin receptor signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: endothelin receptor signaling pathway Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000120	MODIFY	Summary: G protein-coupled receptor signaling pathway captures the right general biology for Ednra, but a more specific GO term is available. Reason: The current term is too broad or less precise than endothelin receptor signaling pathway for this gene. Replace with endothelin receptor signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: endothelin receptor signaling pathway Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0008015 blood circulation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: blood circulation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0008217 regulation of blood pressure	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: membrane is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor.
GO:0030202 heparin proteoglycan metabolic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: heparin proteoglycan metabolic process is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0042310 vasoconstriction	IEA GO_REF:0000120	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Ednra and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes ETA/EDNRA as the principal receptor mediating ET-1-driven vascular smooth muscle vasoconstriction.
GO:0043123 positive regulation of canonical NF-kappaB signal transduction	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: positive regulation of canonical NF-kappaB signal transduction is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0048484 enteric nervous system development	IEA GO_REF:0000002	REMOVE	Summary: enteric nervous system development is not supported as an appropriate annotation for Ednra after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Ednra biology. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0055078 sodium ion homeostasis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: sodium ion homeostasis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0061028 establishment of endothelial barrier	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: establishment of endothelial barrier is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0070294 renal sodium ion absorption	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: renal sodium ion absorption is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0071806 protein transmembrane transport	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: protein transmembrane transport is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0072112 podocyte differentiation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: podocyte differentiation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0097018 renal albumin absorption	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: renal albumin absorption is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0006874 intracellular calcium ion homeostasis	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: intracellular calcium ion homeostasis is too broad relative to the more specific EDNRA calcium-signaling annotations retained elsewhere. Reason: EDNRA-dependent PLC/calcium signaling is better captured by the specific cytosolic-calcium and podocyte calcium annotations than by this broad homeostasis term. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling."
GO:0014824 artery smooth muscle contraction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: artery smooth muscle contraction is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0141156 cAMP/PKA signal transduction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cAMP/PKA signal transduction is supported in a DRG pain-sensitization context but is not the core EDNRA receptor function. Reason: PMID:30990108 supports ETAR-PKA-mediated TRPA1 sensitization; this is a context-specific nociceptive signaling branch rather than the central endothelin receptor/PLC/calcium pathway. Supporting Evidence: PMID:30990108 ET-1-induced sensitization of TRPA1 in vitro requires ETAR-mediated PKA signaling pathway.
GO:0005886 plasma membrane	ISO GO_REF:0000119	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Ednra and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA as a 7-transmembrane class A GPCR functioning at the plasma membrane of target cells.
GO:0001934 positive regulation of protein phosphorylation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of protein phosphorylation is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0001821 histamine secretion	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: histamine secretion is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0003094 glomerular filtration	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: glomerular filtration is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0004962 endothelin receptor activity	ISO GO_REF:0000096	ACCEPT	Summary: endothelin receptor activity is biologically consistent with the curated synthesis for Ednra and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA/ETA as an endothelin peptide receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the canonical receptor state.
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway	ISO GO_REF:0000096	ACCEPT	Summary: phospholipase C-activating G protein-coupled receptor signaling pathway is a specific supported branch of EDNRA signaling. Reason: EDNRA is an endothelin GPCR whose reviewed evidence explicitly supports Gq/G11-dependent PLC/phosphatidylinositol-calcium signaling, so this mechanistic pathway term should be retained. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling."
GO:0007204 positive regulation of cytosolic calcium ion concentration	ISO GO_REF:0000096	ACCEPT	Summary: positive regulation of cytosolic calcium ion concentration is biologically consistent with the curated synthesis for Ednra and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling." file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon reports that EDNRA Gq/11 coupling increases intracellular calcium and activates ERK phosphorylation.
GO:0007266 Rho protein signal transduction	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: Rho protein signal transduction is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0008284 positive regulation of cell population proliferation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of cell population proliferation is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0014824 artery smooth muscle contraction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: artery smooth muscle contraction is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0030315 T-tubule	ISO GO_REF:0000096	REMOVE	Summary: T-tubule is not supported as an appropriate annotation for Ednra after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Ednra biology. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0031965 nuclear membrane	ISO GO_REF:0000096	REMOVE	Summary: nuclear membrane is not supported as an appropriate annotation for Ednra after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Ednra biology. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0032496 response to lipopolysaccharide	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: response to lipopolysaccharide is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0042310 vasoconstriction	ISO GO_REF:0000096	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Ednra and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes ETA/EDNRA as the principal receptor mediating ET-1-driven vascular smooth muscle vasoconstriction.
GO:0042310 vasoconstriction	ISO GO_REF:0000119	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Ednra and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes ETA/EDNRA as the principal receptor mediating ET-1-driven vascular smooth muscle vasoconstriction.
GO:0042482 positive regulation of odontogenesis	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of odontogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0043066 negative regulation of apoptotic process	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: negative regulation of apoptotic process is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0048144 fibroblast proliferation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: fibroblast proliferation is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0048659 smooth muscle cell proliferation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: smooth muscle cell proliferation is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0050678 regulation of epithelial cell proliferation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: regulation of epithelial cell proliferation is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0051281 positive regulation of release of sequestered calcium ion into cytosol	ISO GO_REF:0000096	ACCEPT	Summary: positive regulation of release of sequestered calcium ion into cytosol is biologically consistent with the curated synthesis for Ednra and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling."
GO:0051928 positive regulation of calcium ion transport	ISO GO_REF:0000096	ACCEPT	Summary: positive regulation of calcium ion transport is biologically consistent with the curated synthesis for Ednra and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling."
GO:0070374 positive regulation of ERK1 and ERK2 cascade	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of ERK1 and ERK2 cascade is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0071260 cellular response to mechanical stimulus	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: cellular response to mechanical stimulus is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0090023 positive regulation of neutrophil chemotaxis	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of neutrophil chemotaxis is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0090184 positive regulation of kidney development	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of kidney development is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0004962 endothelin receptor activity	IMP PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	ACCEPT	Summary: endothelin receptor activity is biologically consistent with the curated synthesis for Ednra and is supported by IMP evidence (PMID:24722437). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA/ETA as an endothelin peptide receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the canonical receptor state.
GO:0086100 endothelin receptor signaling pathway	IMP PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	ACCEPT	Summary: endothelin receptor signaling pathway is biologically consistent with the curated synthesis for Ednra and is supported by IMP evidence (PMID:24722437). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling." file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes EDNRA as transducing endothelin signals through heterotrimeric G proteins, especially Gq/11-calcium and ERK signaling.
GO:0003015 heart process	IMP PMID:25197047 Essential role of sympathetic endothelin A receptors for adv...	KEEP AS NON CORE	Summary: heart process is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0003015 heart process	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	KEEP AS NON CORE	Summary: heart process is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0007411 axon guidance	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: axon guidance is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0035904 aorta development	IMP PMID:14585980 Cardiomyocyte-specific endothelin A receptor knockout mice h...	KEEP AS NON CORE	Summary: aorta development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0002027 regulation of heart rate	IMP PMID:16399858 Blood pressure regulation by ETA and ETB receptors in consci...	KEEP AS NON CORE	Summary: regulation of heart rate is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0002027 regulation of heart rate	IGI PMID:16399858 Blood pressure regulation by ETA and ETB receptors in consci...	KEEP AS NON CORE	Summary: regulation of heart rate is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0008217 regulation of blood pressure	IMP PMID:16399858 Blood pressure regulation by ETA and ETB receptors in consci...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0008217 regulation of blood pressure	IGI PMID:16399858 Blood pressure regulation by ETA and ETB receptors in consci...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0007411 axon guidance	IMP PMID:18401410 Endothelins are vascular-derived axonal guidance cues for de...	KEEP AS NON CORE	Summary: axon guidance is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0014034 neural crest cell fate commitment	IMP PMID:17294360 Fate of cranial neural crest cells during craniofacial devel...	KEEP AS NON CORE	Summary: neural crest cell fate commitment is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0048675 axon extension	IMP PMID:18401410 Endothelins are vascular-derived axonal guidance cues for de...	KEEP AS NON CORE	Summary: axon extension is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0060324 face development	IDA PMID:18199583 Recombinase-mediated cassette exchange reveals the selective...	KEEP AS NON CORE	Summary: face development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0060324 face development	IMP PMID:18199583 Recombinase-mediated cassette exchange reveals the selective...	KEEP AS NON CORE	Summary: face development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0097152 mesenchymal cell apoptotic process	IMP PMID:17294360 Fate of cranial neural crest cells during craniofacial devel...	KEEP AS NON CORE	Summary: mesenchymal cell apoptotic process is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:1904888 cranial skeletal system development	IMP PMID:17294360 Fate of cranial neural crest cells during craniofacial devel...	KEEP AS NON CORE	Summary: cranial skeletal system development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:1904888 cranial skeletal system development	IDA PMID:18199583 Recombinase-mediated cassette exchange reveals the selective...	KEEP AS NON CORE	Summary: cranial skeletal system development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:1904888 cranial skeletal system development	IMP PMID:18199583 Recombinase-mediated cassette exchange reveals the selective...	KEEP AS NON CORE	Summary: cranial skeletal system development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0044751 cellular response to human chorionic gonadotropin stimulus	IDA PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	KEEP AS NON CORE	Summary: cellular response to human chorionic gonadotropin stimulus is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0044751 cellular response to human chorionic gonadotropin stimulus	IMP PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	KEEP AS NON CORE	Summary: cellular response to human chorionic gonadotropin stimulus is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0071372 cellular response to follicle-stimulating hormone stimulus	IDA PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	KEEP AS NON CORE	Summary: cellular response to follicle-stimulating hormone stimulus is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0071373 cellular response to luteinizing hormone stimulus	IDA PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	KEEP AS NON CORE	Summary: cellular response to luteinizing hormone stimulus is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:1903537 meiotic cell cycle process involved in oocyte maturation	IMP PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	KEEP AS NON CORE	Summary: meiotic cell cycle process involved in oocyte maturation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0000278 mitotic cell cycle	IMP PMID:20929948 Endothelin receptor type A expression defines a distinct car...	MARK AS OVER ANNOTATED	Summary: mitotic cell cycle is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0003207 cardiac chamber formation	IMP PMID:20929948 Endothelin receptor type A expression defines a distinct car...	KEEP AS NON CORE	Summary: cardiac chamber formation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0003220 left ventricular cardiac muscle tissue morphogenesis	IMP PMID:20929948 Endothelin receptor type A expression defines a distinct car...	KEEP AS NON CORE	Summary: left ventricular cardiac muscle tissue morphogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0003228 atrial cardiac muscle tissue development	IMP PMID:20929948 Endothelin receptor type A expression defines a distinct car...	KEEP AS NON CORE	Summary: atrial cardiac muscle tissue development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0008217 regulation of blood pressure	IGI PMID:18784261 Combined knockout of collecting duct endothelin A and B rece...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0010467 gene expression	IMP PMID:20929948 Endothelin receptor type A expression defines a distinct car...	MARK AS OVER ANNOTATED	Summary: gene expression is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0014033 neural crest cell differentiation	IMP PMID:19185569 Elucidating timing and function of endothelin-A receptor sig...	KEEP AS NON CORE	Summary: neural crest cell differentiation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0035050 embryonic heart tube development	IMP PMID:20929948 Endothelin receptor type A expression defines a distinct car...	KEEP AS NON CORE	Summary: embryonic heart tube development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0042474 middle ear morphogenesis	IMP PMID:19185569 Elucidating timing and function of endothelin-A receptor sig...	KEEP AS NON CORE	Summary: middle ear morphogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0055078 sodium ion homeostasis	IGI PMID:18784261 Combined knockout of collecting duct endothelin A and B rece...	KEEP AS NON CORE	Summary: sodium ion homeostasis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:1904888 cranial skeletal system development	IMP PMID:19185569 Elucidating timing and function of endothelin-A receptor sig...	KEEP AS NON CORE	Summary: cranial skeletal system development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0001525 angiogenesis	IGI PMID:24043815 Endothelin-2 signaling in the neural retina promotes the end...	KEEP AS NON CORE	Summary: angiogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0001569 branching involved in blood vessel morphogenesis	IMP PMID:23933587 Endothelin regulates neural crest deployment and fate to for...	KEEP AS NON CORE	Summary: branching involved in blood vessel morphogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0014033 neural crest cell differentiation	IMP PMID:23933587 Endothelin regulates neural crest deployment and fate to for...	KEEP AS NON CORE	Summary: neural crest cell differentiation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0014034 neural crest cell fate commitment	IMP PMID:23933587 Endothelin regulates neural crest deployment and fate to for...	KEEP AS NON CORE	Summary: neural crest cell fate commitment is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0061626 pharyngeal arch artery morphogenesis	IMP PMID:23933587 Endothelin regulates neural crest deployment and fate to for...	KEEP AS NON CORE	Summary: pharyngeal arch artery morphogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0070294 renal sodium ion absorption	IMP PMID:23698114 Endothelin-1 inhibits sodium reabsorption by ET(A) and ET(B)...	KEEP AS NON CORE	Summary: renal sodium ion absorption is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0001974 blood vessel remodeling	IMP PMID:25197047 Essential role of sympathetic endothelin A receptors for adv...	KEEP AS NON CORE	Summary: blood vessel remodeling is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0007005 mitochondrion organization	IDA PMID:27899487 Glomerular Endothelial Mitochondrial Dysfunction Is Essentia...	MARK AS OVER ANNOTATED	Summary: mitochondrion organization is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0007382 specification of segmental identity, maxillary segment	IMP PMID:19017795 An endothelin-1 switch specifies maxillomandibular identity.	KEEP AS NON CORE	Summary: specification of segmental identity, maxillary segment is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0007507 heart development	IMP PMID:25197047 Essential role of sympathetic endothelin A receptors for adv...	KEEP AS NON CORE	Summary: heart development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0008217 regulation of blood pressure	IMP PMID:24412386 Smooth muscle specific disruption of the endothelin-A recept...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0009611 response to wounding	IMP PMID:25197047 Essential role of sympathetic endothelin A receptors for adv...	KEEP AS NON CORE	Summary: response to wounding is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0014033 neural crest cell differentiation	IGI PMID:28455376 Negative regulation of endothelin signaling by SIX1 is requi...	KEEP AS NON CORE	Summary: neural crest cell differentiation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0016322 neuron remodeling	IMP PMID:19017795 An endothelin-1 switch specifies maxillomandibular identity.	MARK AS OVER ANNOTATED	Summary: neuron remodeling is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0030878 thyroid gland development	IMP PMID:26506449 Postotic and preotic cranial neural crest cells differently ...	KEEP AS NON CORE	Summary: thyroid gland development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0032835 glomerulus development	IMP PMID:27899487 Glomerular Endothelial Mitochondrial Dysfunction Is Essentia...	KEEP AS NON CORE	Summary: glomerulus development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0034599 cellular response to oxidative stress	IMP PMID:27899487 Glomerular Endothelial Mitochondrial Dysfunction Is Essentia...	MARK AS OVER ANNOTATED	Summary: cellular response to oxidative stress is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0042305 specification of segmental identity, mandibular segment	IMP PMID:19017795 An endothelin-1 switch specifies maxillomandibular identity.	KEEP AS NON CORE	Summary: specification of segmental identity, mandibular segment is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0042415 norepinephrine metabolic process	IMP PMID:25197047 Essential role of sympathetic endothelin A receptors for adv...	KEEP AS NON CORE	Summary: norepinephrine metabolic process is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0048485 sympathetic nervous system development	IMP PMID:25197047 Essential role of sympathetic endothelin A receptors for adv...	KEEP AS NON CORE	Summary: sympathetic nervous system development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0048706 embryonic skeletal system development	IGI PMID:19017795 An endothelin-1 switch specifies maxillomandibular identity.	KEEP AS NON CORE	Summary: embryonic skeletal system development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0050905 neuromuscular process	IMP PMID:19017795 An endothelin-1 switch specifies maxillomandibular identity.	KEEP AS NON CORE	Summary: neuromuscular process is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0097018 renal albumin absorption	IMP PMID:27899487 Glomerular Endothelial Mitochondrial Dysfunction Is Essentia...	KEEP AS NON CORE	Summary: renal albumin absorption is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0097084 vascular associated smooth muscle cell development	IMP PMID:24412386 Smooth muscle specific disruption of the endothelin-A recept...	KEEP AS NON CORE	Summary: vascular associated smooth muscle cell development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:1903210 podocyte apoptotic process	IMP PMID:27899487 Glomerular Endothelial Mitochondrial Dysfunction Is Essentia...	KEEP AS NON CORE	Summary: podocyte apoptotic process is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0001975 response to amphetamine	IMP PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	KEEP AS NON CORE	Summary: response to amphetamine is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0003253 cardiac neural crest cell migration involved in outflow tract morphogenesis	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	KEEP AS NON CORE	Summary: cardiac neural crest cell migration involved in outflow tract morphogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0003357 noradrenergic neuron differentiation	IMP PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	KEEP AS NON CORE	Summary: noradrenergic neuron differentiation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0006468 protein phosphorylation	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	MARK AS OVER ANNOTATED	Summary: protein phosphorylation is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0007507 heart development	IMP PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	KEEP AS NON CORE	Summary: heart development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0008217 regulation of blood pressure	IMP PMID:26531127 Age-dependent blood pressure elevation is due to increased v...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation.
GO:0010467 gene expression	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	MARK AS OVER ANNOTATED	Summary: gene expression is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0010467 gene expression	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	MARK AS OVER ANNOTATED	Summary: gene expression is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0031175 neuron projection development	IMP PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	KEEP AS NON CORE	Summary: neuron projection development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0031175 neuron projection development	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: neuron projection development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0035050 embryonic heart tube development	IMP PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	KEEP AS NON CORE	Summary: embryonic heart tube development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0035050 embryonic heart tube development	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: embryonic heart tube development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0035050 embryonic heart tube development	IGI PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: embryonic heart tube development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0035050 embryonic heart tube development	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	KEEP AS NON CORE	Summary: embryonic heart tube development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0035904 aorta development	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	KEEP AS NON CORE	Summary: aorta development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0060385 axonogenesis involved in innervation	IMP PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	KEEP AS NON CORE	Summary: axonogenesis involved in innervation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0060385 axonogenesis involved in innervation	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: axonogenesis involved in innervation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0061626 pharyngeal arch artery morphogenesis	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	KEEP AS NON CORE	Summary: pharyngeal arch artery morphogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0071526 semaphorin-plexin signaling pathway	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: semaphorin-plexin signaling pathway is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0086100 endothelin receptor signaling pathway	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	ACCEPT	Summary: endothelin receptor signaling pathway is biologically consistent with the curated synthesis for Ednra and is supported by IMP evidence (PMID:31219639). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling." file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes EDNRA as transducing endothelin signals through heterotrimeric G proteins, especially Gq/11-calcium and ERK signaling.
GO:0097492 sympathetic neuron axon guidance	IGI PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: sympathetic neuron axon guidance is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:1905144 response to acetylcholine	IMP PMID:26531127 Age-dependent blood pressure elevation is due to increased v...	MARK AS OVER ANNOTATED	Summary: response to acetylcholine is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:1905871 regulation of protein localization to cell leading edge	IMP PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	MARK AS OVER ANNOTATED	Summary: regulation of protein localization to cell leading edge is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons.
GO:0003094 glomerular filtration	IDA PMID:31402170 Endothelin receptor-A mediates degradation of the glomerular...	KEEP AS NON CORE	Summary: glomerular filtration is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0005886 plasma membrane	IDA PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Ednra and is supported by IDA evidence (PMID:30990108). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA as a 7-transmembrane class A GPCR functioning at the plasma membrane of target cells.
GO:0006874 intracellular calcium ion homeostasis	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: This DRG pain study supports ETAR/TRPA1 sensitization rather than a core intracellular calcium homeostasis annotation. Reason: ET-1 did not induce robust calcium signals in native mouse DRG neurons; Ednra calcium signaling is better captured by the more specific retained cytosolic-calcium and podocyte calcium annotations. Supporting Evidence: PMID:30990108 Application of ET-1 (100 nM) did not induce strong Ca2+ signals in mouse DRG neurons as in HEK293 cells
GO:0006874 intracellular calcium ion homeostasis	IMP PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: This DRG pain study supports ETAR/TRPA1 sensitization rather than a core intracellular calcium homeostasis annotation. Reason: ET-1 did not induce robust calcium signals in native mouse DRG neurons; Ednra calcium signaling is better captured by the more specific retained cytosolic-calcium and podocyte calcium annotations. Supporting Evidence: PMID:30990108 Application of ET-1 (100 nM) did not induce strong Ca2+ signals in mouse DRG neurons as in HEK293 cells
GO:0010467 gene expression	IGI PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	MARK AS OVER ANNOTATED	Summary: gene expression is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0060070 canonical Wnt signaling pathway	IGI PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	KEEP AS NON CORE	Summary: canonical Wnt signaling pathway is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 treatment with endothelin-1 increased total β-catenin and phospho-NF-κB expression in wild-type glomeruli, but this effect was attenuated in Pod-ETRKO glomeruli.
GO:0070301 cellular response to hydrogen peroxide	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	KEEP AS NON CORE	Summary: cellular response to hydrogen peroxide is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:30990108 ET-1 sensitizes TRPA1 channel activated by endogenous agonist H2O2
GO:0070588 calcium ion transmembrane transport	IDA PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	KEEP AS NON CORE	Summary: calcium ion transmembrane transport is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0070588 calcium ion transmembrane transport	IMP PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	KEEP AS NON CORE	Summary: calcium ion transmembrane transport is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0070588 calcium ion transmembrane transport	IGI PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	KEEP AS NON CORE	Summary: calcium ion transmembrane transport is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:24722437 Stimulation of primary mouse podocytes with endothelin-1 elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs).
GO:0072011 glomerular endothelium development	IDA PMID:31402170 Endothelin receptor-A mediates degradation of the glomerular...	KEEP AS NON CORE	Summary: glomerular endothelium development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0072112 podocyte differentiation	IDA PMID:31402170 Endothelin receptor-A mediates degradation of the glomerular...	KEEP AS NON CORE	Summary: podocyte differentiation is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0086100 endothelin receptor signaling pathway	IGI PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	ACCEPT	Summary: endothelin receptor signaling pathway is biologically consistent with the curated synthesis for Ednra and is supported by IGI evidence (PMID:24722437). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling." file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes EDNRA as transducing endothelin signals through heterotrimeric G proteins, especially Gq/11-calcium and ERK signaling.
GO:0097018 renal albumin absorption	IDA PMID:31402170 Endothelin receptor-A mediates degradation of the glomerular...	KEEP AS NON CORE	Summary: renal albumin absorption is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism.
GO:0097237 cellular response to toxic substance	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: cellular response to toxic substance is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0097237 cellular response to toxic substance	IDA PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: cellular response to toxic substance is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0097237 cellular response to toxic substance	IMP PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: cellular response to toxic substance is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0141156 cAMP/PKA signal transduction	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	KEEP AS NON CORE	Summary: cAMP/PKA signal transduction is supported in a DRG pain-sensitization context but is not the core EDNRA receptor function. Reason: PMID:30990108 supports ETAR-PKA-mediated TRPA1 sensitization; this is a context-specific nociceptive signaling branch rather than the central endothelin receptor/PLC/calcium pathway. Supporting Evidence: PMID:30990108 ET-1-induced sensitization of TRPA1 in vitro requires ETAR-mediated PKA signaling pathway.
GO:2001259 positive regulation of cation channel activity	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	KEEP AS NON CORE	Summary: positive regulation of cation channel activity is supported in a DRG TRPA1 sensitization context but is not core EDNRA receptor identity. Reason: PMID:30990108 directly supports ETAR-dependent TRPA1 channel sensitization as a pain-specific signaling output, so the term is retained as non-core rather than treated as the primary receptor function. Supporting Evidence: PMID:30990108 ET-1 sensitizes TRPA1 channel activated by endogenous agonist H2O2
GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IGI PMID:15928212 Collecting duct-specific knockout of the endothelin A recept...	MARK AS OVER ANNOTATED	Summary: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0010827 regulation of D-glucose transmembrane transport	IDA PMID:11546805 beta -Arrestin-mediated recruitment of the Src family kinase...	KEEP AS NON CORE	Summary: regulation of D-glucose transmembrane transport is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0060322 head development	IMP PMID:15306564 Endothelin-A receptor-dependent and -independent signaling p...	KEEP AS NON CORE	Summary: head development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0014032 neural crest cell development	IMP PMID:15306564 Endothelin-A receptor-dependent and -independent signaling p...	KEEP AS NON CORE	Summary: neural crest cell development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0005515 protein binding	IPI PMID:11546805 beta -Arrestin-mediated recruitment of the Src family kinase...	REMOVE	Summary: protein binding is not supported as an appropriate annotation for Ednra after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Ednra biology. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0001666 response to hypoxia	IMP PMID:9449664 Cranial and cardiac neural crest defects in endothelin-A rec...	MARK AS OVER ANNOTATED	Summary: response to hypoxia is related to reported Ednra biology only as a broad downstream readout or generic interaction term. Reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0001701 in utero embryonic development	IMP PMID:15327783 Temporal requirement of signaling cascade involving endothel...	KEEP AS NON CORE	Summary: in utero embryonic development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0004962 endothelin receptor activity	IMP PMID:9449664 Cranial and cardiac neural crest defects in endothelin-A rec...	ACCEPT	Summary: endothelin receptor activity is biologically consistent with the curated synthesis for Ednra and is supported by IMP evidence (PMID:9449664). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon identifies EDNRA/ETA as an endothelin peptide receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the canonical receptor state.
GO:0005515 protein binding	IPI PMID:9449664 Cranial and cardiac neural crest defects in endothelin-A rec...	REMOVE	Summary: protein binding is not supported as an appropriate annotation for Ednra after review of the available mouse evidence. Reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Ednra biology. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here.
GO:0007585 respiratory gaseous exchange by respiratory system	IMP PMID:9449664 Cranial and cardiac neural crest defects in endothelin-A rec...	KEEP AS NON CORE	Summary: respiratory gaseous exchange by respiratory system is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0014032 neural crest cell development	IMP PMID:15327783 Temporal requirement of signaling cascade involving endothel...	KEEP AS NON CORE	Summary: neural crest cell development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0014032 neural crest cell development	IMP PMID:9449664 Cranial and cardiac neural crest defects in endothelin-A rec...	KEEP AS NON CORE	Summary: neural crest cell development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0042310 vasoconstriction	IMP PMID:9826706 Endothelin ETA receptor blockade restores NO-mediated endoth...	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Ednra and is supported by IMP evidence (PMID:9826706). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Ednra; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation. file:mouse/Ednra/Ednra-deep-research-falcon.md Falcon describes ETA/EDNRA as the principal receptor mediating ET-1-driven vascular smooth muscle vasoconstriction.
GO:0001569 branching involved in blood vessel morphogenesis	IGI PMID:15664398 Roles of forkhead transcription factor Foxc2 (MFH-1) and end...	KEEP AS NON CORE	Summary: branching involved in blood vessel morphogenesis is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0007507 heart development	IGI PMID:15664398 Roles of forkhead transcription factor Foxc2 (MFH-1) and end...	KEEP AS NON CORE	Summary: heart development is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0007585 respiratory gaseous exchange by respiratory system	IMP PMID:10626068 Endothelin in the central control of cardiovascular and resp...	KEEP AS NON CORE	Summary: respiratory gaseous exchange by respiratory system is supported for Ednra in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role. Reason: This annotation captures a real downstream or context-specific consequence of Ednra activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.
GO:0004930 G protein-coupled receptor activity	TAS PMID:11546805 beta -Arrestin-mediated recruitment of the Src family kinase...	MODIFY	Summary: G protein-coupled receptor activity captures the right general biology for Ednra, but a more specific GO term is available. Reason: The current term is too broad or less precise than endothelin receptor activity for this gene. Replace with endothelin receptor activity to align the annotation with the reviewed evidence. Proposed replacements: endothelin receptor activity Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor.
GO:0007186 G protein-coupled receptor signaling pathway	TAS PMID:11546805 beta -Arrestin-mediated recruitment of the Src family kinase...	MODIFY	Summary: G protein-coupled receptor signaling pathway captures the right general biology for Ednra, but a more specific GO term is available. Reason: The current term is too broad or less precise than endothelin receptor signaling pathway for this gene. Replace with endothelin receptor signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: endothelin receptor signaling pathway Supporting Evidence: file:mouse/Ednra/Ednra-notes.md Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures.

Core Functions

EDNRA is a plasma-membrane endothelin receptor that activates GPCR signaling in response to endothelin ligands, especially ET-1, coupling to phosphatidylinositol-calcium and small-GTPase pathways that control vasoconstriction and developmental patterning.

Molecular Function:

endothelin receptor activity

Directly Involved In:

endothelin receptor signaling pathway vasoconstriction positive regulation of cytosolic calcium ion concentration

Cellular Locations:

plasma membrane

Supporting Evidence:

file:mouse/Ednra/Ednra-notes.md
Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor.
file:mouse/Ednra/Ednra-deep-research-falcon.md
Falcon reinforces the core model that EDNRA is a plasma-membrane endothelin peptide GPCR mediating endothelin receptor signaling, vasoconstriction, calcium signaling, and mandibular neural crest patterning.

References

file:mouse/Ednra/Ednra-notes.md

Curator notes for mouse Ednra review

file:mouse/Ednra/Ednra-deep-research-falcon.md

Falcon deep research report for mouse Ednra

file:mouse/Ednra/Ednra-uniprot.txt

UniProtKB record for mouse Ednra

file:mouse/Ednra/Ednra-goa.tsv

QuickGO export for mouse Ednra

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10626068

Endothelin in the central control of cardiovascular and respiratory functions.

PMID:11546805

beta -Arrestin-mediated recruitment of the Src family kinase Yes mediates endothelin-1-stimulated glucose transport.

PMID:14585980

Cardiomyocyte-specific endothelin A receptor knockout mice have normal cardiac function and an unaltered hypertrophic response to angiotensin II and isoproterenol.

PMID:15306564

Endothelin-A receptor-dependent and -independent signaling pathways in establishing mandibular identity.

PMID:15327783

Temporal requirement of signaling cascade involving endothelin-1/endothelin receptor type A in branchial arch development.

PMID:15664398

Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin receptor A in cardiovascular morphogenesis.

PMID:15928212

Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure.

PMID:16399858

Blood pressure regulation by ETA and ETB receptors in conscious, telemetry-instrumented mice and role of ETA in hypertension produced by selective ETB blockade.

PMID:17294360

Fate of cranial neural crest cells during craniofacial development in endothelin-A receptor-deficient mice.

PMID:18199583

Recombinase-mediated cassette exchange reveals the selective use of Gq/G11-dependent and -independent endothelin 1/endothelin type A receptor signaling in pharyngeal arch development.

PMID:18401410

Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons.

PMID:18784261

Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention.

PMID:19017795

An endothelin-1 switch specifies maxillomandibular identity.

PMID:19111534

Paracrine regulation of the resumption of oocyte meiosis by endothelin-1.

PMID:19185569

Elucidating timing and function of endothelin-A receptor signaling during craniofacial development using neural crest cell-specific gene deletion and receptor antagonism.

PMID:20929948

Endothelin receptor type A expression defines a distinct cardiac subdomain within the heart field and is later implicated in chamber myocardium formation.

PMID:23698114

Endothelin-1 inhibits sodium reabsorption by ET(A) and ET(B) receptors in the mouse cortical collecting duct.

PMID:23933587

Endothelin regulates neural crest deployment and fate to form great vessels through Dlx5/Dlx6-independent mechanisms.

PMID:24043815

Endothelin-2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis.

PMID:24412386

Smooth muscle specific disruption of the endothelin-A receptor in mice reduces arterial pressure, and vascular reactivity and affects vascular development.

PMID:24722437

Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis.

PMID:24875861

Venous endothelin guides sympathetic innervation of the developing mouse heart.

PMID:25197047

Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling.

PMID:26506449

Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

PMID:26531127

Age-dependent blood pressure elevation is due to increased vascular smooth muscle tone mediated by G-protein signalling.

PMID:27899487

Glomerular Endothelial Mitochondrial Dysfunction Is Essential and Characteristic of Diabetic Kidney Disease Susceptibility.

PMID:28455376

Negative regulation of endothelin signaling by SIX1 is required for proper maxillary development.

PMID:30735130

Venous endothelin modulates responsiveness of cardiac sympathetic axons to arterial semaphorin.

PMID:30990108

ET(A)R and protein kinase A pathway mediate ET-1 sensitization of TRPA1 channel: A molecular mechanism of ET-1-induced mechanical hyperalgesia.

PMID:31219639

Cdc42 activation by endothelin regulates neural crest cell migration in the cardiac outflow tract.

PMID:31402170

Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells.

PMID:9449664

Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice.

PMID:9826706

Endothelin ETA receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice.

Suggested Experiments

Experiment: In cranial/cardiac neural crest models, rescue Ednra loss with pathway-selective receptor mutants and assay Dlx/Hand2 expression, Cdc42 localization, and outflow-tract migration.

Hypothesis: EDNRA developmental functions are mediated by specific Gq/G11 and Cdc42 pathway branches rather than generic GPCR signaling.

Type: pathway-selective rescue

📚 Additional Documentation

Deep Research Falcon

(Ednra-deep-research-falcon.md)

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protein_domains: Endthln_rcpt. (IPR000499); ETA_rcpt. (IPR002175); GPCR_endothelin_rcpt.
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q61614
Protein Description: RecName: Full=Endothelin-1 receptor {ECO:0000305}; AltName: Full=Endothelin receptor type A {ECO:0000312|MGI:MGI:105923}; Short=ET-A; Short=ET-AR; Flags: Precursor;
Gene Information: Name=Ednra {ECO:0000312|MGI:MGI:105923}; Synonyms=Gpcr10;
Organism (full): Mus musculus (Mouse).
Protein Family: Belongs to the G-protein coupled receptor 1 family.
Key Domains: Endthln_rcpt. (IPR000499); ETA_rcpt. (IPR002175); GPCR_endothelin_rcpt. (IPR051193); GPCR_Rhodpsn. (IPR000276); GPCR_Rhodpsn_7TM. (IPR017452)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Ednra" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Ednra' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Ednra (gene ID: Ednra, UniProt: Q61614) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q61614
Protein Description: RecName: Full=Endothelin-1 receptor {ECO:0000305}; AltName: Full=Endothelin receptor type A {ECO:0000312|MGI:MGI:105923}; Short=ET-A; Short=ET-AR; Flags: Precursor;
Gene Information: Name=Ednra {ECO:0000312|MGI:MGI:105923}; Synonyms=Gpcr10;
Organism (full): Mus musculus (Mouse).
Protein Family: Belongs to the G-protein coupled receptor 1 family.
Key Domains: Endthln_rcpt. (IPR000499); ETA_rcpt. (IPR002175); GPCR_endothelin_rcpt. (IPR051193); GPCR_Rhodpsn. (IPR000276); GPCR_Rhodpsn_7TM. (IPR017452)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Ednra" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene Ednra (gene ID: Ednra, UniProt: Q61614) in mouse.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Research report: Mouse Ednra (UniProt Q61614) — functional annotation and recent literature (2023–2024 prioritized)

1) Target verification (mandatory)

The UniProt accession Q61614 corresponds to mouse Ednra (syn. Gpcr10), encoding endothelin receptor type A (ETAR/ETA/EDNRA), a class A (rhodopsin-like) 7-transmembrane G protein–coupled receptor (GPCR). This identity is consistent with mechanistic work explicitly describing ETAR as a class A GPCR and studying mouse Ednra knock-in models. (kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 2-3)

2) Key concepts and definitions (current understanding)

2.1 Endothelin system overview and EDNRA’s role

The endothelin system is centered on endothelin peptides (ET-1/ET-2/ET-3) and endothelin receptors. ETA/EDNRA is described as the principal receptor mediating ET‑1–driven vasoconstriction in the vasculature and producing strong, sustained constrictor responses; it is functionally localized on vascular smooth muscle, where ETA antagonism can reverse ET‑1–mediated constriction. (abraham2023currentandfuture pages 1-4, abraham2023currentandfuture pages 39-46)

In craniofacial development, EDNRA acts as the receptor for EDN1 in pharyngeal arch contexts and is central for mandibular (lower jaw) identity specification in neural crest derivatives. (kurihara2023mandibulofacialdysostosiswith pages 1-2, seto2024invitroinduction pages 9-10)

2.2 Molecular function (what the protein does)

EDNRA is a peptide hormone receptor GPCR that binds endothelins and transduces signals by activating heterotrimeric G proteins. In its canonical state, ETAR shows higher affinity for ET1 and ET2 than ET3, though receptor variants can shift ligand preference. (kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 4-5)

2.3 Subcellular/cellular localization (where it acts)

Functionally, EDNRA is primarily described on vascular smooth muscle cells (VSMCs) mediating ET‑1 constriction; ET‑1/ETA complexes can undergo endosomal internalization, with potential receptor recycling to the plasma membrane. (abraham2023currentandfuture pages 39-46)

EDNRA signaling is also functionally implicated in the kidney nephron/collecting duct, where genetic evidence indicates ETA in these compartments contributes to sodium/water handling relevant to drug side effects (fluid retention). (abraham2023currentandfuture pages 4-7)

2.4 Core signaling pathways downstream of EDNRA

A central downstream signaling mode is Gq/11 coupling, which increases intracellular Ca2+ and activates ERK phosphorylation, consistent with ETAR’s roles in contraction and mitogenic signaling. (kurihara2023mandibulofacialdysostosiswith pages 2-3, kurihara2023mandibulofacialdysostosiswith pages 4-5)

Recent mechanistic work also supports signaling diversification/“bias” including G12/13 engagement (linked to RhoA/MLCK and mitogenic outputs) and context-dependent Gs/cAMP signaling. (gyamfi2024thestructuraland pages 48-51, gyamfi2024thestructuraland pages 54-58)

3) Recent developments and latest research (2023–2024)

3.1 2023: Allosteric GPCR mechanisms and craniofacial disease—EDNRA gain-of-function

A high-impact 2023 study (Kurihara et al., Journal of Clinical Investigation, Feb 2023; https://doi.org/10.1172/jci151536) established that mandibulofacial dysostosis with alopecia (MFDA) can result from EDNRA gain-of-function missense variants and explained these using allosteric GPCR mechanisms.

Key mechanistic concepts from this work:
- ETAR activation involves orthosteric agonist binding and outward movement of TM6 to accommodate G-protein binding; G-protein binding can allosterically enhance agonist affinity. A conserved Na+/water pocket stabilizes the inactive state. (kurihara2023mandibulofacialdysostosiswith pages 1-2)
- E303K (intracellular end of TM6) increases TM6 flexibility and favors G-protein engagement, increasing agonist affinity; Y129F (under ligand pocket) disrupts the sodium-water network to favor ET3 binding. (kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 8-11)

Quantitative/mechanistic results (useful for functional annotation):
- Disease-associated variants increase ET3 affinity (reported approximately ~27-fold for Y129F and ~10- to 5-fold for E303K across assays) and potentiate Gq/11 outputs; E303K also increases basal signaling in ligand-free Ca2+/IP1 readouts. (kurihara2023mandibulofacialdysostosiswith pages 4-5)
- In cell assays, variants enhance ET3-induced ERK phosphorylation and intracellular Ca2+ mobilization; Gq/11 coupling is implicated as a key mediator. (kurihara2023mandibulofacialdysostosiswith pages 2-3, kurihara2023mandibulofacialdysostosiswith pages 4-5)

Developmental interpretation:
- In craniofacial development, EDN1–EDNRA signaling to ETAR-expressing migrating cranial neural crest specifies lower-jaw identity; loss leads to transformations/duplications, and inappropriate activation can drive fate conversion. (kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 2-3)

Visual evidence supporting the ET3-dependence and rescue concept:
- Kurihara et al. provide figure panels showing craniofacial phenotype rescue of EDNRA GOF mutants by Edn3 deletion and schematic models of mutant receptor activation. (kurihara2023mandibulofacialdysostosiswith media 5cc1a389, kurihara2023mandibulofacialdysostosiswith media 2cece4c7, kurihara2023mandibulofacialdysostosiswith media 00ca822b)

3.2 2024: Human PSC branchial-arch model recapitulating EDN1–EDNRA jaw patterning logic

Seto et al. (Nature Communications, Feb 2024; https://doi.org/10.1038/s41467-024-45285-0) developed a patterned branchial-arch-like aggregate model from human pluripotent stem cells.

Relevance to EDNRA functional annotation:
- NCC-like cells in the model express EDNRA, and the authors interpret EDN1 signaling as governing maxillary vs mandibular fate, with EDN1 promoting mandibular specifiers such as DLX5/6; low EDN1 levels in the model are hypothesized to favor maxillary-like identity. (seto2024invitroinduction pages 9-10)

Although this is not a mouse experiment, it provides recent experimental support for a conserved EDN1–EDNRA developmental logic aligned with mouse genetic findings. (seto2024invitroinduction pages 9-10)

3.3 2024: Vascular omics/network placement of EDNRA

Zhu et al. (Communications Biology, Jan 2024; https://doi.org/10.1038/s42003-023-05705-1) included EDNRA as a CAD index protein in interaction proteomics.

Key points:
- EDNRA was used as bait in IP-MS to build cell-type-specific protein interaction networks in primary human aortic endothelial cells and human coronary artery smooth muscle cells; smooth muscle networks showed enrichment for CAD-associated variants. (zhu2024proteininteractionnetworks pages 1-2)

This supports EDNRA’s operational relevance in vascular smooth muscle disease biology and provides a modern systems-level framework, although EDNRA-specific interactor lists/quantitation are not present in the retrieved pages. (zhu2024proteininteractionnetworks pages 1-2)

3.4 2024: EDNRA as an autoantigen/functional target in systemic sclerosis

Binda et al. (International Journal of Molecular Sciences, Feb 2024; https://doi.org/10.3390/ijms25042299) reviewed autoantibodies targeting GPCRs in systemic sclerosis (SSc).

Key points:
- Anti-ETAR (anti-EDNRA) autoantibodies are associated with severe vasculopathic manifestations in SSc, and are implicated in PAH and dilated cardiomyopathy contexts. (binda2024autoantibodiestargetinggproteincoupled pages 1-2)

A 2024 mechanistic source further suggests ETAR-targeting autoantibodies can be agonistic and may produce distinct signaling outputs (higher cAMP than ET-1 in a VSMC cell line), highlighting potential signaling bias/complexity. (gyamfi2024thestructuralanda pages 54-58, gyamfi2024thestructuraland pages 54-58)

4) Current applications and real-world implementations

4.1 Pharmacologic EDNRA targeting: ETA antagonists and beyond

A 2023 review focused on cardiovascular strategy (Abraham et al., Dec 2023; https://doi.org/10.17863/cam.104737) describes ETA antagonism as an established therapeutic approach, historically limited to pulmonary arterial hypertension (PAH) but with renewed interest across cardiovascular diseases. (abraham2023currentandfuture pages 1-4)

Clinical/real-world and translational highlights:
- ETA antagonists can produce clinically meaningful vasodilation in humans; ETA is the primary receptor mediating sustained ET‑1 constriction in vessels. (abraham2023currentandfuture pages 1-4, abraham2023currentandfuture pages 39-46)
- A critical on-target limitation is fluid retention/edema, tied to renal endothelin biology (see quantitative statistics below). (abraham2023currentandfuture pages 1-4, abraham2023currentandfuture pages 4-7)

Emerging modality: anti-EDNRA monoclonal antibody
- The same review describes getagozumab (GMA301), a humanized anti-ETA monoclonal antibody, providing quantitative binding and PK parameters and noting ongoing PAH trials to assess safety signals including fluid retention. (abraham2023currentandfuture pages 7-11)

4.2 Developmental biology applications

EDNRA signaling is a major pathway node used to:
- Interpret and experimentally manipulate jaw patterning and cranial neural crest fate decisions. (kurihara2023mandibulofacialdysostosiswith pages 1-2, seto2024invitroinduction pages 9-10)
- Construct mechanistic genotype-to-phenotype models for craniofacial disorders caused by GPCR allostery and ligand bias. (kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 4-5)

5) Expert opinions and analysis (authoritative synthesis)

5.1 EDNRA/ETA as a central vasoconstrictor axis

The 2023 cardiovascular strategy review frames ETA as the dominant receptor driving ET‑1 vasoconstriction in the arterial wall and notes that translational work has “reignited” interest in targeting the endothelin pathway beyond PAH. (abraham2023currentandfuture pages 1-4)

Mechanistic interpretation consistent with these views is supported by functional localization to VSMCs and pharmacologic reversal of ET‑1 constriction by ETA antagonists. (abraham2023currentandfuture pages 39-46)

5.2 EDNRA as an instructive developmental signaling receptor

Recent primary evidence and discussion emphasize EDNRA not merely as permissive signaling but as instructive for tissue identity (mandibular fate) in cranial neural crest-derived structures, with both loss-of-function and ectopic activation producing predictable homeotic transformations. (kurihara2023mandibulofacialdysostosiswith pages 1-2, seto2024invitroinduction pages 9-10)

5.3 EDNRA signaling complexity and bias

The 2024 mechanistic evidence indicates that EDNRA can engage multiple G-protein pathways and that non-canonical agonists (e.g., autoantibodies) may produce distinct outputs (e.g., cAMP differences), supporting the modern view of biased agonism/state dependence in GPCR biology. (gyamfi2024thestructuraland pages 48-51, gyamfi2024thestructuraland pages 54-58)

6) Relevant statistics and data (recent studies)

6.1 Quantitative molecular pharmacology/biophysics (2023)

EDNRA GOF variants: ET3 binding affinity increases were reported as approximately ~27× (Y129F) and ~10- to 5× (E303K) across assays; E303K also showed enhanced ligand-free signaling in Ca2+/IP1 readouts and increased Gαq activation. (kurihara2023mandibulofacialdysostosiswith pages 4-5)

6.2 Clinical/real-world adverse event rates and drug statistics (2023)

In PAH patients receiving bosentan, peripheral edema occurred in ~17% of patients (as reported in the review’s cited clinical context). (abraham2023currentandfuture pages 1-4)

6.3 Quantitative clinical PK/PD for anti-ETA biologic (2023)

Getagozumab (GMA301): equilibrium dissociation constant Kd ~8.7 nM, IC50 38 nM; first-in-human half-life ~21 days (compared with ~15 h for ambrisentan in the same discussion). (abraham2023currentandfuture pages 7-11)

6.4 Human population genetics statistics relevant to EDNRA regulation (2023)

Variant rs9349379 minor G allele frequency reported as ~40% in population data; variants at/near EDNRA were discussed as influencing transcriptional activity and vascular disease risk. (abraham2023currentandfuture pages 4-7)

7) Practical functional annotation summary (mouse Ednra / Q61614)

Molecular function: endothelin peptide receptor (ETA) GPCR binding endothelins (ET1/ET2>ET3 baseline) and transducing signals through heterotrimeric G proteins. (kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 4-5)

Primary pathways: Gq/11 → PLC signaling → Ca2+ mobilization and ERK activation (core); additional evidence supports G12/13 and context-dependent Gs/cAMP outputs, consistent with pathway diversity/bias. (kurihara2023mandibulofacialdysostosiswith pages 2-3, gyamfi2024thestructuraland pages 48-51, gyamfi2024thestructuraland pages 54-58)

Localization: plasma membrane of target cells; functionally localized on vascular smooth muscle (vasoconstriction) and implicated in nephron/collecting duct (fluid handling). Evidence also supports internalization/recycling behavior typical of GPCRs. (abraham2023currentandfuture pages 39-46, abraham2023currentandfuture pages 4-7)

Developmental role: EDN1–EDNRA signaling in cranial neural crest derivatives instructs mandibular identity; gain-of-function variants can cause ET3-dependent ectopic signaling and craniofacial patterning defects, with Edn3 deletion rescuing phenotypes in mouse models. (kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 2-3, kurihara2023mandibulofacialdysostosiswith media 5cc1a389)

8) Evidence summary table

Aspect	Key findings	Evidence	Source
Identity	Mouse Ednra (UniProt Q61614) corresponds to endothelin receptor type A / ETAR / ETA, a class A (rhodopsin-like) GPCR with 7TM architecture; retrieved literature consistently matches this identity and receptor family.	(kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 2-3)	Kurihara et al., J Clin Invest (Feb 2023), https://doi.org/10.1172/jci151536
Ligands	ETAR binds endothelin peptides, with higher affinity for ET1 and ET2 than ET3 in the canonical state; 2023 work showed disease-associated EDNRA variants can shift responsiveness to ET3.	(kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 4-5)	Kurihara et al., J Clin Invest (Feb 2023), https://doi.org/10.1172/jci151536
Signaling	Core signaling is Gq/11-coupled, driving intracellular Ca2+ mobilization and ERK phosphorylation; 2024 mechanistic work also supports signaling via G12/13 and context-dependent Gs/cAMP outputs, indicating signaling bias/state dependence.	(kurihara2023mandibulofacialdysostosiswith pages 2-3, gyamfi2024thestructuraland pages 48-51, gyamfi2024thestructuraland pages 54-58)	Kurihara et al., J Clin Invest (Feb 2023), https://doi.org/10.1172/jci151536; Gyamfi (2024), source text available in evidence corpus
Localization	Functionally localized primarily to vascular smooth muscle, where ETA mediates sustained vasoconstriction; ETAR is also functionally implicated in kidney nephron/collecting duct and is expressed in cranial neural crest-like cells in jaw-patterning contexts.	(abraham2023currentandfuture pages 1-4, seto2024invitroinduction pages 9-10, abraham2023currentandfuture pages 39-46)	Abraham et al. (Dec 2023), https://doi.org/10.17863/cam.104737; Seto et al., Nat Commun (Feb 2024), https://doi.org/10.1038/s41467-024-45285-0
Developmental roles	EDN1–EDNRA signaling specifies lower-jaw/mandibular identity in pharyngeal arch neural crest; loss of pathway activity causes upper-jaw duplication/homeotic transformation, whereas excess activation can convert maxillary toward mandibular fate.	(kurihara2023mandibulofacialdysostosiswith pages 1-2, kurihara2023mandibulofacialdysostosiswith pages 2-3, seto2024invitroinduction pages 9-10)	Kurihara et al., J Clin Invest (Feb 2023), https://doi.org/10.1172/jci151536; Seto et al., Nat Commun (Feb 2024), https://doi.org/10.1038/s41467-024-45285-0
Disease/phenotypes	Gain-of-function EDNRA mutations (Y129F, E303K) cause craniofacial patterning defects consistent with mandibulofacial dysostosis with alopecia; in mouse models, phenotypes reflect ectopic/ET3-dependent activation and altered skeletal identity.	(kurihara2023mandibulofacialdysostosiswith pages 2-3, kurihara2023mandibulofacialdysostosiswith pages 4-5, kurihara2023mandibulofacialdysostosiswith media 5cc1a389)	Kurihara et al., J Clin Invest (Feb 2023), https://doi.org/10.1172/jci151536
Pharmacology/applications	ETA antagonism is a major translational application of EDNRA biology, established in pulmonary arterial hypertension and under broader cardiovascular investigation; clinical interest includes selective antagonists and anti-ETA biologics, but fluid retention/edema is a key on-target liability.	(abraham2023currentandfuture pages 1-4, abraham2023currentandfuture pages 7-11)	Abraham et al. (Dec 2023), https://doi.org/10.17863/cam.104737
Key quantitative data 2023-2024	2023 mechanistic study reported ~27-fold higher ET3 affinity for Y129F and ~10- to 5-fold increases for E303K across assays; E303K increased ligand-free Ca2+/IP1 signaling; in PAH, bosentan-associated peripheral edema occurred in 17% of patients; getagozumab anti-ETA mAb showed Kd ~8.7 nM, IC50 38 nM, and ~21-day first-in-human half-life; rs9349379 minor G allele frequency ~40% in population data.	(kurihara2023mandibulofacialdysostosiswith pages 4-5, abraham2023currentandfuture pages 1-4, abraham2023currentandfuture pages 4-7, abraham2023currentandfuture pages 7-11)	Kurihara et al., J Clin Invest (Feb 2023), https://doi.org/10.1172/jci151536; Abraham et al. (Dec 2023), https://doi.org/10.17863/cam.104737
2024 systems/omics relevance	EDNRA was profiled as a vascular index protein in cell-type-specific IP-MS interaction mapping in human aortic endothelial and coronary artery smooth muscle cells, supporting its placement in arterial-wall disease networks; 2024 review literature also links anti-ETAR autoantibodies to severe vasculopathic manifestations in systemic sclerosis.	(zhu2024proteininteractionnetworks pages 1-2, binda2024autoantibodiestargetinggproteincoupled pages 1-2)	Zhu et al., Commun Biol (Jan 2024), https://doi.org/10.1038/s42003-023-05705-1; Binda et al., Int J Mol Sci (Feb 2024), https://doi.org/10.3390/ijms25042299

Table: This table summarizes evidence-supported functional annotation for mouse Ednra/ETAR, including core molecular function, signaling, localization, developmental roles, translational pharmacology, and recent quantitative findings from 2023-2024 sources.

9) Limitations and evidence gaps (for annotation confidence)

The retrieved 2024 omics paper establishes EDNRA’s inclusion in vascular PPI mapping but the provided pages do not list EDNRA-specific interactors or quantitative interaction strengths; full-text sections containing EDNRA network details would strengthen “protein interaction” annotation. (zhu2024proteininteractionnetworks pages 1-2)
The evidence set is strong for core GPCR function, vascular smooth muscle localization, renal functional relevance, and craniofacial developmental roles, but less complete for a comprehensive mouse tissue atlas (e.g., cell-type-resolved scRNA-seq expression for Ednra in 2023–2024). (abraham2023currentandfuture pages 4-7, zhu2024proteininteractionnetworks pages 1-2)

References

(kurihara2023mandibulofacialdysostosiswith pages 1-2): Yukiko Kurihara, Toru Ekimoto, Christopher T. Gordon, Yasunobu Uchijima, Ryo Sugiyama, Taro Kitazawa, Akiyasu Iwase, Risa Kotani, Rieko Asai, Véronique Pingault, Mitsunori Ikeguchi, Jeanne Amiel, and Hiroki Kurihara. Mandibulofacial dysostosis with alopecia results from etar gain-of-function mutations via allosteric effects on ligand binding. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci151536, doi:10.1172/jci151536. This article has 3 citations and is from a highest quality peer-reviewed journal.
(kurihara2023mandibulofacialdysostosiswith pages 2-3): Yukiko Kurihara, Toru Ekimoto, Christopher T. Gordon, Yasunobu Uchijima, Ryo Sugiyama, Taro Kitazawa, Akiyasu Iwase, Risa Kotani, Rieko Asai, Véronique Pingault, Mitsunori Ikeguchi, Jeanne Amiel, and Hiroki Kurihara. Mandibulofacial dysostosis with alopecia results from etar gain-of-function mutations via allosteric effects on ligand binding. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci151536, doi:10.1172/jci151536. This article has 3 citations and is from a highest quality peer-reviewed journal.
(abraham2023currentandfuture pages 1-4): George R. Abraham, Thomas L. Williams, J. Maguire, Peter J. Greasley, Philip Ambery, and A. Davenport. Current and future strategies for targeting the endothelin pathway in cardiovascular disease. JournalArticle, Dec 2023. URL: https://doi.org/10.17863/cam.104737, doi:10.17863/cam.104737. This article has 25 citations.
(abraham2023currentandfuture pages 39-46): George R. Abraham, Thomas L. Williams, J. Maguire, Peter J. Greasley, Philip Ambery, and A. Davenport. Current and future strategies for targeting the endothelin pathway in cardiovascular disease. JournalArticle, Dec 2023. URL: https://doi.org/10.17863/cam.104737, doi:10.17863/cam.104737. This article has 25 citations.
(seto2024invitroinduction pages 9-10): Yusuke Seto, Ryoma Ogihara, Kaori Takizawa, and Mototsugu Eiraku. In vitro induction of patterned branchial arch-like aggregate from human pluripotent stem cells. Nature Communications, Feb 2024. URL: https://doi.org/10.1038/s41467-024-45285-0, doi:10.1038/s41467-024-45285-0. This article has 8 citations and is from a highest quality peer-reviewed journal.
(kurihara2023mandibulofacialdysostosiswith pages 4-5): Yukiko Kurihara, Toru Ekimoto, Christopher T. Gordon, Yasunobu Uchijima, Ryo Sugiyama, Taro Kitazawa, Akiyasu Iwase, Risa Kotani, Rieko Asai, Véronique Pingault, Mitsunori Ikeguchi, Jeanne Amiel, and Hiroki Kurihara. Mandibulofacial dysostosis with alopecia results from etar gain-of-function mutations via allosteric effects on ligand binding. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci151536, doi:10.1172/jci151536. This article has 3 citations and is from a highest quality peer-reviewed journal.
(abraham2023currentandfuture pages 4-7): George R. Abraham, Thomas L. Williams, J. Maguire, Peter J. Greasley, Philip Ambery, and A. Davenport. Current and future strategies for targeting the endothelin pathway in cardiovascular disease. JournalArticle, Dec 2023. URL: https://doi.org/10.17863/cam.104737, doi:10.17863/cam.104737. This article has 25 citations.
(gyamfi2024thestructuraland pages 48-51): M Adu Gyamfi. The structural and functional activation of endothelin-1 type a receptors (etar). Unknown journal, 2024.
(gyamfi2024thestructuraland pages 54-58): M Adu Gyamfi. The structural and functional activation of endothelin-1 type a receptors (etar). Unknown journal, 2024.
(kurihara2023mandibulofacialdysostosiswith pages 8-11): Yukiko Kurihara, Toru Ekimoto, Christopher T. Gordon, Yasunobu Uchijima, Ryo Sugiyama, Taro Kitazawa, Akiyasu Iwase, Risa Kotani, Rieko Asai, Véronique Pingault, Mitsunori Ikeguchi, Jeanne Amiel, and Hiroki Kurihara. Mandibulofacial dysostosis with alopecia results from etar gain-of-function mutations via allosteric effects on ligand binding. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci151536, doi:10.1172/jci151536. This article has 3 citations and is from a highest quality peer-reviewed journal.
(kurihara2023mandibulofacialdysostosiswith media 5cc1a389): Yukiko Kurihara, Toru Ekimoto, Christopher T. Gordon, Yasunobu Uchijima, Ryo Sugiyama, Taro Kitazawa, Akiyasu Iwase, Risa Kotani, Rieko Asai, Véronique Pingault, Mitsunori Ikeguchi, Jeanne Amiel, and Hiroki Kurihara. Mandibulofacial dysostosis with alopecia results from etar gain-of-function mutations via allosteric effects on ligand binding. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci151536, doi:10.1172/jci151536. This article has 3 citations and is from a highest quality peer-reviewed journal.
(kurihara2023mandibulofacialdysostosiswith media 2cece4c7): Yukiko Kurihara, Toru Ekimoto, Christopher T. Gordon, Yasunobu Uchijima, Ryo Sugiyama, Taro Kitazawa, Akiyasu Iwase, Risa Kotani, Rieko Asai, Véronique Pingault, Mitsunori Ikeguchi, Jeanne Amiel, and Hiroki Kurihara. Mandibulofacial dysostosis with alopecia results from etar gain-of-function mutations via allosteric effects on ligand binding. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci151536, doi:10.1172/jci151536. This article has 3 citations and is from a highest quality peer-reviewed journal.
(kurihara2023mandibulofacialdysostosiswith media 00ca822b): Yukiko Kurihara, Toru Ekimoto, Christopher T. Gordon, Yasunobu Uchijima, Ryo Sugiyama, Taro Kitazawa, Akiyasu Iwase, Risa Kotani, Rieko Asai, Véronique Pingault, Mitsunori Ikeguchi, Jeanne Amiel, and Hiroki Kurihara. Mandibulofacial dysostosis with alopecia results from etar gain-of-function mutations via allosteric effects on ligand binding. Journal of Clinical Investigation, Feb 2023. URL: https://doi.org/10.1172/jci151536, doi:10.1172/jci151536. This article has 3 citations and is from a highest quality peer-reviewed journal.
(zhu2024proteininteractionnetworks pages 1-2): Qiuyu Martin Zhu, Yu-Han H. Hsu, Frederik H. Lassen, Bryan T. MacDonald, Stephanie Stead, Edyta Malolepsza, April Kim, Taibo Li, Taiji Mizoguchi, Monica Schenone, Gaelen Guzman, Benjamin Tanenbaum, Nadine Fornelos, Steven A. Carr, Rajat M. Gupta, Patrick T. Ellinor, and Kasper Lage. Protein interaction networks in the vasculature prioritize genes and pathways underlying coronary artery disease. Communications Biology, Jan 2024. URL: https://doi.org/10.1038/s42003-023-05705-1, doi:10.1038/s42003-023-05705-1. This article has 16 citations and is from a peer-reviewed journal.
(binda2024autoantibodiestargetinggproteincoupled pages 1-2): Marco Binda, Beatrice Moccaldi, Giovanni Civieri, Anna Cuberli, Andrea Doria, Francesco Tona, and Elisabetta Zanatta. Autoantibodies targeting g-protein-coupled receptors: pathogenetic, clinical and therapeutic implications in systemic sclerosis. International Journal of Molecular Sciences, 25:2299, Feb 2024. URL: https://doi.org/10.3390/ijms25042299, doi:10.3390/ijms25042299. This article has 9 citations.
(gyamfi2024thestructuralanda pages 54-58): M Adu Gyamfi. The structural and functional activation of endothelin-1 type a receptors (etar). Unknown journal, 2024.
(abraham2023currentandfuture pages 7-11): George R. Abraham, Thomas L. Williams, J. Maguire, Peter J. Greasley, Philip Ambery, and A. Davenport. Current and future strategies for targeting the endothelin pathway in cardiovascular disease. JournalArticle, Dec 2023. URL: https://doi.org/10.17863/cam.104737, doi:10.17863/cam.104737. This article has 25 citations.

Citations

abraham2023currentandfuture pages 39-46
abraham2023currentandfuture pages 4-7
kurihara2023mandibulofacialdysostosiswith pages 1-2
kurihara2023mandibulofacialdysostosiswith pages 4-5
seto2024invitroinduction pages 9-10
zhu2024proteininteractionnetworks pages 1-2
binda2024autoantibodiestargetinggproteincoupled pages 1-2
abraham2023currentandfuture pages 1-4
abraham2023currentandfuture pages 7-11
kurihara2023mandibulofacialdysostosiswith pages 2-3
gyamfi2024thestructuraland pages 48-51
gyamfi2024thestructuraland pages 54-58
kurihara2023mandibulofacialdysostosiswith pages 8-11
gyamfi2024thestructuralanda pages 54-58
https://doi.org/10.1172/jci151536
https://doi.org/10.1038/s41467-024-45285-0
https://doi.org/10.1038/s42003-023-05705-1
https://doi.org/10.3390/ijms25042299
https://doi.org/10.17863/cam.104737
https://doi.org/10.1172/jci151536;
https://doi.org/10.17863/cam.104737;
https://doi.org/10.1038/s42003-023-05705-1;
https://doi.org/10.1172/jci151536,
https://doi.org/10.17863/cam.104737,
https://doi.org/10.1038/s41467-024-45285-0,
https://doi.org/10.1038/s42003-023-05705-1,
https://doi.org/10.3390/ijms25042299,

Notes

(Ednra-notes.md)

Ednra curation notes

Evidence synthesis

Core receptor identity: Ednra encodes endothelin receptor type A, a seven-transmembrane G protein-coupled receptor. UniProt states that EDNRA is a "Receptor for endothelin-1" that mediates action "by association with G proteins that activate a phosphatidylinositol-calcium second messenger system." [file:mouse/Ednra/Ednra-uniprot.txt]
Core receptor/signaling evidence: Mouse Ednra knockout and antagonist studies place endothelin-A receptor signaling in neural-crest and cardiovascular development. Clouthier et al. report that ETA receptor mRNA is expressed in neural crest-derived ectomesenchyme and that ET-1 ligand is expressed by surrounding arch tissues, supporting a paracrine Edn1-Ednra signaling pathway. [PMID:9449664 "Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice.", "ETA receptor mRNA is expressed by the neural crest-derived ectomesenchymal cells of pharyngeal arches and cardiac outflow tissues"]
Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral axis patterning of pharyngeal arches is regulated by the Ednra-selective, G(q)/G(11)-dependent signaling." This supports Ednra-mediated GPCR signaling, phospholipase/calcium pathway terms, and pharyngeal arch patterning, but not unrelated endothelin receptor family phenotypes. [PMID:18199583 "Recombinase-mediated cassette exchange reveals the selective use of Gq/G11-dependent and -independent endothelin 1/endothelin type A receptor signaling in pharyngeal arch development.", "regulated by the Ednra-selective, G(q)/G(11)-dependent signaling"]
Craniofacial timing and identity: Neural crest-specific deletion and antagonist experiments show Ednra function is required between E8.25 and E9.0 for cranial neural crest patterning, with defects including homeotic transformation of lower jaw structures. This supports face, head, mandibular/maxillary identity, middle-ear, and cranial skeletal annotations as non-core developmental roles. [PMID:19185569 "Elucidating timing and function of endothelin-A receptor signaling during craniofacial development using neural crest cell-specific gene deletion and receptor antagonism.", "Ednra function is crucial for NCC development between E8.25 and E9.0"]
Endothelin switch: Constitutive activation of Ednra "induced the transformation of upper jaw, maxillary, structures into lower jaw, mandibular, structures" and the authors conclude that Edn1/Ednra signaling is responsible for maxillomandibular identity choice. [PMID:19017795 "An endothelin-1 switch specifies maxillomandibular identity.", "Constitutive activation of Ednra induced the transformation of upper jaw, maxillary, structures into lower jaw, mandibular, structures"]
Cardiac neural crest and sympathetic axon evidence: Ednra signaling activates Cdc42 to control cardiac neural crest migration in the outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic axons. These support specific neural crest migration and sympathetic axon guidance terms but do not make general neuron remodeling or heart process terms core. [PMID:31219639 "Cdc42 activation by endothelin regulates neural crest cell migration in the cardiac outflow tract.", "Cdc42 is part of the signaling pathway activated by endothelin specifically in OFT CNCC to control their migration"] [PMID:24875861 "Venous endothelin guides sympathetic innervation of the developing mouse heart.", "venous endothelium-derived endothelin-1, acting through its specific receptor Ednra"]
Vascular tone and blood pressure: Smooth-muscle Ednra signaling contributes to vascular tone; age-dependent hypertension is normalized by ETA blockade and smooth-muscle Ednra inactivation. This supports vasoconstriction and blood-pressure annotations as non-core physiological outputs of EDNRA receptor signaling. [PMID:26531127 "Age-dependent blood pressure elevation is due to increased vascular smooth muscle tone mediated by G-protein signalling.", "Age-dependent hypertension could be normalized by ETA receptor blockade, smooth muscle-specific inactivation of the gene encoding the ETA receptor"]
Renal/podocyte disease-model evidence: Podocyte endothelin receptor signaling elicits calcium transients and contributes to glomerulosclerosis; glomerular endothelial surface layer injury can be prevented by ETA antagonism. These annotations are direct in kidney disease contexts but are not core receptor function. [PMID:24722437 "Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis.", "elicited rapid calcium transients mediated by endothelin type A receptors"] [PMID:31402170 "Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells.", "prevented by endothelin receptor-A antagonism"]
Curation judgment: developmental pigmentation and enteric nervous system development are better-known EDNRB/EDN3-axis phenotypes and are not supported by the mouse Ednra evidence reviewed here. Treat them as paralog/family over-transfer for Ednra unless direct Ednra evidence is found.
Falcon integration: the Falcon report reinforces Ednra as the ETA/endothelin receptor type A class A GPCR, the principal receptor for ET-1-driven vascular smooth muscle vasoconstriction and a receptor for EDN1 in pharyngeal arch neural crest patterning. It specifically supports endothelin peptide receptor activity, plasma-membrane GPCR localization, endothelin receptor signaling, Gq/11-calcium/ERK signaling, vasoconstriction, and mandibular identity roles. [file:mouse/Ednra/Ednra-deep-research-falcon.md "peptide hormone receptor GPCR"; "principal receptor mediating ET-1-driven vasoconstriction"]

📄 View Raw YAML

id: Q61614
gene_symbol: Ednra
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: 'Ednra encodes endothelin receptor type A, a plasma-membrane class A
  GPCR that binds endothelins, especially endothelin-1, and signals through G proteins
  to phosphatidylinositol-calcium, Rho/Cdc42, ERK, and related pathways. Its best-supported
  mouse roles are vasoconstrictive endothelin signaling and Edn1-dependent cranial/cardiac
  neural crest patterning.'
existing_annotations:
- term:
    id: GO:0048066
    label: developmental pigmentation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: developmental pigmentation is not supported as an appropriate
      annotation for Ednra after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a
      paralog/family overreach, or a localization/process inconsistent with the
      curated Ednra biology.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0086100
    label: endothelin receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: endothelin receptor signaling pathway is biologically consistent
      with the curated synthesis for Ednra and is supported by IBA evidence
      (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes EDNRA as transducing endothelin signals
        through heterotrimeric G proteins, especially Gq/11-calcium and ERK
        signaling.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: plasma membrane is biologically consistent with the curated
      synthesis for Ednra and is supported by IBA evidence (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA as a 7-transmembrane class A GPCR
        functioning at the plasma membrane of target cells.
- term:
    id: GO:0004962
    label: endothelin receptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: endothelin receptor activity is biologically consistent with the
      curated synthesis for Ednra and is supported by IBA evidence
      (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA/ETA as an endothelin peptide
        receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the
        canonical receptor state.
- term:
    id: GO:0042310
    label: vasoconstriction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: vasoconstriction is biologically consistent with the curated
      synthesis for Ednra and is supported by IBA evidence (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes ETA/EDNRA as the principal receptor
        mediating ET-1-driven vascular smooth muscle vasoconstriction.
- term:
    id: GO:0004930
    label: G protein-coupled receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: G protein-coupled receptor activity captures the right general
      biology for Ednra, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than endothelin
      receptor activity for this gene. Replace with endothelin receptor activity
      to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0004962
      label: endothelin receptor activity
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
- term:
    id: GO:0004962
    label: endothelin receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: endothelin receptor activity is biologically consistent with the
      curated synthesis for Ednra and is supported by IEA evidence
      (GO_REF:0000120).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA/ETA as an endothelin peptide
        receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the
        canonical receptor state.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: plasma membrane is biologically consistent with the curated
      synthesis for Ednra and is supported by IEA evidence (GO_REF:0000120).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA as a 7-transmembrane class A GPCR
        functioning at the plasma membrane of target cells.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: signal transduction captures the right general biology for Ednra,
      but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than endothelin
      receptor signaling pathway for this gene. Replace with endothelin receptor
      signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0086100
      label: endothelin receptor signaling pathway
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: G protein-coupled receptor signaling pathway captures the right
      general biology for Ednra, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than endothelin
      receptor signaling pathway for this gene. Replace with endothelin receptor
      signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0086100
      label: endothelin receptor signaling pathway
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0008015
    label: blood circulation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: blood circulation is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: regulation of blood pressure is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: membrane is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
- term:
    id: GO:0030202
    label: heparin proteoglycan metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: heparin proteoglycan metabolic process is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0042310
    label: vasoconstriction
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: vasoconstriction is biologically consistent with the curated
      synthesis for Ednra and is supported by IEA evidence (GO_REF:0000120).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes ETA/EDNRA as the principal receptor
        mediating ET-1-driven vascular smooth muscle vasoconstriction.
- term:
    id: GO:0043123
    label: positive regulation of canonical NF-kappaB signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: positive regulation of canonical NF-kappaB signal transduction is
      related to reported Ednra biology only as a broad downstream readout or
      generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0048484
    label: enteric nervous system development
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: enteric nervous system development is not supported as an
      appropriate annotation for Ednra after review of the available mouse
      evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a
      paralog/family overreach, or a localization/process inconsistent with the
      curated Ednra biology.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0055078
    label: sodium ion homeostasis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: sodium ion homeostasis is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0061028
    label: establishment of endothelial barrier
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: establishment of endothelial barrier is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0070294
    label: renal sodium ion absorption
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: renal sodium ion absorption is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0071806
    label: protein transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: protein transmembrane transport is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0072112
    label: podocyte differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: podocyte differentiation is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0097018
    label: renal albumin absorption
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: renal albumin absorption is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0006874
    label: intracellular calcium ion homeostasis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: intracellular calcium ion homeostasis is too broad relative to the
      more specific EDNRA calcium-signaling annotations retained elsewhere.
    action: MARK_AS_OVER_ANNOTATED
    reason: EDNRA-dependent PLC/calcium signaling is better captured by the
      specific cytosolic-calcium and podocyte calcium annotations than by this
      broad homeostasis term.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
- term:
    id: GO:0014824
    label: artery smooth muscle contraction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: artery smooth muscle contraction is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0141156
    label: cAMP/PKA signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cAMP/PKA signal transduction is supported in a DRG pain-sensitization
      context but is not the core EDNRA receptor function.
    action: KEEP_AS_NON_CORE
    reason: PMID:30990108 supports ETAR-PKA-mediated TRPA1 sensitization; this
      is a context-specific nociceptive signaling branch rather than the central
      endothelin receptor/PLC/calcium pathway.
    supported_by:
    - reference_id: PMID:30990108
      supporting_text: ET-1-induced sensitization of TRPA1 in vitro requires
        ETAR-mediated PKA signaling pathway.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: plasma membrane is biologically consistent with the curated
      synthesis for Ednra and is supported by ISO evidence (GO_REF:0000119).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA as a 7-transmembrane class A GPCR
        functioning at the plasma membrane of target cells.
- term:
    id: GO:0001934
    label: positive regulation of protein phosphorylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of protein phosphorylation is related to
      reported Ednra biology only as a broad downstream readout or generic
      interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0001821
    label: histamine secretion
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: histamine secretion is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0003094
    label: glomerular filtration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: glomerular filtration is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0004962
    label: endothelin receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: endothelin receptor activity is biologically consistent with the
      curated synthesis for Ednra and is supported by ISO evidence
      (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA/ETA as an endothelin peptide
        receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the
        canonical receptor state.
- term:
    id: GO:0007200
    label: phospholipase C-activating G protein-coupled receptor signaling
      pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: phospholipase C-activating G protein-coupled receptor signaling
      pathway is a specific supported branch of EDNRA signaling.
    action: ACCEPT
    reason: EDNRA is an endothelin GPCR whose reviewed evidence explicitly
      supports Gq/G11-dependent PLC/phosphatidylinositol-calcium signaling, so
      this mechanistic pathway term should be retained.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
- term:
    id: GO:0007204
    label: positive regulation of cytosolic calcium ion concentration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cytosolic calcium ion concentration is
      biologically consistent with the curated synthesis for Ednra and is
      supported by ISO evidence (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon reports that EDNRA Gq/11 coupling increases
        intracellular calcium and activates ERK phosphorylation.
- term:
    id: GO:0007266
    label: Rho protein signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Rho protein signal transduction is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cell population proliferation is related to
      reported Ednra biology only as a broad downstream readout or generic
      interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0014824
    label: artery smooth muscle contraction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: artery smooth muscle contraction is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0030315
    label: T-tubule
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: T-tubule is not supported as an appropriate annotation for Ednra
      after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a
      paralog/family overreach, or a localization/process inconsistent with the
      curated Ednra biology.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: nuclear membrane is not supported as an appropriate annotation for
      Ednra after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a
      paralog/family overreach, or a localization/process inconsistent with the
      curated Ednra biology.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0032496
    label: response to lipopolysaccharide
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: response to lipopolysaccharide is related to reported Ednra biology
      only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0042310
    label: vasoconstriction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: vasoconstriction is biologically consistent with the curated
      synthesis for Ednra and is supported by ISO evidence (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes ETA/EDNRA as the principal receptor
        mediating ET-1-driven vascular smooth muscle vasoconstriction.
- term:
    id: GO:0042310
    label: vasoconstriction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: vasoconstriction is biologically consistent with the curated
      synthesis for Ednra and is supported by ISO evidence (GO_REF:0000119).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes ETA/EDNRA as the principal receptor
        mediating ET-1-driven vascular smooth muscle vasoconstriction.
- term:
    id: GO:0042482
    label: positive regulation of odontogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of odontogenesis is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0043066
    label: negative regulation of apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of apoptotic process is related to reported
      Ednra biology only as a broad downstream readout or generic interaction
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0048144
    label: fibroblast proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: fibroblast proliferation is related to reported Ednra biology only
      as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0048659
    label: smooth muscle cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: smooth muscle cell proliferation is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0050678
    label: regulation of epithelial cell proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of epithelial cell proliferation is related to reported
      Ednra biology only as a broad downstream readout or generic interaction
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0051281
    label: positive regulation of release of sequestered calcium ion into
      cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of release of sequestered calcium ion into
      cytosol is biologically consistent with the curated synthesis for Ednra
      and is supported by ISO evidence (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
- term:
    id: GO:0051928
    label: positive regulation of calcium ion transport
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of calcium ion transport is biologically
      consistent with the curated synthesis for Ednra and is supported by ISO
      evidence (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
- term:
    id: GO:0070374
    label: positive regulation of ERK1 and ERK2 cascade
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of ERK1 and ERK2 cascade is related to reported
      Ednra biology only as a broad downstream readout or generic interaction
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0071260
    label: cellular response to mechanical stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to mechanical stimulus is related to reported
      Ednra biology only as a broad downstream readout or generic interaction
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0090023
    label: positive regulation of neutrophil chemotaxis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of neutrophil chemotaxis is related to reported
      Ednra biology only as a broad downstream readout or generic interaction
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0090184
    label: positive regulation of kidney development
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of kidney development is related to reported
      Ednra biology only as a broad downstream readout or generic interaction
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0004962
    label: endothelin receptor activity
  evidence_type: IMP
  original_reference_id: PMID:24722437
  review:
    summary: endothelin receptor activity is biologically consistent with the
      curated synthesis for Ednra and is supported by IMP evidence
      (PMID:24722437).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA/ETA as an endothelin peptide
        receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the
        canonical receptor state.
- term:
    id: GO:0086100
    label: endothelin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24722437
  review:
    summary: endothelin receptor signaling pathway is biologically consistent
      with the curated synthesis for Ednra and is supported by IMP evidence
      (PMID:24722437).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes EDNRA as transducing endothelin signals
        through heterotrimeric G proteins, especially Gq/11-calcium and ERK
        signaling.
- term:
    id: GO:0003015
    label: heart process
  evidence_type: IMP
  original_reference_id: PMID:25197047
  review:
    summary: heart process is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0003015
    label: heart process
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: heart process is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0007411
    label: axon guidance
  evidence_type: IMP
  original_reference_id: PMID:30735130
  review:
    summary: axon guidance is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0035904
    label: aorta development
  evidence_type: IMP
  original_reference_id: PMID:14585980
  review:
    summary: aorta development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0002027
    label: regulation of heart rate
  evidence_type: IMP
  original_reference_id: PMID:16399858
  review:
    summary: regulation of heart rate is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0002027
    label: regulation of heart rate
  evidence_type: IGI
  original_reference_id: PMID:16399858
  review:
    summary: regulation of heart rate is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IMP
  original_reference_id: PMID:16399858
  review:
    summary: regulation of blood pressure is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IGI
  original_reference_id: PMID:16399858
  review:
    summary: regulation of blood pressure is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0007411
    label: axon guidance
  evidence_type: IMP
  original_reference_id: PMID:18401410
  review:
    summary: axon guidance is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0014034
    label: neural crest cell fate commitment
  evidence_type: IMP
  original_reference_id: PMID:17294360
  review:
    summary: neural crest cell fate commitment is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0048675
    label: axon extension
  evidence_type: IMP
  original_reference_id: PMID:18401410
  review:
    summary: axon extension is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0060324
    label: face development
  evidence_type: IDA
  original_reference_id: PMID:18199583
  review:
    summary: face development is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0060324
    label: face development
  evidence_type: IMP
  original_reference_id: PMID:18199583
  review:
    summary: face development is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0097152
    label: mesenchymal cell apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:17294360
  review:
    summary: mesenchymal cell apoptotic process is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:1904888
    label: cranial skeletal system development
  evidence_type: IMP
  original_reference_id: PMID:17294360
  review:
    summary: cranial skeletal system development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:1904888
    label: cranial skeletal system development
  evidence_type: IDA
  original_reference_id: PMID:18199583
  review:
    summary: cranial skeletal system development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:1904888
    label: cranial skeletal system development
  evidence_type: IMP
  original_reference_id: PMID:18199583
  review:
    summary: cranial skeletal system development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0044751
    label: cellular response to human chorionic gonadotropin stimulus
  evidence_type: IDA
  original_reference_id: PMID:19111534
  review:
    summary: cellular response to human chorionic gonadotropin stimulus is
      supported for Ednra in a tissue, developmental, trafficking, or
      disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0044751
    label: cellular response to human chorionic gonadotropin stimulus
  evidence_type: IMP
  original_reference_id: PMID:19111534
  review:
    summary: cellular response to human chorionic gonadotropin stimulus is
      supported for Ednra in a tissue, developmental, trafficking, or
      disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0071372
    label: cellular response to follicle-stimulating hormone stimulus
  evidence_type: IDA
  original_reference_id: PMID:19111534
  review:
    summary: cellular response to follicle-stimulating hormone stimulus is
      supported for Ednra in a tissue, developmental, trafficking, or
      disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0071373
    label: cellular response to luteinizing hormone stimulus
  evidence_type: IDA
  original_reference_id: PMID:19111534
  review:
    summary: cellular response to luteinizing hormone stimulus is supported for
      Ednra in a tissue, developmental, trafficking, or disease-model context,
      but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:1903537
    label: meiotic cell cycle process involved in oocyte maturation
  evidence_type: IMP
  original_reference_id: PMID:19111534
  review:
    summary: meiotic cell cycle process involved in oocyte maturation is
      supported for Ednra in a tissue, developmental, trafficking, or
      disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0000278
    label: mitotic cell cycle
  evidence_type: IMP
  original_reference_id: PMID:20929948
  review:
    summary: mitotic cell cycle is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0003207
    label: cardiac chamber formation
  evidence_type: IMP
  original_reference_id: PMID:20929948
  review:
    summary: cardiac chamber formation is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0003220
    label: left ventricular cardiac muscle tissue morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:20929948
  review:
    summary: left ventricular cardiac muscle tissue morphogenesis is supported
      for Ednra in a tissue, developmental, trafficking, or disease-model
      context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0003228
    label: atrial cardiac muscle tissue development
  evidence_type: IMP
  original_reference_id: PMID:20929948
  review:
    summary: atrial cardiac muscle tissue development is supported for Ednra in
      a tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IGI
  original_reference_id: PMID:18784261
  review:
    summary: regulation of blood pressure is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:20929948
  review:
    summary: gene expression is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0014033
    label: neural crest cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:19185569
  review:
    summary: neural crest cell differentiation is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0035050
    label: embryonic heart tube development
  evidence_type: IMP
  original_reference_id: PMID:20929948
  review:
    summary: embryonic heart tube development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0042474
    label: middle ear morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:19185569
  review:
    summary: middle ear morphogenesis is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0055078
    label: sodium ion homeostasis
  evidence_type: IGI
  original_reference_id: PMID:18784261
  review:
    summary: sodium ion homeostasis is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:1904888
    label: cranial skeletal system development
  evidence_type: IMP
  original_reference_id: PMID:19185569
  review:
    summary: cranial skeletal system development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0001525
    label: angiogenesis
  evidence_type: IGI
  original_reference_id: PMID:24043815
  review:
    summary: angiogenesis is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0001569
    label: branching involved in blood vessel morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:23933587
  review:
    summary: branching involved in blood vessel morphogenesis is supported for
      Ednra in a tissue, developmental, trafficking, or disease-model context,
      but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0014033
    label: neural crest cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:23933587
  review:
    summary: neural crest cell differentiation is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0014034
    label: neural crest cell fate commitment
  evidence_type: IMP
  original_reference_id: PMID:23933587
  review:
    summary: neural crest cell fate commitment is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0061626
    label: pharyngeal arch artery morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:23933587
  review:
    summary: pharyngeal arch artery morphogenesis is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0070294
    label: renal sodium ion absorption
  evidence_type: IMP
  original_reference_id: PMID:23698114
  review:
    summary: renal sodium ion absorption is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0001974
    label: blood vessel remodeling
  evidence_type: IMP
  original_reference_id: PMID:25197047
  review:
    summary: blood vessel remodeling is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0007005
    label: mitochondrion organization
  evidence_type: IDA
  original_reference_id: PMID:27899487
  review:
    summary: mitochondrion organization is related to reported Ednra biology
      only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0007382
    label: specification of segmental identity, maxillary segment
  evidence_type: IMP
  original_reference_id: PMID:19017795
  review:
    summary: specification of segmental identity, maxillary segment is supported
      for Ednra in a tissue, developmental, trafficking, or disease-model
      context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IMP
  original_reference_id: PMID:25197047
  review:
    summary: heart development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IMP
  original_reference_id: PMID:24412386
  review:
    summary: regulation of blood pressure is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0009611
    label: response to wounding
  evidence_type: IMP
  original_reference_id: PMID:25197047
  review:
    summary: response to wounding is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0014033
    label: neural crest cell differentiation
  evidence_type: IGI
  original_reference_id: PMID:28455376
  review:
    summary: neural crest cell differentiation is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0016322
    label: neuron remodeling
  evidence_type: IMP
  original_reference_id: PMID:19017795
  review:
    summary: neuron remodeling is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0030878
    label: thyroid gland development
  evidence_type: IMP
  original_reference_id: PMID:26506449
  review:
    summary: thyroid gland development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0032835
    label: glomerulus development
  evidence_type: IMP
  original_reference_id: PMID:27899487
  review:
    summary: glomerulus development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0034599
    label: cellular response to oxidative stress
  evidence_type: IMP
  original_reference_id: PMID:27899487
  review:
    summary: cellular response to oxidative stress is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0042305
    label: specification of segmental identity, mandibular segment
  evidence_type: IMP
  original_reference_id: PMID:19017795
  review:
    summary: specification of segmental identity, mandibular segment is
      supported for Ednra in a tissue, developmental, trafficking, or
      disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0042415
    label: norepinephrine metabolic process
  evidence_type: IMP
  original_reference_id: PMID:25197047
  review:
    summary: norepinephrine metabolic process is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0048485
    label: sympathetic nervous system development
  evidence_type: IMP
  original_reference_id: PMID:25197047
  review:
    summary: sympathetic nervous system development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0048706
    label: embryonic skeletal system development
  evidence_type: IGI
  original_reference_id: PMID:19017795
  review:
    summary: embryonic skeletal system development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0050905
    label: neuromuscular process
  evidence_type: IMP
  original_reference_id: PMID:19017795
  review:
    summary: neuromuscular process is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0097018
    label: renal albumin absorption
  evidence_type: IMP
  original_reference_id: PMID:27899487
  review:
    summary: renal albumin absorption is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0097084
    label: vascular associated smooth muscle cell development
  evidence_type: IMP
  original_reference_id: PMID:24412386
  review:
    summary: vascular associated smooth muscle cell development is supported for
      Ednra in a tissue, developmental, trafficking, or disease-model context,
      but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:1903210
    label: podocyte apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:27899487
  review:
    summary: podocyte apoptotic process is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0001975
    label: response to amphetamine
  evidence_type: IMP
  original_reference_id: PMID:24875861
  review:
    summary: response to amphetamine is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0003253
    label: cardiac neural crest cell migration involved in outflow tract
      morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: cardiac neural crest cell migration involved in outflow tract
      morphogenesis is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0003357
    label: noradrenergic neuron differentiation
  evidence_type: IMP
  original_reference_id: PMID:24875861
  review:
    summary: noradrenergic neuron differentiation is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: protein phosphorylation is related to reported Ednra biology only
      as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IMP
  original_reference_id: PMID:24875861
  review:
    summary: heart development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IMP
  original_reference_id: PMID:26531127
  review:
    summary: regulation of blood pressure is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:30735130
  review:
    summary: gene expression is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: gene expression is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0031175
    label: neuron projection development
  evidence_type: IMP
  original_reference_id: PMID:24875861
  review:
    summary: neuron projection development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0031175
    label: neuron projection development
  evidence_type: IMP
  original_reference_id: PMID:30735130
  review:
    summary: neuron projection development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0035050
    label: embryonic heart tube development
  evidence_type: IMP
  original_reference_id: PMID:24875861
  review:
    summary: embryonic heart tube development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0035050
    label: embryonic heart tube development
  evidence_type: IMP
  original_reference_id: PMID:30735130
  review:
    summary: embryonic heart tube development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0035050
    label: embryonic heart tube development
  evidence_type: IGI
  original_reference_id: PMID:30735130
  review:
    summary: embryonic heart tube development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0035050
    label: embryonic heart tube development
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: embryonic heart tube development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0035904
    label: aorta development
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: aorta development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0060385
    label: axonogenesis involved in innervation
  evidence_type: IMP
  original_reference_id: PMID:24875861
  review:
    summary: axonogenesis involved in innervation is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0060385
    label: axonogenesis involved in innervation
  evidence_type: IMP
  original_reference_id: PMID:30735130
  review:
    summary: axonogenesis involved in innervation is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0061626
    label: pharyngeal arch artery morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: pharyngeal arch artery morphogenesis is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0071526
    label: semaphorin-plexin signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:30735130
  review:
    summary: semaphorin-plexin signaling pathway is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0086100
    label: endothelin receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: endothelin receptor signaling pathway is biologically consistent
      with the curated synthesis for Ednra and is supported by IMP evidence
      (PMID:31219639).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes EDNRA as transducing endothelin signals
        through heterotrimeric G proteins, especially Gq/11-calcium and ERK
        signaling.
- term:
    id: GO:0097492
    label: sympathetic neuron axon guidance
  evidence_type: IGI
  original_reference_id: PMID:30735130
  review:
    summary: sympathetic neuron axon guidance is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:1905144
    label: response to acetylcholine
  evidence_type: IMP
  original_reference_id: PMID:26531127
  review:
    summary: response to acetylcholine is related to reported Ednra biology only
      as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:1905871
    label: regulation of protein localization to cell leading edge
  evidence_type: IMP
  original_reference_id: PMID:31219639
  review:
    summary: regulation of protein localization to cell leading edge is related
      to reported Ednra biology only as a broad downstream readout or generic
      interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Cardiac neural crest and sympathetic axon evidence: Ednra
        signaling activates Cdc42 to control cardiac neural crest migration in the
        outflow tract, and venous Edn1-Ednra signaling guides cardiac sympathetic
        axons.'
- term:
    id: GO:0003094
    label: glomerular filtration
  evidence_type: IDA
  original_reference_id: PMID:31402170
  review:
    summary: glomerular filtration is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:30990108
  review:
    summary: plasma membrane is biologically consistent with the curated
      synthesis for Ednra and is supported by IDA evidence (PMID:30990108).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA as a 7-transmembrane class A GPCR
        functioning at the plasma membrane of target cells.
- term:
    id: GO:0006874
    label: intracellular calcium ion homeostasis
  evidence_type: ISO
  original_reference_id: PMID:30990108
  review:
    summary: This DRG pain study supports ETAR/TRPA1 sensitization rather than
      a core intracellular calcium homeostasis annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: ET-1 did not induce robust calcium signals in native mouse DRG neurons;
      Ednra calcium signaling is better captured by the more specific retained
      cytosolic-calcium and podocyte calcium annotations.
    supported_by:
    - reference_id: PMID:30990108
      supporting_text: Application of ET-1 (100 nM) did not induce strong Ca2+
        signals in mouse DRG neurons as in HEK293 cells
- term:
    id: GO:0006874
    label: intracellular calcium ion homeostasis
  evidence_type: IMP
  original_reference_id: PMID:30990108
  review:
    summary: This DRG pain study supports ETAR/TRPA1 sensitization rather than
      a core intracellular calcium homeostasis annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: ET-1 did not induce robust calcium signals in native mouse DRG neurons;
      Ednra calcium signaling is better captured by the more specific retained
      cytosolic-calcium and podocyte calcium annotations.
    supported_by:
    - reference_id: PMID:30990108
      supporting_text: Application of ET-1 (100 nM) did not induce strong Ca2+
        signals in mouse DRG neurons as in HEK293 cells
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IGI
  original_reference_id: PMID:24722437
  review:
    summary: gene expression is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0060070
    label: canonical Wnt signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:24722437
  review:
    summary: canonical Wnt signaling pathway is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: treatment with endothelin-1 increased total β-catenin
        and phospho-NF-κB expression in wild-type glomeruli, but this effect was
        attenuated in Pod-ETRKO glomeruli.
- term:
    id: GO:0070301
    label: cellular response to hydrogen peroxide
  evidence_type: ISO
  original_reference_id: PMID:30990108
  review:
    summary: cellular response to hydrogen peroxide is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:30990108
      supporting_text: ET-1 sensitizes TRPA1 channel activated by endogenous agonist
        H2O2
- term:
    id: GO:0070588
    label: calcium ion transmembrane transport
  evidence_type: IDA
  original_reference_id: PMID:24722437
  review:
    summary: calcium ion transmembrane transport is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0070588
    label: calcium ion transmembrane transport
  evidence_type: IMP
  original_reference_id: PMID:24722437
  review:
    summary: calcium ion transmembrane transport is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0070588
    label: calcium ion transmembrane transport
  evidence_type: IGI
  original_reference_id: PMID:24722437
  review:
    summary: calcium ion transmembrane transport is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:24722437
      supporting_text: Stimulation of primary mouse podocytes with endothelin-1
        elicited rapid calcium transients mediated by endothelin type A receptors
        (ETARs) and endothelin type B receptors (ETBRs).
- term:
    id: GO:0072011
    label: glomerular endothelium development
  evidence_type: IDA
  original_reference_id: PMID:31402170
  review:
    summary: glomerular endothelium development is supported for Ednra in a
      tissue, developmental, trafficking, or disease-model context, but it is
      not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0072112
    label: podocyte differentiation
  evidence_type: IDA
  original_reference_id: PMID:31402170
  review:
    summary: podocyte differentiation is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0086100
    label: endothelin receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:24722437
  review:
    summary: endothelin receptor signaling pathway is biologically consistent
      with the curated synthesis for Ednra and is supported by IGI evidence
      (PMID:24722437).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Gq/G11 pathway specificity: Sato et al. report that "the dorsoventral
        axis patterning of pharyngeal arches is regulated by the Ednra-selective,
        G(q)/G(11)-dependent signaling."'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes EDNRA as transducing endothelin signals
        through heterotrimeric G proteins, especially Gq/11-calcium and ERK
        signaling.
- term:
    id: GO:0097018
    label: renal albumin absorption
  evidence_type: IDA
  original_reference_id: PMID:31402170
  review:
    summary: renal albumin absorption is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Renal/podocyte disease-model evidence: Podocyte endothelin
        receptor signaling elicits calcium transients and contributes to glomerulosclerosis;
        glomerular endothelial surface layer injury can be prevented by ETA antagonism.'
- term:
    id: GO:0097237
    label: cellular response to toxic substance
  evidence_type: ISO
  original_reference_id: PMID:30990108
  review:
    summary: cellular response to toxic substance is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0097237
    label: cellular response to toxic substance
  evidence_type: IDA
  original_reference_id: PMID:30990108
  review:
    summary: cellular response to toxic substance is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0097237
    label: cellular response to toxic substance
  evidence_type: IMP
  original_reference_id: PMID:30990108
  review:
    summary: cellular response to toxic substance is related to reported Ednra
      biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0141156
    label: cAMP/PKA signal transduction
  evidence_type: ISO
  original_reference_id: PMID:30990108
  review:
    summary: cAMP/PKA signal transduction is supported in a DRG pain-sensitization
      context but is not the core EDNRA receptor function.
    action: KEEP_AS_NON_CORE
    reason: PMID:30990108 supports ETAR-PKA-mediated TRPA1 sensitization; this
      is a context-specific nociceptive signaling branch rather than the central
      endothelin receptor/PLC/calcium pathway.
    supported_by:
    - reference_id: PMID:30990108
      supporting_text: ET-1-induced sensitization of TRPA1 in vitro requires
        ETAR-mediated PKA signaling pathway.
- term:
    id: GO:2001259
    label: positive regulation of cation channel activity
  evidence_type: ISO
  original_reference_id: PMID:30990108
  review:
    summary: positive regulation of cation channel activity is supported in a
      DRG TRPA1 sensitization context but is not core EDNRA receptor identity.
    action: KEEP_AS_NON_CORE
    reason: PMID:30990108 directly supports ETAR-dependent TRPA1 channel
      sensitization as a pain-specific signaling output, so the term is retained
      as non-core rather than treated as the primary receptor function.
    supported_by:
    - reference_id: PMID:30990108
      supporting_text: ET-1 sensitizes TRPA1 channel activated by endogenous agonist
        H2O2
- term:
    id: GO:0007193
    label: adenylate cyclase-inhibiting G protein-coupled receptor signaling
      pathway
  evidence_type: IGI
  original_reference_id: PMID:15928212
  review:
    summary: adenylate cyclase-inhibiting G protein-coupled receptor signaling
      pathway is related to reported Ednra biology only as a broad downstream
      readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0010827
    label: regulation of D-glucose transmembrane transport
  evidence_type: IDA
  original_reference_id: PMID:11546805
  review:
    summary: regulation of D-glucose transmembrane transport is supported for
      Ednra in a tissue, developmental, trafficking, or disease-model context,
      but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0060322
    label: head development
  evidence_type: IMP
  original_reference_id: PMID:15306564
  review:
    summary: head development is supported for Ednra in a tissue, developmental,
      trafficking, or disease-model context, but it is not the core molecular
      role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0014032
    label: neural crest cell development
  evidence_type: IMP
  original_reference_id: PMID:15306564
  review:
    summary: neural crest cell development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11546805
  review:
    summary: protein binding is not supported as an appropriate annotation for
      Ednra after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a
      paralog/family overreach, or a localization/process inconsistent with the
      curated Ednra biology.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0001666
    label: response to hypoxia
  evidence_type: IMP
  original_reference_id: PMID:9449664
  review:
    summary: response to hypoxia is related to reported Ednra biology only as a
      broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated
      model is better captured by the specific receptor/ligand, pathway, and
      supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0001701
    label: in utero embryonic development
  evidence_type: IMP
  original_reference_id: PMID:15327783
  review:
    summary: in utero embryonic development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0004962
    label: endothelin receptor activity
  evidence_type: IMP
  original_reference_id: PMID:9449664
  review:
    summary: endothelin receptor activity is biologically consistent with the
      curated synthesis for Ednra and is supported by IMP evidence
      (PMID:9449664).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon identifies EDNRA/ETA as an endothelin peptide
        receptor GPCR, with higher affinity for ET1/ET2 than ET3 in the
        canonical receptor state.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9449664
  review:
    summary: protein binding is not supported as an appropriate annotation for
      Ednra after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a
      paralog/family overreach, or a localization/process inconsistent with the
      curated Ednra biology.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Curation judgment: developmental pigmentation and enteric
        nervous system development are better-known EDNRB/EDN3-axis phenotypes and
        are not supported by the mouse Ednra evidence reviewed here.'
- term:
    id: GO:0007585
    label: respiratory gaseous exchange by respiratory system
  evidence_type: IMP
  original_reference_id: PMID:9449664
  review:
    summary: respiratory gaseous exchange by respiratory system is supported for
      Ednra in a tissue, developmental, trafficking, or disease-model context,
      but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0014032
    label: neural crest cell development
  evidence_type: IMP
  original_reference_id: PMID:15327783
  review:
    summary: neural crest cell development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0014032
    label: neural crest cell development
  evidence_type: IMP
  original_reference_id: PMID:9449664
  review:
    summary: neural crest cell development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0042310
    label: vasoconstriction
  evidence_type: IMP
  original_reference_id: PMID:9826706
  review:
    summary: vasoconstriction is biologically consistent with the curated
      synthesis for Ednra and is supported by IMP evidence (PMID:9826706).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or
      location/physiological output of Ednra; it is specific enough to retain
      without replacement.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Vascular tone and blood pressure: Smooth-muscle Ednra signaling
        contributes to vascular tone; age-dependent hypertension is normalized by
        ETA blockade and smooth-muscle Ednra inactivation.'
    - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
      supporting_text: Falcon describes ETA/EDNRA as the principal receptor
        mediating ET-1-driven vascular smooth muscle vasoconstriction.
- term:
    id: GO:0001569
    label: branching involved in blood vessel morphogenesis
  evidence_type: IGI
  original_reference_id: PMID:15664398
  review:
    summary: branching involved in blood vessel morphogenesis is supported for
      Ednra in a tissue, developmental, trafficking, or disease-model context,
      but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IGI
  original_reference_id: PMID:15664398
  review:
    summary: heart development is supported for Ednra in a tissue,
      developmental, trafficking, or disease-model context, but it is not the
      core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0007585
    label: respiratory gaseous exchange by respiratory system
  evidence_type: IMP
  original_reference_id: PMID:10626068
  review:
    summary: respiratory gaseous exchange by respiratory system is supported for
      Ednra in a tissue, developmental, trafficking, or disease-model context,
      but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific
      consequence of Ednra activity. It should be retained as non-core so it
      does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
- term:
    id: GO:0004930
    label: G protein-coupled receptor activity
  evidence_type: TAS
  original_reference_id: PMID:11546805
  review:
    summary: G protein-coupled receptor activity captures the right general
      biology for Ednra, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than endothelin
      receptor activity for this gene. Replace with endothelin receptor activity
      to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0004962
      label: endothelin receptor activity
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor
        type A, a seven-transmembrane G protein-coupled receptor.'
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: TAS
  original_reference_id: PMID:11546805
  review:
    summary: G protein-coupled receptor signaling pathway captures the right
      general biology for Ednra, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than endothelin
      receptor signaling pathway for this gene. Replace with endothelin receptor
      signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0086100
      label: endothelin receptor signaling pathway
    supported_by:
    - reference_id: file:mouse/Ednra/Ednra-notes.md
      supporting_text: 'Craniofacial timing and identity: Neural crest-specific deletion
        and antagonist experiments show Ednra function is required between E8.25 and
        E9.0 for cranial neural crest patterning, with defects including homeotic
        transformation of lower jaw structures.'
references:
- id: file:mouse/Ednra/Ednra-notes.md
  title: Curator notes for mouse Ednra review
- id: file:mouse/Ednra/Ednra-deep-research-falcon.md
  title: Falcon deep research report for mouse Ednra
- id: file:mouse/Ednra/Ednra-uniprot.txt
  title: UniProtKB record for mouse Ednra
- id: file:mouse/Ednra/Ednra-goa.tsv
  title: QuickGO export for mouse Ednra
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with
    GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data
    to mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning
    models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data
    to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10626068
  title: Endothelin in the central control of cardiovascular and respiratory
    functions.
  findings: []
- id: PMID:11546805
  title: beta -Arrestin-mediated recruitment of the Src family kinase Yes
    mediates endothelin-1-stimulated glucose transport.
  findings: []
- id: PMID:14585980
  title: Cardiomyocyte-specific endothelin A receptor knockout mice have normal
    cardiac function and an unaltered hypertrophic response to angiotensin II
    and isoproterenol.
  findings: []
- id: PMID:15306564
  title: Endothelin-A receptor-dependent and -independent signaling pathways in
    establishing mandibular identity.
  findings: []
- id: PMID:15327783
  title: Temporal requirement of signaling cascade involving
    endothelin-1/endothelin receptor type A in branchial arch development.
  findings: []
- id: PMID:15664398
  title: Roles of forkhead transcription factor Foxc2 (MFH-1) and endothelin
    receptor A in cardiovascular morphogenesis.
  findings: []
- id: PMID:15928212
  title: Collecting duct-specific knockout of the endothelin A receptor alters
    renal vasopressin responsiveness, but not sodium excretion or blood
    pressure.
  findings: []
- id: PMID:16399858
  title: Blood pressure regulation by ETA and ETB receptors in conscious,
    telemetry-instrumented mice and role of ETA in hypertension produced by
    selective ETB blockade.
  findings: []
- id: PMID:17294360
  title: Fate of cranial neural crest cells during craniofacial development in
    endothelin-A receptor-deficient mice.
  findings: []
- id: PMID:18199583
  title: Recombinase-mediated cassette exchange reveals the selective use of
    Gq/G11-dependent and -independent endothelin 1/endothelin type A receptor
    signaling in pharyngeal arch development.
  findings: []
- id: PMID:18401410
  title: Endothelins are vascular-derived axonal guidance cues for developing
    sympathetic neurons.
  findings: []
- id: PMID:18784261
  title: Combined knockout of collecting duct endothelin A and B receptors
    causes hypertension and sodium retention.
  findings: []
- id: PMID:19017795
  title: An endothelin-1 switch specifies maxillomandibular identity.
  findings: []
- id: PMID:19111534
  title: Paracrine regulation of the resumption of oocyte meiosis by
    endothelin-1.
  findings: []
- id: PMID:19185569
  title: Elucidating timing and function of endothelin-A receptor signaling
    during craniofacial development using neural crest cell-specific gene
    deletion and receptor antagonism.
  findings: []
- id: PMID:20929948
  title: Endothelin receptor type A expression defines a distinct cardiac
    subdomain within the heart field and is later implicated in chamber
    myocardium formation.
  findings: []
- id: PMID:23698114
  title: Endothelin-1 inhibits sodium reabsorption by ET(A) and ET(B) receptors
    in the mouse cortical collecting duct.
  findings: []
- id: PMID:23933587
  title: Endothelin regulates neural crest deployment and fate to form great
    vessels through Dlx5/Dlx6-independent mechanisms.
  findings: []
- id: PMID:24043815
  title: Endothelin-2 signaling in the neural retina promotes the endothelial
    tip cell state and inhibits angiogenesis.
  findings: []
- id: PMID:24412386
  title: Smooth muscle specific disruption of the endothelin-A receptor in mice
    reduces arterial pressure, and vascular reactivity and affects vascular
    development.
  findings: []
- id: PMID:24722437
  title: Direct action of endothelin-1 on podocytes promotes diabetic
    glomerulosclerosis.
  findings: []
- id: PMID:24875861
  title: Venous endothelin guides sympathetic innervation of the developing
    mouse heart.
  findings: []
- id: PMID:25197047
  title: Essential role of sympathetic endothelin A receptors for adverse
    cardiac remodeling.
  findings: []
- id: PMID:26506449
  title: Postotic and preotic cranial neural crest cells differently contribute
    to thyroid development.
  findings: []
- id: PMID:26531127
  title: Age-dependent blood pressure elevation is due to increased vascular
    smooth muscle tone mediated by G-protein signalling.
  findings: []
- id: PMID:27899487
  title: Glomerular Endothelial Mitochondrial Dysfunction Is Essential and
    Characteristic of Diabetic Kidney Disease Susceptibility.
  findings: []
- id: PMID:28455376
  title: Negative regulation of endothelin signaling by SIX1 is required for
    proper maxillary development.
  findings: []
- id: PMID:30735130
  title: Venous endothelin modulates responsiveness of cardiac sympathetic axons
    to arterial semaphorin.
  findings: []
- id: PMID:30990108
  title: 'ET(A)R and protein kinase A pathway mediate ET-1 sensitization of TRPA1
    channel: A molecular mechanism of ET-1-induced mechanical hyperalgesia.'
  findings: []
- id: PMID:31219639
  title: Cdc42 activation by endothelin regulates neural crest cell migration in
    the cardiac outflow tract.
  findings: []
- id: PMID:31402170
  title: Endothelin receptor-A mediates degradation of the glomerular
    endothelial surface layer via pathologic crosstalk between activated
    podocytes and glomerular endothelial cells.
  findings: []
- id: PMID:9449664
  title: Cranial and cardiac neural crest defects in endothelin-A
    receptor-deficient mice.
  findings: []
- id: PMID:9826706
  title: Endothelin ETA receptor blockade restores NO-mediated endothelial
    function and inhibits atherosclerosis in apolipoprotein E-deficient mice.
  findings: []
core_functions:
- description: EDNRA is a plasma-membrane endothelin receptor that activates
    GPCR signaling in response to endothelin ligands, especially ET-1, coupling
    to phosphatidylinositol-calcium and small-GTPase pathways that control
    vasoconstriction and developmental patterning.
  molecular_function:
    id: GO:0004962
    label: endothelin receptor activity
  directly_involved_in:
  - id: GO:0086100
    label: endothelin receptor signaling pathway
  - id: GO:0042310
    label: vasoconstriction
  - id: GO:0007204
    label: positive regulation of cytosolic calcium ion concentration
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: file:mouse/Ednra/Ednra-notes.md
    supporting_text: 'Core receptor identity: Ednra encodes endothelin receptor type
      A, a seven-transmembrane G protein-coupled receptor.'
  - reference_id: file:mouse/Ednra/Ednra-deep-research-falcon.md
    supporting_text: Falcon reinforces the core model that EDNRA is a
      plasma-membrane endothelin peptide GPCR mediating endothelin receptor
      signaling, vasoconstriction, calcium signaling, and mandibular neural
      crest patterning.
proposed_new_terms: []
suggested_questions:
- question: Should GO distinguish endothelin A receptor activity from general
    endothelin receptor activity to avoid conflating EDNRA and EDNRB family
    functions?
suggested_experiments:
- hypothesis: EDNRA developmental functions are mediated by specific Gq/G11 and
    Cdc42 pathway branches rather than generic GPCR signaling.
  description: In cranial/cardiac neural crest models, rescue Ednra loss with
    pathway-selective receptor mutants and assay Dlx/Hand2 expression, Cdc42
    localization, and outflow-tract migration.
  experiment_type: pathway-selective rescue

Ednra

Gene Description

Existing Annotations Review

Core Functions

EDNRA is a plasma-membrane endothelin receptor that activates GPCR signaling in response to endothelin ligands, especially ET-1, coupling to phosphatidylinositol-calcium and small-GTPase pathways that control vasoconstriction and developmental patterning.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Research report: Mouse Ednra (UniProt Q61614) — functional annotation and recent literature (2023–2024 prioritized)

1) Target verification (mandatory)

2) Key concepts and definitions (current understanding)

2.1 Endothelin system overview and EDNRA’s role

2.2 Molecular function (what the protein does)

2.3 Subcellular/cellular localization (where it acts)

2.4 Core signaling pathways downstream of EDNRA

3) Recent developments and latest research (2023–2024)

3.1 2023: Allosteric GPCR mechanisms and craniofacial disease—EDNRA gain-of-function

3.2 2024: Human PSC branchial-arch model recapitulating EDN1–EDNRA jaw patterning logic

3.3 2024: Vascular omics/network placement of EDNRA

3.4 2024: EDNRA as an autoantigen/functional target in systemic sclerosis

4) Current applications and real-world implementations

4.1 Pharmacologic EDNRA targeting: ETA antagonists and beyond

4.2 Developmental biology applications

5) Expert opinions and analysis (authoritative synthesis)

5.1 EDNRA/ETA as a central vasoconstrictor axis

5.2 EDNRA as an instructive developmental signaling receptor

5.3 EDNRA signaling complexity and bias

6) Relevant statistics and data (recent studies)

6.1 Quantitative molecular pharmacology/biophysics (2023)

6.2 Clinical/real-world adverse event rates and drug statistics (2023)

6.3 Quantitative clinical PK/PD for anti-ETA biologic (2023)

6.4 Human population genetics statistics relevant to EDNRA regulation (2023)

7) Practical functional annotation summary (mouse Ednra / Q61614)

8) Evidence summary table

9) Limitations and evidence gaps (for annotation confidence)

Citations

Notes

Ednra curation notes

Evidence synthesis

📄 View Raw YAML