Edn1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006874 intracellular calcium ion homeostasis	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: intracellular calcium ion homeostasis is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
GO:0045987 positive regulation of smooth muscle contraction	IBA GO_REF:0000033	ACCEPT	Summary: positive regulation of smooth muscle contraction is biologically consistent with the curated synthesis for Edn1 and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon identifies ET-1 as a potent vasoconstrictor whose ETA signaling in vascular smooth muscle promotes sustained contraction.
GO:0003100 regulation of systemic arterial blood pressure by endothelin	IBA GO_REF:0000033	ACCEPT	Summary: regulation of systemic arterial blood pressure by endothelin is biologically consistent with the curated synthesis for Edn1 and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes ET-1 as a central regulator of vascular tone and blood pressure through receptor-specific endothelin signaling.
GO:0005179 hormone activity	IBA GO_REF:0000033	ACCEPT	Summary: hormone activity is biologically consistent with the curated synthesis for Edn1 and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon describes Edn1 as encoding a secreted peptide hormone precursor that yields mature endothelin-1, supporting hormone/receptor ligand activity.
GO:0005615 extracellular space	IBA GO_REF:0000033	ACCEPT	Summary: extracellular space is biologically consistent with the curated synthesis for Edn1 and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon states that ET-1 functions as an extracellular ligand produced by endothelial and epithelial cells.
GO:0014826 vein smooth muscle contraction	IBA GO_REF:0000033	ACCEPT	Summary: vein smooth muscle contraction is biologically consistent with the curated synthesis for Edn1 and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0031707 endothelin A receptor binding	IBA GO_REF:0000033	ACCEPT	Summary: endothelin A receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETA/EDNRA receptors, supporting endothelin A receptor binding.
GO:0031708 endothelin B receptor binding	IBA GO_REF:0000033	ACCEPT	Summary: endothelin B receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETB/EDNRB receptors, supporting endothelin B receptor binding.
GO:0005576 extracellular region	IEA GO_REF:0000120	ACCEPT	Summary: extracellular region is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon states that ET-1 functions as an extracellular ligand produced by endothelial and epithelial cells.
GO:0019229 regulation of vasoconstriction	IEA GO_REF:0000002	MODIFY	Summary: regulation of vasoconstriction captures the right general biology for Edn1, but a more specific GO term is available. Reason: The current term is too broad or less precise than vasoconstriction for this gene. Replace with vasoconstriction to align the annotation with the reviewed evidence. Proposed replacements: vasoconstriction Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0042310 vasoconstriction	IEA GO_REF:0000120	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0097746 blood vessel diameter maintenance	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: blood vessel diameter maintenance is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0000122 negative regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: negative regulation of transcription by RNA polymerase II is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0001666 response to hypoxia	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: response to hypoxia is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0001821 histamine secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: histamine secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0003100 regulation of systemic arterial blood pressure by endothelin	IEA GO_REF:0000107	ACCEPT	Summary: regulation of systemic arterial blood pressure by endothelin is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes ET-1 as a central regulator of vascular tone and blood pressure through receptor-specific endothelin signaling.
GO:0005125 cytokine activity	IEA GO_REF:0000107	MODIFY	Summary: cytokine activity captures the right general biology for Edn1, but a more specific GO term is available. Reason: The current term is too broad or less precise than receptor ligand activity for this gene. Replace with receptor ligand activity to align the annotation with the reviewed evidence. Proposed replacements: receptor ligand activity Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB.
GO:0005179 hormone activity	IEA GO_REF:0000107	ACCEPT	Summary: hormone activity is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon describes Edn1 as encoding a secreted peptide hormone precursor that yields mature endothelin-1, supporting hormone/receptor ligand activity.
GO:0005615 extracellular space	IEA GO_REF:0000120	ACCEPT	Summary: extracellular space is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon states that ET-1 functions as an extracellular ligand produced by endothelial and epithelial cells.
GO:0005737 cytoplasm	IEA GO_REF:0000107	REMOVE	Summary: cytoplasm is not supported as an appropriate annotation for Edn1 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 Edn1 biology. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0006874 intracellular calcium ion homeostasis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: intracellular calcium ion homeostasis is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
GO:0007166 cell surface receptor signaling pathway	IEA GO_REF:0000107	MODIFY	Summary: cell surface receptor signaling pathway captures the right general biology for Edn1, 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/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000107	MODIFY	Summary: G protein-coupled receptor signaling pathway captures the right general biology for Edn1, 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/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0007204 positive regulation of cytosolic calcium ion concentration	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of cytosolic calcium ion concentration is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0007267 cell-cell signaling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cell-cell signaling is biologically consistent with secreted paracrine Edn1 ligand activity but is less specific than endothelin receptor signaling. Reason: Edn1 is a secreted peptide ligand that mediates receptor-dependent communication between cells; retain the broad signaling term as non-core while preferring endothelin receptor signaling and receptor ligand terms. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB.
GO:0008217 regulation of blood pressure	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: positive regulation of cell population proliferation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to xenobiotic stimulus is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0010193 response to ozone	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to ozone is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0010460 positive regulation of heart rate	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of heart rate is related to reported Edn1 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: PMID:23933587 Edn1 and Ednra knock-out mice demonstrate abnormalities in pharyngeal arch artery patterning
GO:0010613 positive regulation of cardiac muscle hypertrophy	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of cardiac muscle hypertrophy is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0010629 negative regulation of gene expression	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: negative regulation of gene expression is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0014823 response to activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to activity is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0014824 artery smooth muscle contraction	IEA GO_REF:0000120	ACCEPT	Summary: artery smooth muscle contraction is a direct vascular output of endothelin-1 receptor signaling. Reason: ET-1 is a vasoactive peptide ligand whose ETA/EDNRA signaling in vascular smooth muscle drives vasoconstriction through PLC/calcium signaling, making this term consistent with the curated vascular contraction function. Supporting Evidence: file:mouse/Edn1/Edn1-deep-research-falcon.md ETA (EDNRA/ETAR): classically enriched on vascular smooth muscle cells (VSMCs) and mediates potent, sustained vasoconstriction and growth/remodeling programs.
GO:0014826 vein smooth muscle contraction	IEA GO_REF:0000107	ACCEPT	Summary: vein smooth muscle contraction is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0019722 calcium-mediated signaling	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: calcium-mediated signaling is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0023019 signal transduction involved in regulation of gene expression	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: signal transduction involved in regulation of gene expression is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0030072 peptide hormone secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: peptide hormone secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0030185 nitric oxide transport	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: nitric oxide transport is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0030335 positive regulation of cell migration	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of cell migration is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0031707 endothelin A receptor binding	IEA GO_REF:0000120	ACCEPT	Summary: endothelin A receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETA/EDNRA receptors, supporting endothelin A receptor binding.
GO:0031708 endothelin B receptor binding	IEA GO_REF:0000120	ACCEPT	Summary: endothelin B receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETB/EDNRB receptors, supporting endothelin B receptor binding.
GO:0032308 positive regulation of prostaglandin secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of prostaglandin secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0032496 response to lipopolysaccharide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to lipopolysaccharide is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0033093 Weibel-Palade body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Weibel-Palade body localization reflects endothelial regulated storage/secretion of ET-1 precursor-processing components. Reason: This supports regulated endothelial storage and secretion of ET-1, but remains a localization/trafficking context rather than the core ligand signaling role. Supporting Evidence: file:mouse/Edn1/Edn1-deep-research-falcon.md ET-1 precursors and processing components can be stored in endothelial secretory vesicles, particularly Weibel-Palade bodies, with reported co-localization of pro-ET-1 and ECE-1.
GO:0033574 response to testosterone	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to testosterone is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0034392 negative regulation of smooth muscle cell apoptotic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: negative regulation of smooth muscle cell apoptotic process is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0034696 response to prostaglandin F	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to prostaglandin F is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0035094 response to nicotine	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to nicotine is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0035556 intracellular signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: intracellular signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0035994 response to muscle stretch	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to muscle stretch is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0042045 epithelial fluid transport	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: epithelial fluid transport is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0042482 positive regulation of odontogenesis	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of odontogenesis is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0042554 superoxide anion generation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: superoxide anion generation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0043200 response to amino acid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to amino acid is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0043410 positive regulation of MAPK cascade	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of MAPK cascade is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0044321 response to leptin	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to leptin is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045178 basal part of cell	IEA GO_REF:0000107	UNDECIDED	Summary: The local evidence supports Edn1 as a secreted ligand but does not verify this specific basal-cell localization. Reason: The generic secreted-ligand evidence and Weibel-Palade storage model do not establish a basal part of cell annotation for Edn1.
GO:0045793 positive regulation of cell size	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of cell size is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045840 positive regulation of mitotic nuclear division	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of mitotic nuclear division is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: positive regulation of transcription by RNA polymerase II is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045987 positive regulation of smooth muscle contraction	IEA GO_REF:0000107	ACCEPT	Summary: positive regulation of smooth muscle contraction is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon identifies ET-1 as a potent vasoconstrictor whose ETA signaling in vascular smooth muscle promotes sustained contraction.
GO:0046330 positive regulation of JNK cascade	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of JNK cascade is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0046887 positive regulation of hormone secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of hormone secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0046888 negative regulation of hormone secretion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: negative regulation of hormone secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0048237 rough endoplasmic reticulum lumen	IEA GO_REF:0000107	UNDECIDED	Summary: The local evidence supports Edn1 as a secreted peptide precursor, but does not verify a rough endoplasmic reticulum lumen localization. Reason: Secretory-protein biology alone is not enough to retain this specific automated cellular-component annotation without direct localization evidence.
GO:0048661 positive regulation of smooth muscle cell proliferation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of smooth muscle cell proliferation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0050850 positive regulation of calcium-mediated signaling	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of calcium-mediated signaling is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0051248 negative regulation of protein metabolic process	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: negative regulation of protein metabolic process is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0051899 membrane depolarization	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: membrane depolarization is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0060137 maternal process involved in parturition	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: maternal process involved in parturition is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0060298 positive regulation of sarcomere organization	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of sarcomere organization is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of cell growth involved in cardiac muscle cell development is related to reported Edn1 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: PMID:23933587 Edn1/Ednra signaling is involved in pharyngeal artery development by controlling the fate of neural crest cells
GO:0070301 cellular response to hydrogen peroxide	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to hydrogen peroxide is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071277 cellular response to calcium ion	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to calcium ion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071346 cellular response to type II interferon	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to type II interferon is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071347 cellular response to interleukin-1	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to interleukin-1 is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071356 cellular response to tumor necrosis factor	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to tumor necrosis factor is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071375 cellular response to peptide hormone stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to peptide hormone stimulus is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071385 cellular response to glucocorticoid stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to glucocorticoid stimulus is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071389 cellular response to mineralocorticoid stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to mineralocorticoid stimulus is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071398 cellular response to fatty acid	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to fatty acid is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071456 cellular response to hypoxia	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to hypoxia is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071466 cellular response to xenobiotic stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to xenobiotic stimulus is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071548 response to dexamethasone	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to dexamethasone is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071559 response to transforming growth factor beta	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to transforming growth factor beta is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0071560 cellular response to transforming growth factor beta stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to transforming growth factor beta stimulus is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0086100 endothelin receptor signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: endothelin receptor signaling pathway is biologically consistent with the curated synthesis for Edn1 and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes the canonical endothelin receptor pathway: ET-1 activates ETA/ETB GPCRs with Gq/11-PLC-calcium/PKC and other downstream signaling.
GO:0090023 positive regulation of neutrophil chemotaxis	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of neutrophil chemotaxis is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0097237 cellular response to toxic substance	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to toxic substance is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0141156 cAMP/PKA signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cAMP/PKA signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0160195 negative regulation of phospholipase C/protein kinase C signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: negative regulation of phospholipase C/protein kinase C signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of non-canonical NF-kappaB signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:1902074 response to salt	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to salt is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of vascular associated smooth muscle cell proliferation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0000122 negative regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of transcription by RNA polymerase II is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0003100 regulation of systemic arterial blood pressure by endothelin	ISO GO_REF:0000119	ACCEPT	Summary: regulation of systemic arterial blood pressure by endothelin is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes ET-1 as a central regulator of vascular tone and blood pressure through receptor-specific endothelin signaling.
GO:0005125 cytokine activity	ISO GO_REF:0000119	MODIFY	Summary: cytokine activity captures the right general biology for Edn1, but a more specific GO term is available. Reason: The current term is too broad or less precise than receptor ligand activity for this gene. Replace with receptor ligand activity to align the annotation with the reviewed evidence. Proposed replacements: receptor ligand activity Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB.
GO:0005179 hormone activity	ISO GO_REF:0000119	ACCEPT	Summary: hormone activity is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon describes Edn1 as encoding a secreted peptide hormone precursor that yields mature endothelin-1, supporting hormone/receptor ligand activity.
GO:0005615 extracellular space	ISO GO_REF:0000119	ACCEPT	Summary: extracellular space is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon states that ET-1 functions as an extracellular ligand produced by endothelial and epithelial cells.
GO:0005737 cytoplasm	ISO GO_REF:0000119	REMOVE	Summary: cytoplasm is not supported as an appropriate annotation for Edn1 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 Edn1 biology. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0007166 cell surface receptor signaling pathway	ISO GO_REF:0000119	MODIFY	Summary: cell surface receptor signaling pathway captures the right general biology for Edn1, 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/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0007186 G protein-coupled receptor signaling pathway	ISO GO_REF:0000119	MODIFY	Summary: G protein-coupled receptor signaling pathway captures the right general biology for Edn1, 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/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0007267 cell-cell signaling	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: cell-cell signaling is biologically consistent with secreted paracrine Edn1 ligand activity but is less specific than endothelin receptor signaling. Reason: Edn1 is a secreted peptide ligand that mediates receptor-dependent communication between cells; retain the broad signaling term as non-core while preferring endothelin receptor signaling and receptor ligand terms. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB.
GO:0008284 positive regulation of cell population proliferation	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of cell population proliferation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0010460 positive regulation of heart rate	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of heart rate is related to reported Edn1 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: PMID:23933587 controlling the fate of neural crest cells through a Dlx5/Dlx6-independent mechanism
GO:0010613 positive regulation of cardiac muscle hypertrophy	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of cardiac muscle hypertrophy is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0010629 negative regulation of gene expression	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of gene expression is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0014824 artery smooth muscle contraction	ISO GO_REF:0000119	ACCEPT	Summary: artery smooth muscle contraction is a direct vascular output of endothelin-1 receptor signaling. Reason: ET-1 is a vasoactive peptide ligand whose ETA/EDNRA signaling in vascular smooth muscle drives vasoconstriction through PLC/calcium signaling, making this term consistent with the curated vascular contraction function. Supporting Evidence: file:mouse/Edn1/Edn1-deep-research-falcon.md ETA (EDNRA/ETAR): classically enriched on vascular smooth muscle cells (VSMCs) and mediates potent, sustained vasoconstriction and growth/remodeling programs.
GO:0014826 vein smooth muscle contraction	ISO GO_REF:0000119	ACCEPT	Summary: vein smooth muscle contraction is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0019722 calcium-mediated signaling	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: calcium-mediated signaling is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0023019 signal transduction involved in regulation of gene expression	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: signal transduction involved in regulation of gene expression is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0030072 peptide hormone secretion	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: peptide hormone secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0030185 nitric oxide transport	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: nitric oxide transport is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0030335 positive regulation of cell migration	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of cell migration is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0031394 positive regulation of prostaglandin biosynthetic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of prostaglandin biosynthetic process is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0031707 endothelin A receptor binding	ISO GO_REF:0000119	ACCEPT	Summary: endothelin A receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETA/EDNRA receptors, supporting endothelin A receptor binding.
GO:0031708 endothelin B receptor binding	ISO GO_REF:0000119	ACCEPT	Summary: endothelin B receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETB/EDNRB receptors, supporting endothelin B receptor binding.
GO:0042310 vasoconstriction	ISO GO_REF:0000119	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0043410 positive regulation of MAPK cascade	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of MAPK cascade is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: phosphatidylinositol 3-kinase/protein kinase B signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045793 positive regulation of cell size	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of cell size is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045840 positive regulation of mitotic nuclear division	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of mitotic nuclear division is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of transcription by RNA polymerase II is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0046330 positive regulation of JNK cascade	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of JNK cascade is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0046887 positive regulation of hormone secretion	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of hormone secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0048661 positive regulation of smooth muscle cell proliferation	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of smooth muscle cell proliferation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0050850 positive regulation of calcium-mediated signaling	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of calcium-mediated signaling is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0051248 negative regulation of protein metabolic process	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of protein metabolic process is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0060298 positive regulation of sarcomere organization	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of sarcomere organization is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0061051 positive regulation of cell growth involved in cardiac muscle cell development	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of cell growth involved in cardiac muscle cell development is related to reported Edn1 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: PMID:15110048 ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the branchial arch system
GO:0070101 positive regulation of chemokine-mediated signaling pathway	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of chemokine-mediated signaling pathway is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0086100 endothelin receptor signaling pathway	ISO GO_REF:0000119	ACCEPT	Summary: endothelin receptor signaling pathway is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes the canonical endothelin receptor pathway: ET-1 activates ETA/ETB GPCRs with Gq/11-PLC-calcium/PKC and other downstream signaling.
GO:0160195 negative regulation of phospholipase C/protein kinase C signal transduction	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: negative regulation of phospholipase C/protein kinase C signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0001821 histamine secretion	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: histamine secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0005615 extracellular space	ISO GO_REF:0000096	ACCEPT	Summary: extracellular space is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon states that ET-1 functions as an extracellular ligand produced by endothelial and epithelial cells.
GO:0007204 positive regulation of cytosolic calcium ion concentration	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of cytosolic calcium ion concentration is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0008217 regulation of blood pressure	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
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 Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0010629 negative regulation of gene expression	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: negative regulation of gene expression is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0014824 artery smooth muscle contraction	ISO GO_REF:0000096	ACCEPT	Summary: artery smooth muscle contraction is a direct vascular output of endothelin-1 receptor signaling. Reason: ET-1 is a vasoactive peptide ligand whose ETA/EDNRA signaling in vascular smooth muscle drives vasoconstriction through PLC/calcium signaling, making this term consistent with the curated vascular contraction function. Supporting Evidence: file:mouse/Edn1/Edn1-deep-research-falcon.md ETA (EDNRA/ETAR): classically enriched on vascular smooth muscle cells (VSMCs) and mediates potent, sustained vasoconstriction and growth/remodeling programs.
GO:0031707 endothelin A receptor binding	ISO GO_REF:0000096	ACCEPT	Summary: endothelin A receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETA/EDNRA receptors, supporting endothelin A receptor binding.
GO:0031708 endothelin B receptor binding	ISO GO_REF:0000096	ACCEPT	Summary: endothelin B receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETB/EDNRB receptors, supporting endothelin B receptor binding.
GO:0032308 positive regulation of prostaglandin secretion	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of prostaglandin secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0033093 Weibel-Palade body	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Weibel-Palade body localization reflects endothelial regulated storage/secretion of ET-1 precursor-processing components. Reason: This supports regulated endothelial storage and secretion of ET-1, but remains a localization/trafficking context rather than the core ligand signaling role. Supporting Evidence: file:mouse/Edn1/Edn1-deep-research-falcon.md ET-1 precursors and processing components can be stored in endothelial secretory vesicles, particularly Weibel-Palade bodies, with reported co-localization of pro-ET-1 and ECE-1.
GO:0034392 negative regulation of smooth muscle cell apoptotic process	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: negative regulation of smooth muscle cell apoptotic process is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0035556 intracellular signal transduction	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: intracellular signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0042045 epithelial fluid transport	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: epithelial fluid transport is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0042310 vasoconstriction	ISO GO_REF:0000096	ACCEPT	Summary: vasoconstriction is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0042482 positive regulation of odontogenesis	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of odontogenesis is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0042554 superoxide anion generation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: superoxide anion generation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045178 basal part of cell	ISO GO_REF:0000096	UNDECIDED	Summary: The local evidence supports Edn1 as a secreted ligand but does not verify this specific basal-cell localization. Reason: The generic secreted-ligand evidence and Weibel-Palade storage model do not establish a basal part of cell annotation for Edn1.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of transcription by RNA polymerase II is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0045987 positive regulation of smooth muscle contraction	ISO GO_REF:0000096	ACCEPT	Summary: positive regulation of smooth muscle contraction is biologically consistent with the curated synthesis for Edn1 and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon identifies ET-1 as a potent vasoconstrictor whose ETA signaling in vascular smooth muscle promotes sustained contraction.
GO:0046888 negative regulation of hormone secretion	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: negative regulation of hormone secretion is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0048237 rough endoplasmic reticulum lumen	ISO GO_REF:0000096	UNDECIDED	Summary: The local evidence supports Edn1 as a secreted peptide precursor, but does not verify a rough endoplasmic reticulum lumen localization. Reason: Secretory-protein biology alone is not enough to retain this specific automated cellular-component annotation without direct localization evidence.
GO:0051899 membrane depolarization	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: membrane depolarization is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
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 Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of non-canonical NF-kappaB signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of vascular associated smooth muscle cell proliferation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:1900182 positive regulation of protein localization to nucleus	IMP PMID:21525433 Endothelin-1 contributes to increased NFATc3 activation by c...	MARK AS OVER ANNOTATED	Summary: positive regulation of protein localization to nucleus is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:1905653 positive regulation of artery morphogenesis	IMP PMID:20495147 NFATc3 contributes to intermittent hypoxia-induced arterial ...	KEEP AS NON CORE	Summary: positive regulation of artery morphogenesis is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:9671575 dHAND and the related gene, eHAND, are downregulated in the branchial and aortic arches of Edn1-null embryos.
GO:0005615 extracellular space	IDA PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	ACCEPT	Summary: extracellular space is biologically consistent with the curated synthesis for Edn1 and is supported by IDA evidence (PMID:24722437). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon states that ET-1 functions as an extracellular ligand produced by endothelial and epithelial cells.
GO:0048018 receptor ligand activity	IDA PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	ACCEPT	Summary: receptor ligand activity is biologically consistent with the curated synthesis for Edn1 and is supported by IDA evidence (PMID:24722437). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB.
GO:0086100 endothelin receptor signaling pathway	IDA 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 Edn1 and is supported by IDA evidence (PMID:24722437). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes the canonical endothelin receptor pathway: ET-1 activates ETA/ETB GPCRs with Gq/11-PLC-calcium/PKC and other downstream 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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:8152482 have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:23933587 Edn1 and Ednra knock-out mice demonstrate abnormalities in pharyngeal arch artery patterning
GO:0007411 axon guidance	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: axon guidance is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Sympathetic axon guidance: Venous endothelin-1 is a direct guidance cue; Manousiouthakis et al. report that "vascular-derived endothelin controls growth and guidance of the STG axons to the heart."
GO:0008217 regulation of blood pressure	IMP PMID:16868309 Collecting duct-specific knockout of the endothelin B recept...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0048675 axon extension	IDA PMID:18401410 Endothelins are vascular-derived axonal guidance cues for de...	KEEP AS NON CORE	Summary: axon extension is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Sympathetic axon guidance: Venous endothelin-1 is a direct guidance cue; Manousiouthakis et al. report that "vascular-derived endothelin controls growth and guidance of the STG axons to the heart."
GO:0000165 MAPK cascade	IDA PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	MARK AS OVER ANNOTATED	Summary: MAPK cascade is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0000165 MAPK cascade	IMP PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	MARK AS OVER ANNOTATED	Summary: MAPK cascade is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:19111534 The stimulatory effect of hCG on GVBD was partially blocked by the same antagonist.
GO:0071372 cellular response to follicle-stimulating hormone stimulus	IDA PMID:19111534 Paracrine regulation of the resumption of oocyte meiosis by ...	UNDECIDED	Summary: The cited oocyte paper supports LH/hCG-responsive Edn1 signaling, but does not directly establish a follicle-stimulating hormone response. Reason: Retaining this FSH-specific annotation requires evidence beyond the LH/hCG and ET-1/EDNRA oocyte-maturation results in the available citation.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:19111534 in response to the preovulatory luteinizing hormone (LH)/human chorionic gonadotropin (hCG) stimulation.
GO:1903537 meiotic cell cycle process involved in oocyte maturation	IDA 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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:19111534 treatment with endothelin-1 promoted oocyte GVBD.
GO:0010467 gene expression	IDA PMID:20929948 Endothelin receptor type A expression defines a distinct car...	KEEP AS NON CORE	Summary: gene expression is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0070371 ERK1 and ERK2 cascade	IDA PMID:20929948 Endothelin receptor type A expression defines a distinct car...	KEEP AS NON CORE	Summary: ERK1 and ERK2 cascade is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0008217 regulation of blood pressure	IMP PMID:20516397 Low blood pressure in endothelial cell-specific endothelin 1...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0010467 gene expression	IMP PMID:20516397 Low blood pressure in endothelial cell-specific endothelin 1...	KEEP AS NON CORE	Summary: gene expression is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:23933587 Edn1/Ednra signaling is involved in pharyngeal artery development by controlling the fate of neural crest cells
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:23933587 controlling the fate of neural crest cells through a Dlx5/Dlx6-independent mechanism
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:23933587 Edn1 and Ednra knock-out mice demonstrate abnormalities in pharyngeal arch artery patterning
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:23933587 Edn1 and Ednra knock-out mice demonstrate abnormalities in pharyngeal arch artery patterning
GO:0070294 renal sodium ion absorption	IDA 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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
GO:0007005 mitochondrion organization	IDA PMID:27899487 Glomerular Endothelial Mitochondrial Dysfunction Is Essentia...	KEEP AS NON CORE	Summary: mitochondrion organization is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:15110048 ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the branchial arch system
GO:0001975 response to amphetamine	IMP PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	MARK AS OVER ANNOTATED	Summary: response to amphetamine is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0003253 cardiac neural crest cell migration involved in outflow tract morphogenesis	IDA 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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:31219639 Cdc42 is part of the signaling pathway activated by endothelin specifically in OFT CNCC to control their migration.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Sympathetic axon guidance: Venous endothelin-1 is a direct guidance cue; Manousiouthakis et al. report that "vascular-derived endothelin controls growth and guidance of the STG axons to the heart."
GO:0006468 protein phosphorylation	IDA PMID:31219639 Cdc42 activation by endothelin regulates neural crest cell m...	MODIFY	Summary: protein phosphorylation captures the right general biology for Edn1, 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/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
GO:0010467 gene expression	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: gene expression is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0031175 neuron projection development	IDA PMID:24875861 Venous endothelin guides sympathetic innervation of the deve...	KEEP AS NON CORE	Summary: neuron projection development is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Sympathetic axon guidance: Venous endothelin-1 is a direct guidance cue; Manousiouthakis et al. report that "vascular-derived endothelin controls growth and guidance of the STG axons to the heart."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Sympathetic axon guidance: Venous endothelin-1 is a direct guidance cue; Manousiouthakis et al. report that "vascular-derived endothelin controls growth and guidance of the STG axons to the heart."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Sympathetic axon guidance: Venous endothelin-1 is a direct guidance cue; Manousiouthakis et al. report that "vascular-derived endothelin controls growth and guidance of the STG axons to the heart."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0086100 endothelin receptor signaling pathway	IDA 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 Edn1 and is supported by IDA evidence (PMID:31219639). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes the canonical endothelin receptor pathway: ET-1 activates ETA/ETB GPCRs with Gq/11-PLC-calcium/PKC and other downstream signaling.
GO:0097492 sympathetic neuron axon guidance	IMP PMID:30735130 Venous endothelin modulates responsiveness of cardiac sympat...	KEEP AS NON CORE	Summary: sympathetic neuron axon guidance is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Sympathetic axon guidance: Venous endothelin-1 is a direct guidance cue; Manousiouthakis et al. report that "vascular-derived endothelin controls growth and guidance of the STG axons to the heart."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
GO:0006366 transcription by RNA polymerase II	IDA PMID:27026367 Endothelin-1 Induces Proteinuria by Heparanase-Mediated Disr...	MARK AS OVER ANNOTATED	Summary: transcription by RNA polymerase II is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0006874 intracellular calcium ion homeostasis	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	KEEP AS NON CORE	Summary: intracellular calcium ion homeostasis is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
GO:0006874 intracellular calcium ion homeostasis	IDA PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	KEEP AS NON CORE	Summary: intracellular calcium ion homeostasis is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
GO:0010467 gene expression	IDA PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	KEEP AS NON CORE	Summary: gene expression is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0060070 canonical Wnt signaling pathway	IDA PMID:24722437 Direct action of endothelin-1 on podocytes promotes diabetic...	KEEP AS NON CORE	Summary: canonical Wnt signaling pathway is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0070301 cellular response to hydrogen peroxide	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: cellular response to hydrogen peroxide is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Kidney and podocyte disease evidence: Endothelin-1 stimulation of primary mouse podocytes "elicited rapid calcium transients mediated by endothelin type A receptors (ETARs) and endothelin type B receptors (ETBRs)" and Ednra-mediated glomerular crosstalk is reported in diabetic kidney models.
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 Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
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 Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
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 Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0141156 cAMP/PKA signal transduction	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: cAMP/PKA signal transduction is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:2001259 positive regulation of cation channel activity	ISO PMID:30990108 ET(A)R and protein kinase A pathway mediate ET-1 sensitizati...	MARK AS OVER ANNOTATED	Summary: positive regulation of cation channel activity is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0031583 phospholipase D-activating G protein-coupled receptor signaling pathway	IDA PMID:8978712 Endothelin stimulates phospholipase D in striatal astrocytes...	KEEP AS NON CORE	Summary: phospholipase D-activating G protein-coupled receptor signaling pathway is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol."
GO:0009953 dorsal/ventral pattern formation	IMP PMID:15110048 Endothelin-1 regulates the dorsoventral branchial arch patte...	KEEP AS NON CORE	Summary: dorsal/ventral pattern formation is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:15110048 ET-1/EdnrA signaling may contribute to the dorsoventral axis patterning of the branchial arch system
GO:0086100 endothelin receptor signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: endothelin receptor signaling pathway is biologically consistent with the curated synthesis for Edn1 and is supported by ISS evidence (GO_REF:0000024). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon summarizes the canonical endothelin receptor pathway: ET-1 activates ETA/ETB GPCRs with Gq/11-PLC-calcium/PKC and other downstream signaling.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IGI PMID:15632412 Collecting duct-specific knockout of endothelin-1 alters vas...	KEEP AS NON CORE	Summary: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol."
GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IDA PMID:2542249 A novel vasoactive peptide endothelin stimulates mitogenesis...	KEEP AS NON CORE	Summary: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol."
GO:0035810 positive regulation of urine volume	IMP PMID:15632412 Collecting duct-specific knockout of endothelin-1 alters vas...	KEEP AS NON CORE	Summary: positive regulation of urine volume is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0035810 positive regulation of urine volume	IGI PMID:15632412 Collecting duct-specific knockout of endothelin-1 alters vas...	KEEP AS NON CORE	Summary: positive regulation of urine volume is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0035815 positive regulation of renal sodium excretion	IMP PMID:15314687 Collecting duct-specific knockout of endothelin-1 causes hyp...	KEEP AS NON CORE	Summary: positive regulation of renal sodium excretion is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0006885 regulation of pH	IDA PMID:11413164 Endothelin-1/endothelin-B receptor-mediated increases in NHE...	KEEP AS NON CORE	Summary: regulation of pH is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0001501 skeletal system development	IMP PMID:8152482 Elevated blood pressure and craniofacial abnormalities in mi...	KEEP AS NON CORE	Summary: skeletal system development is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
GO:0001569 branching involved in blood vessel morphogenesis	IMP PMID:7615798 Aortic arch malformations and ventricular septal defect in m...	KEEP AS NON CORE	Summary: branching involved in blood vessel morphogenesis is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
GO:0001666 response to hypoxia	IMP PMID:8764295 Impaired ventilatory responses to hypoxia and hypercapnia in...	KEEP AS NON CORE	Summary: response to hypoxia is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0005102 signaling receptor binding	IDA PMID:2542249 A novel vasoactive peptide endothelin stimulates mitogenesis...	MODIFY	Summary: signaling receptor binding captures the right general biology for Edn1, but a more specific GO term is available. Reason: The current term is too broad or less precise than receptor ligand activity for this gene. Replace with receptor ligand activity to align the annotation with the reviewed evidence. Proposed replacements: receptor ligand activity Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB.
GO:0005102 signaling receptor binding	IDA PMID:8680799 Developmental changes in cerebellar endothelin-1 receptors i...	MODIFY	Summary: signaling receptor binding captures the right general biology for Edn1, but a more specific GO term is available. Reason: The current term is too broad or less precise than receptor ligand activity for this gene. Replace with receptor ligand activity to align the annotation with the reviewed evidence. Proposed replacements: receptor ligand activity Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB.
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway	IDA PMID:2542249 A novel vasoactive peptide endothelin stimulates mitogenesis...	MODIFY	Summary: phospholipase C-activating G protein-coupled receptor signaling pathway captures the right general biology for Edn1, 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/Edn1/Edn1-notes.md Core receptor binding and signaling: Endothelin stimulates high-affinity receptor binding and phospholipase C signaling in fibroblasts; the abstract reports that endothelin "specifically binds to a single class of high affinity receptors" and "stimulates phospholipase C with the production of second messengers inositol trisphosphate and 1,2-diacylglycerol."
GO:0007507 heart development	IMP PMID:7615798 Aortic arch malformations and ventricular septal defect in m...	KEEP AS NON CORE	Summary: heart development is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
GO:0008217 regulation of blood pressure	IMP PMID:8152482 Elevated blood pressure and craniofacial abnormalities in mi...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0008284 positive regulation of cell population proliferation	IDA PMID:2542249 A novel vasoactive peptide endothelin stimulates mitogenesis...	MARK AS OVER ANNOTATED	Summary: positive regulation of cell population proliferation is related to reported Edn1 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/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
GO:0014032 neural crest cell development	IMP PMID:9671575 A signaling cascade involving endothelin-1, dHAND and msx1 r...	KEEP AS NON CORE	Summary: neural crest cell development is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:9671575 A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme.
GO:0042474 middle ear morphogenesis	IMP PMID:8152482 Elevated blood pressure and craniofacial abnormalities in mi...	UNDECIDED	Summary: The available local evidence supports pharyngeal-arch-derived craniofacial abnormalities but does not directly verify middle ear morphogenesis. Reason: Retaining this specific developmental annotation requires direct middle-ear evidence rather than generic pharyngeal arch or cardiovascular phenotype support.
GO:0043179 rhythmic excitation	IMP PMID:8764295 Impaired ventilatory responses to hypoxia and hypercapnia in...	KEEP AS NON CORE	Summary: rhythmic excitation is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0045987 positive regulation of smooth muscle contraction	IDA PMID:8010105 Effects of endothelin-1 on isolated uterine horns in estroge...	ACCEPT	Summary: positive regulation of smooth muscle contraction is biologically consistent with the curated synthesis for Edn1 and is supported by IDA evidence (PMID:8010105). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure." file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon identifies ET-1 as a potent vasoconstrictor whose ETA signaling in vascular smooth muscle promotes sustained contraction.
GO:0048514 blood vessel morphogenesis	IMP PMID:7615798 Aortic arch malformations and ventricular septal defect in m...	KEEP AS NON CORE	Summary: blood vessel morphogenesis is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
GO:0051216 cartilage development	IMP PMID:8152482 Elevated blood pressure and craniofacial abnormalities in mi...	KEEP AS NON CORE	Summary: cartilage development is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
GO:0005615 extracellular space	IDA PMID:15314687 Collecting duct-specific knockout of endothelin-1 causes hyp...	ACCEPT	Summary: extracellular space is biologically consistent with the curated synthesis for Edn1 and is supported by IDA evidence (PMID:15314687). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon states that ET-1 functions as an extracellular ligand produced by endothelial and epithelial cells.
GO:0007589 body fluid secretion	IMP PMID:15314687 Collecting duct-specific knockout of endothelin-1 causes hyp...	KEEP AS NON CORE	Summary: body fluid secretion is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0008217 regulation of blood pressure	IMP PMID:15314687 Collecting duct-specific knockout of endothelin-1 causes hyp...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Cardiovascular development: Edn1-/- mice have "cardiovascular malformations including interrupted aortic arch ... and ventricular septal defect with abnormalities of the outflow tract."
GO:0031707 endothelin A receptor binding	IPI PMID:9449664 Cranial and cardiac neural crest defects in endothelin-A rec...	ACCEPT	Summary: endothelin A receptor binding is biologically consistent with the curated synthesis for Edn1 and is supported by IPI evidence (PMID:9449664). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Edn1; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Core ligand identity: Edn1 encodes preproendothelin-1, processed to endothelin-1, a secreted vasoactive peptide ligand for endothelin receptors EDNRA and EDNRB. file:mouse/Edn1/Edn1-deep-research-falcon.md Falcon reports that mature ET-1 signals through ETA/EDNRA receptors, supporting endothelin A receptor binding.
GO:0005515 protein binding	IPI PMID:12441350 The first inner loop of endothelin receptor type B is necess...	REMOVE	Summary: protein binding is not supported as an appropriate annotation for Edn1 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 Edn1 biology. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Curation judgment: broad signaling outputs such as MAPK, ERK, JNK, PKA, calcium homeostasis, transcription, proliferation, toxic-substance response, hypoxia response, and many hormone-response terms are downstream or context-specific readouts of endothelin receptor activation.
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 Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
GO:0008217 regulation of blood pressure	IMP PMID:10626068 Endothelin in the central control of cardiovascular and resp...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Edn1 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 Edn1 activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."
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 Edn1, 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/Edn1/Edn1-notes.md Vascular and blood-pressure physiology: Edn1-null mice "die of respiratory failure at birth and have morphological abnormalities of the pharyngeal-arch-derived craniofacial tissues and organs"; heterozygotes "develop elevated blood pressure."

Gene Description

Existing Annotations Review

Core Functions

Mature endothelin-1 is a secreted peptide receptor ligand that binds endothelin A and B receptors to activate endothelin receptor signaling and regulate vascular tone, smooth muscle contraction, and blood-pressure physiology.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

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