Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0001822 kidney development	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: kidney development is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.
GO:0008217 regulation of blood pressure	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0038166 angiotensin-activated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations." file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0007204 positive regulation of cytosolic calcium ion concentration	IBA GO_REF:0000033	ACCEPT	Summary: positive regulation of cytosolic calcium ion concentration is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations." file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0001596 angiotensin type I receptor activity	IBA GO_REF:0000033	ACCEPT	Summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity. file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0006954 inflammatory response	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: inflammatory response is a broad downstream phenotype and is not directly established as an Agtr1a-specific annotation by the reviewed evidence. Reason: The curated model is better captured by AT1A receptor activity, angiotensin-activated PLC/calcium signaling, and renal/vascular blood-pressure terms rather than a generic inflammatory-response transfer. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0003081 regulation of systemic arterial blood pressure by renin-angiotensin	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: regulation of systemic arterial blood pressure by renin-angiotensin is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0004930 G protein-coupled receptor activity	IEA GO_REF:0000120	MODIFY	Summary: G protein-coupled receptor activity captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin type I receptor activity for this gene. Replace with angiotensin type I receptor activity to align the annotation with the reviewed evidence. Proposed replacements: angiotensin type I receptor activity Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0004945 angiotensin type II receptor activity	IEA GO_REF:0000002	MODIFY	Summary: angiotensin type II receptor activity captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin type I receptor activity for this gene. Replace with angiotensin type I receptor activity to align the annotation with the reviewed evidence. Proposed replacements: angiotensin type I receptor activity Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IEA evidence (GO_REF:0000120). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0007165 signal transduction	IEA GO_REF:0000043	MODIFY	Summary: signal transduction captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000120	MODIFY	Summary: G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0016020 membrane	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: membrane is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0019229 regulation of vasoconstriction	IEA GO_REF:0000002	MODIFY	Summary: regulation of vasoconstriction captures the right general biology for Agtr1a, 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/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0005515 protein binding	IPI PMID:10358057 Cloning and characterization of ATRAP, a novel protein that ...	MARK AS OVER ANNOTATED	Summary: protein binding is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0005515 protein binding	IPI PMID:15757644 The novel angiotensin II type 1 receptor (AT1R)-associated p...	MARK AS OVER ANNOTATED	Summary: protein binding is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0001596 angiotensin type I receptor activity	IEA GO_REF:0000107	ACCEPT	Summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity. file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0001921 positive regulation of receptor recycling	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of receptor recycling is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0002018 renin-angiotensin regulation of aldosterone production	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: renin-angiotensin regulation of aldosterone production is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0005794 Golgi apparatus	IEA GO_REF:0000107	UNDECIDED	Summary: The local evidence supports Agtr1a as a plasma-membrane GPCR but does not verify Golgi localization. Reason: The previous support text described renal blood-pressure physiology and did not justify this specific cellular-component annotation.
GO:0006885 regulation of pH	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: regulation of pH is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway	IEA GO_REF:0000107	MODIFY	Summary: phospholipase C-activating G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than phospholipase C-activating angiotensin-activated signaling pathway for this gene. Replace with phospholipase C-activating angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: phospholipase C-activating angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of cell population proliferation is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0009651 response to salt stress	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to salt stress is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0014823 response to activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to activity is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0016323 basolateral plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: basolateral plasma membrane is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0019901 protein kinase binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: protein kinase binding is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0030425 dendrite	IEA GO_REF:0000107	UNDECIDED	Summary: The local evidence supports brain/CNS roles for Agtr1a but does not verify dendrite localization. Reason: Retaining this cellular-component annotation requires direct localization evidence rather than renal or blood-pressure physiology.
GO:0031410 cytoplasmic vesicle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: cytoplasmic vesicle is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0031748 D1 dopamine receptor binding	IEA GO_REF:0000107	REMOVE	Summary: D1 dopamine receptor binding is not supported as an Agtr1a annotation by the reviewed mouse evidence. Reason: The available evidence supports AT1A angiotensin receptor activity; dopamine receptor papers do not establish direct Agtr1a-D1 receptor binding.
GO:0031968 organelle outer membrane	IEA GO_REF:0000107	REMOVE	Summary: organelle outer membrane is not supported as an appropriate annotation for Agtr1a 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 Agtr1a biology. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0032930 positive regulation of superoxide anion generation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of superoxide anion generation is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0038166 angiotensin-activated signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by IEA evidence (GO_REF:0000107). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations." file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0042310 vasoconstriction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: vasoconstriction is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0042416 dopamine biosynthetic process	IEA GO_REF:0000107	REMOVE	Summary: dopamine biosynthetic process is not supported as an appropriate annotation for Agtr1a 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 Agtr1a biology. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0042756 drinking behavior	IEA GO_REF:0000120	REMOVE	Summary: Drinking behavior is not supported as an Agtr1a-specific annotation by the reviewed mouse evidence. Reason: Direct central angiotensin II experiments separate AT1A-dependent blood-pressure responses from drinking behavior, which requires AT1B. Supporting Evidence: PMID:10880053 the drinking response requires the presence of AT(1B) receptors.
GO:0043627 response to estrogen	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to estrogen is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0045766 positive regulation of angiogenesis	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: positive regulation of angiogenesis is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0045777 positive regulation of blood pressure	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of blood pressure is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0051412 response to corticosterone	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: response to corticosterone is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0055037 recycling endosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: recycling endosome is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0071549 cellular response to dexamethasone stimulus	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: cellular response to dexamethasone stimulus is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of branching involved in ureteric bud morphogenesis is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.
GO:1905665 positive regulation of calcium ion import across plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: positive regulation of calcium ion import across plasma membrane is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:1990776 response to angiotensin	IEA GO_REF:0000107	MODIFY	Summary: response to angiotensin captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0042976 activation of Janus kinase activity	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: activation of Janus kinase activity is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0001596 angiotensin type I receptor activity	ISO GO_REF:0000096	ACCEPT	Summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity. file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0001596 angiotensin type I receptor activity	ISO GO_REF:0000119	ACCEPT	Summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity. file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0001822 kidney development	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: kidney development is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.
GO:0001921 positive regulation of receptor recycling	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of receptor recycling is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0002018 renin-angiotensin regulation of aldosterone production	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: renin-angiotensin regulation of aldosterone production is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0002034 maintenance of blood vessel diameter homeostasis by renin-angiotensin	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: maintenance of blood vessel diameter homeostasis by renin-angiotensin is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0004945 angiotensin type II receptor activity	ISO GO_REF:0000119	MODIFY	Summary: angiotensin type II receptor activity captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin type I receptor activity for this gene. Replace with angiotensin type I receptor activity to align the annotation with the reviewed evidence. Proposed replacements: angiotensin type I receptor activity Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0005794 Golgi apparatus	ISO GO_REF:0000096	UNDECIDED	Summary: The local evidence supports Agtr1a as a plasma-membrane GPCR but does not verify Golgi localization. Reason: The previous support text described renal blood-pressure physiology and did not justify this specific cellular-component annotation.
GO:0005886 plasma membrane	ISO GO_REF:0000096	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0005886 plasma membrane	ISO GO_REF:0000119	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0006885 regulation of pH	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: regulation of pH is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0007186 G protein-coupled receptor signaling pathway	ISO GO_REF:0000096	MODIFY	Summary: G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
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 Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway	ISO GO_REF:0000096	MODIFY	Summary: phospholipase C-activating G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than phospholipase C-activating angiotensin-activated signaling pathway for this gene. Replace with phospholipase C-activating angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: phospholipase C-activating angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway	ISO GO_REF:0000119	MODIFY	Summary: phospholipase C-activating G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than phospholipase C-activating angiotensin-activated signaling pathway for this gene. Replace with phospholipase C-activating angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: phospholipase C-activating angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0007204 positive regulation of cytosolic calcium ion concentration	ISO GO_REF:0000119	ACCEPT	Summary: positive regulation of cytosolic calcium ion concentration is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations." file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0007266 Rho protein signal transduction	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Rho protein signal transduction is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
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 Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0010744 positive regulation of macrophage derived foam cell differentiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: positive regulation of macrophage derived foam cell differentiation is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0016323 basolateral plasma membrane	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: basolateral plasma membrane is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0019229 regulation of vasoconstriction	ISO GO_REF:0000119	MODIFY	Summary: regulation of vasoconstriction captures the right general biology for Agtr1a, 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/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0019722 calcium-mediated signaling	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: calcium-mediated signaling is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0019901 protein kinase binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: protein kinase binding is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0030425 dendrite	ISO GO_REF:0000096	UNDECIDED	Summary: The local evidence supports brain/CNS roles for Agtr1a but does not verify dendrite localization. Reason: Retaining this cellular-component annotation requires direct localization evidence rather than renal or blood-pressure physiology.
GO:0031410 cytoplasmic vesicle	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: cytoplasmic vesicle is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0031711 bradykinin receptor binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: bradykinin receptor binding is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0031748 D1 dopamine receptor binding	ISO GO_REF:0000096	REMOVE	Summary: D1 dopamine receptor binding is not supported as an Agtr1a annotation by the reviewed mouse evidence. Reason: The available evidence supports AT1A angiotensin receptor activity; dopamine receptor papers do not establish direct Agtr1a-D1 receptor binding.
GO:0031968 organelle outer membrane	ISO GO_REF:0000096	REMOVE	Summary: organelle outer membrane is not supported as an appropriate annotation for Agtr1a 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 Agtr1a biology. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0032930 positive regulation of superoxide anion generation	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of superoxide anion generation is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0038166 angiotensin-activated signaling pathway	ISO GO_REF:0000096	ACCEPT	Summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000096). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations." file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0038166 angiotensin-activated signaling pathway	ISO GO_REF:0000119	ACCEPT	Summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations." file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0042310 vasoconstriction	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: vasoconstriction is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0042416 dopamine biosynthetic process	ISO GO_REF:0000096	REMOVE	Summary: dopamine biosynthetic process is not supported as an appropriate annotation for Agtr1a 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 Agtr1a biology. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0042756 drinking behavior	ISO GO_REF:0000096	REMOVE	Summary: Drinking behavior is not supported as an Agtr1a-specific annotation by the reviewed mouse evidence. Reason: Direct central angiotensin II experiments separate AT1A-dependent blood-pressure responses from drinking behavior, which requires AT1B. Supporting Evidence: PMID:10880053 the drinking response requires the presence of AT(1B) receptors.
GO:0043627 response to estrogen	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: response to estrogen is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0045766 positive regulation of angiogenesis	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: positive regulation of angiogenesis is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0045777 positive regulation of blood pressure	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of blood pressure is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0046718 symbiont entry into host cell	ISO GO_REF:0000119	REMOVE	Summary: symbiont entry into host cell is not supported as an appropriate annotation for Agtr1a 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 Agtr1a biology. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0046982 protein heterodimerization activity	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: protein heterodimerization activity is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0055037 recycling endosome	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: recycling endosome is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0060326 cell chemotaxis	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: cell chemotaxis is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0071549 cellular response to dexamethasone stimulus	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: cellular response to dexamethasone stimulus is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0086097 phospholipase C-activating angiotensin-activated signaling pathway	ISO GO_REF:0000119	ACCEPT	Summary: phospholipase C-activating angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of branching involved in ureteric bud morphogenesis is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.
GO:0090205 positive regulation of cholesterol metabolic process	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of cholesterol metabolic process is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:1903589 positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:1905665 positive regulation of calcium ion import across plasma membrane	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: positive regulation of calcium ion import across plasma membrane is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0010467 gene expression	IMP PMID:24206662 Mineralocorticoid receptor phosphorylation regulates ligand ...	KEEP AS NON CORE	Summary: gene expression is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0002034 maintenance of blood vessel diameter homeostasis by renin-angiotensin	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: maintenance of blood vessel diameter homeostasis by renin-angiotensin is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0008217 regulation of blood pressure	IMP PMID:26531127 Age-dependent blood pressure elevation is due to increased v...	KEEP AS NON CORE	Summary: regulation of blood pressure is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0006954 inflammatory response	IGI PMID:19404405 Angiotensin-(1-7) and the g protein-coupled receptor MAS are...	REMOVE	Summary: This paper supports Mas/Ang-(1-7)-dependent renal inflammation, not an Agtr1a-specific inflammatory response. Reason: The cited study explicitly shows the inflammatory effect is preserved when Ang II receptors are absent, so it should not be retained for Agtr1a. Supporting Evidence: PMID:19404405 showing that this effect is AT1 and AT2 independent
GO:0034391 regulation of smooth muscle cell apoptotic process	IGI PMID:19508861 The heterogenous nuclear riboprotein S1-1 regulates AT1 rece...	KEEP AS NON CORE	Summary: regulation of smooth muscle cell apoptotic process is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0034392 negative regulation of smooth muscle cell apoptotic process	IMP PMID:19508861 The heterogenous nuclear riboprotein S1-1 regulates AT1 rece...	KEEP AS NON CORE	Summary: negative regulation of smooth muscle cell apoptotic process is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0008284 positive regulation of cell population proliferation	IMP PMID:19508861 The heterogenous nuclear riboprotein S1-1 regulates AT1 rece...	MARK AS OVER ANNOTATED	Summary: positive regulation of cell population proliferation is related to reported Agtr1a 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/Agtr1a/Agtr1a-notes.md Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.
GO:0002035 brain renin-angiotensin system	IMP PMID:16585392 Role of p90 ribosomal S6 kinase-mediated prorenin-converting...	KEEP AS NON CORE	Summary: brain renin-angiotensin system is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0007507 heart development	IMP PMID:16585392 Role of p90 ribosomal S6 kinase-mediated prorenin-converting...	KEEP AS NON CORE	Summary: heart development is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0001819 positive regulation of cytokine production	IMP PMID:19023134 Serotonin and angiotensin receptors in cardiac fibroblasts c...	KEEP AS NON CORE	Summary: positive regulation of cytokine production is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0045777 positive regulation of blood pressure	IMP PMID:12486173 Mice lacking D5 dopamine receptors have increased sympatheti...	REMOVE	Summary: This dopamine D5 receptor paper does not establish a direct Agtr1a positive regulation of blood pressure annotation. Reason: Other direct Agtr1a blood-pressure annotations are retained, but this source-specific row is based on a dopamine receptor knockout study rather than Agtr1a function. Supporting Evidence: PMID:12486173 Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive.
GO:0045777 positive regulation of blood pressure	IGI PMID:9691085 Disruption of the dopamine D3 receptor gene produces renin-d...	REMOVE	Summary: This dopamine D3 receptor paper does not establish a direct Agtr1a positive regulation of blood pressure annotation. Reason: Other direct Agtr1a blood-pressure annotations are retained, but this source-specific row is based on a dopamine receptor knockout study rather than Agtr1a function. Supporting Evidence: PMID:9691085 disruption of the D3 receptor, a member of the family of D2-like receptors
GO:0045777 positive regulation of blood pressure	IDA PMID:12486173 Mice lacking D5 dopamine receptors have increased sympatheti...	REMOVE	Summary: This dopamine D5 receptor paper does not establish a direct Agtr1a positive regulation of blood pressure annotation. Reason: Other direct Agtr1a blood-pressure annotations are retained, but this source-specific row is based on a dopamine receptor knockout study rather than Agtr1a function. Supporting Evidence: PMID:12486173 Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive.
GO:0005737 cytoplasm	IDA PMID:15499027 Angiotensin II impairs neurovascular coupling in neocortex t...	UNDECIDED	Summary: The cited cerebral microvessel paper supports AT1 localization in vascular cells but does not verify cytoplasm as the appropriate component. Reason: Agtr1a is retained as a membrane GPCR; a cytoplasm annotation needs term-specific localization evidence rather than vascular physiology.
GO:0005886 plasma membrane	IDA PMID:15499027 Angiotensin II impairs neurovascular coupling in neocortex t...	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IDA evidence (PMID:15499027). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0001568 blood vessel development	IGI PMID:9466969 Murine double nullizygotes of the angiotensin type 1A and 1B...	KEEP AS NON CORE	Summary: blood vessel development is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0001822 kidney development	IMP PMID:12167595 Effects of AT(1A) receptor deletion on blood pressure and so...	KEEP AS NON CORE	Summary: kidney development is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.
GO:0001822 kidney development	IGI PMID:9466969 Murine double nullizygotes of the angiotensin type 1A and 1B...	KEEP AS NON CORE	Summary: kidney development is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.
GO:0001991 regulation of systemic arterial blood pressure by circulatory renin-angiotensin	IGI PMID:9466969 Murine double nullizygotes of the angiotensin type 1A and 1B...	KEEP AS NON CORE	Summary: regulation of systemic arterial blood pressure by circulatory renin-angiotensin is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0002001 renin secretion into blood stream	IMP PMID:12167595 Effects of AT(1A) receptor deletion on blood pressure and so...	KEEP AS NON CORE	Summary: renin secretion into blood stream is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0002018 renin-angiotensin regulation of aldosterone production	IMP PMID:12167595 Effects of AT(1A) receptor deletion on blood pressure and so...	KEEP AS NON CORE	Summary: renin-angiotensin regulation of aldosterone production is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0002019 regulation of renal output by angiotensin	IMP PMID:12167595 Effects of AT(1A) receptor deletion on blood pressure and so...	KEEP AS NON CORE	Summary: regulation of renal output by angiotensin is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.
GO:0042756 drinking behavior	IMP PMID:12167595 Effects of AT(1A) receptor deletion on blood pressure and so...	REMOVE	Summary: This renal sodium-balance paper does not support drinking behavior as an Agtr1a-specific annotation. Reason: The cited study supports renal output and blood-pressure physiology; direct central angiotensin II evidence instead assigns drinking behavior primarily to AT1B rather than AT1A. Supporting Evidence: PMID:12167595 These studies demonstrate that mice lacking the AT(1A) receptor have blood pressures sensitive to changes in dietary sodium
GO:0001596 angiotensin type I receptor activity	IDA PMID:12657564 A role for angiotensin II AT1 receptors in ureteric bud cell...	ACCEPT	Summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by IDA evidence (PMID:12657564). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity. file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
GO:0002035 brain renin-angiotensin system	IMP PMID:10880053 Divergent functions of angiotensin II receptor isoforms in t...	KEEP AS NON CORE	Summary: brain renin-angiotensin system is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: PMID:10880053 AT(1A) expression generally exceeding AT(1B) expression
GO:0042756 drinking behavior	IMP PMID:10880053 Divergent functions of angiotensin II receptor isoforms in t...	REMOVE	Summary: Drinking behavior is not supported as an Agtr1a-specific annotation by this direct central angiotensin II study. Reason: The same citation explicitly separates AT1A-dependent blood-pressure responses from drinking behavior, which requires AT1B. Supporting Evidence: PMID:10880053 the drinking response requires the presence of AT(1B) receptors.
GO:0042756 drinking behavior	IGI PMID:10880053 Divergent functions of angiotensin II receptor isoforms in t...	REMOVE	Summary: Drinking behavior is not supported as an Agtr1a-specific annotation by this direct central angiotensin II study. Reason: The same citation explicitly separates AT1A-dependent blood-pressure responses from drinking behavior, which requires AT1B. Supporting Evidence: PMID:10880053 the drinking response requires the presence of AT(1B) receptors.
GO:0005768 endosome	IDA PMID:14718562 Phospholipase D2 localizes to the plasma membrane and regula...	KEEP AS NON CORE	Summary: endosome is supported for Agtr1a 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 Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.
GO:0005886 plasma membrane	IDA PMID:14718562 Phospholipase D2 localizes to the plasma membrane and regula...	ACCEPT	Summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IDA evidence (PMID:14718562). Reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement. Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
GO:0007186 G protein-coupled receptor signaling pathway	IC PMID:12657564 A role for angiotensin II AT1 receptors in ureteric bud cell...	MODIFY	Summary: G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available. Reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence. Proposed replacements: angiotensin-activated signaling pathway Supporting Evidence: file:mouse/Agtr1a/Agtr1a-notes.md Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."

Core Functions

AGTR1A binds angiotensin II as a type 1 angiotensin receptor at the plasma membrane and activates Gq/phospholipase C/calcium signaling that underlies renin-angiotensin control of vasoconstriction, renal output, aldosterone production, and blood pressure.

Molecular Function:

angiotensin type I receptor activity

Directly Involved In:

angiotensin-activated signaling pathway phospholipase C-activating angiotensin-activated signaling pathway positive regulation of cytosolic calcium ion concentration

Cellular Locations:

plasma membrane

Supporting Evidence:

file:mouse/Agtr1a/Agtr1a-notes.md
Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.
file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:

References

file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md

Falcon deep research report for mouse Agtr1a

file:mouse/Agtr1a/Agtr1a-notes.md

Curator notes for mouse Agtr1a review

file:mouse/Agtr1a/Agtr1a-uniprot.txt

UniProtKB record for mouse Agtr1a

file:mouse/Agtr1a/Agtr1a-goa.tsv

QuickGO export for mouse Agtr1a

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

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

GO_REF:0000096

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

GO_REF:0000107

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

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

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

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10358057

Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor.

PMID:10880053

Divergent functions of angiotensin II receptor isoforms in the brain.

PMID:12167595

Effects of AT(1A) receptor deletion on blood pressure and sodium excretion during altered dietary salt intake.

PMID:12486173

Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive.

PMID:12657564

A role for angiotensin II AT1 receptors in ureteric bud cell branching.

PMID:14718562

Phospholipase D2 localizes to the plasma membrane and regulates angiotensin II receptor endocytosis.

PMID:15499027

Angiotensin II impairs neurovascular coupling in neocortex through NADPH oxidase-derived radicals.

PMID:15757644

The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy.

PMID:16585392

Role of p90 ribosomal S6 kinase-mediated prorenin-converting enzyme in ischemic and diabetic myocardium.

PMID:19023134

Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy.

PMID:19404405

Angiotensin-(1-7) and the g protein-coupled receptor MAS are key players in renal inflammation.

PMID:19508861

The heterogenous nuclear riboprotein S1-1 regulates AT1 receptor gene expression via transcriptional and posttranscriptional mechanisms.

PMID:24206662

Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia.

PMID:26531127

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

PMID:9466969

Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes.

PMID:9691085

Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension.

Suggested Experiments

Experiment: Measure Ang II-induced PLC activation, calcium mobilization, and ERK/Rho pathway activation in Agtr1a-null and rescued mouse cells, including antagonist controls and Agtr1b comparison.

Hypothesis: The clearest direct AGTR1A pathway annotation is Gq/PLC/calcium signaling downstream of angiotensin II.

Type: cell signaling rescue assay

📚 Additional Documentation

Deep Research Falcon

(Agtr1a-deep-research-falcon.md)

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organism: mouse
gene_id: Agtr1a
gene_symbol: Agtr1a
uniprot_accession: P29754
protein_description: 'RecName: Full=Type-1 angiotensin II receptor A {ECO:0000305};
AltName: Full=Angiotensin II type-1 receptor A {ECO:0000303|PubMed:1497638}; Short=AT1
receptor A {ECO:0000303|PubMed:1599461};'
gene_info: Name=Agtr1a; Synonyms=Agtr1;
organism_full: Mus musculus (Mouse).
protein_family: Belongs to the G-protein coupled receptor 1 family.
protein_domains: ATII_AT1_rcpt. (IPR000190); ATII_rcpt. (IPR000248); CCR1-9-like.
(IPR050119); GPCR_Rhodpsn. (IPR000276); GPCR_Rhodpsn_7TM. (IPR017452)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

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

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P29754
Protein Description: RecName: Full=Type-1 angiotensin II receptor A {ECO:0000305}; AltName: Full=Angiotensin II type-1 receptor A {ECO:0000303|PubMed:1497638}; Short=AT1 receptor A {ECO:0000303|PubMed:1599461};
Gene Information: Name=Agtr1a; Synonyms=Agtr1;
Organism (full): Mus musculus (Mouse).
Protein Family: Belongs to the G-protein coupled receptor 1 family.
Key Domains: ATII_AT1_rcpt. (IPR000190); ATII_rcpt. (IPR000248); CCR1-9-like. (IPR050119); GPCR_Rhodpsn. (IPR000276); GPCR_Rhodpsn_7TM. (IPR017452)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Agtr1a" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

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

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Agtr1a' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene Agtr1a (gene ID: Agtr1a, UniProt: P29754) in mouse.

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

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

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

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

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

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

Output

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

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

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

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

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

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P29754
Protein Description: RecName: Full=Type-1 angiotensin II receptor A {ECO:0000305}; AltName: Full=Angiotensin II type-1 receptor A {ECO:0000303|PubMed:1497638}; Short=AT1 receptor A {ECO:0000303|PubMed:1599461};
Gene Information: Name=Agtr1a; Synonyms=Agtr1;
Organism (full): Mus musculus (Mouse).
Protein Family: Belongs to the G-protein coupled receptor 1 family.
Key Domains: ATII_AT1_rcpt. (IPR000190); ATII_rcpt. (IPR000248); CCR1-9-like. (IPR050119); GPCR_Rhodpsn. (IPR000276); GPCR_Rhodpsn_7TM. (IPR017452)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "Agtr1a" matches the protein description above
Verify the organism is correct: Mus musculus (Mouse).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

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

Research Target:

Please provide a comprehensive research report on the gene Agtr1a (gene ID: Agtr1a, UniProt: P29754) in mouse.

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

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

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

Comprehensive Research Report: Mouse Agtr1a (Angiotensin II Type-1 Receptor A; AT1aR) Functional Annotation

0) Target identity verification (critical disambiguation)

The literature reviewed matches the mouse (Mus musculus) Agtr1a gene encoding the angiotensin II type 1a receptor (AT1aR), a 7‑transmembrane class A (rhodopsin-like) GPCR and the dominant murine AT1 receptor isoform in many tissues. (cui2023theroleof pages 7-13, takayama2023angiotensiniitype pages 1-2)

Rodents express two AT1 receptor isoforms (AT1a/Agtr1a and AT1b/Agtr1b), whereas humans have a single AGTR1 gene; Agtr1a is repeatedly described as the main/major murine AT1 isoform and mouse homolog corresponding to human AGTR1. (takayama2023angiotensiniitype pages 1-2, alhajoj2024assessingadenoviraldelivery pages 39-42)

1) Key concepts and definitions (current understanding)

1.1 Receptor/ligand system

Agtr1a/AT1aR is the principal receptor mediating many effects of the renin–angiotensin system (RAS) effector peptide angiotensin II (Ang II). In vascular tissues, Ang II acting at AT1 receptors produces smooth muscle contraction and increases vascular resistance and blood pressure. (nadasy2024directvasculareffects pages 1-2)

1.2 Canonical (G protein) signaling

AT1 receptors (including AT1aR) are commonly characterized as Gq/11‑coupled GPCRs. Upon Ang II binding, canonical signaling proceeds via PLC activation → PIP2 cleavage → IP3 + DAG → intracellular Ca2+ release + PKC activation, with downstream engagement of kinase pathways and oxidative signaling. (singh2024implicationsofβarrestin pages 1-3)

Downstream consequences in vascular pathobiology include activation of signaling modules (e.g., MAPK/ERK pathways) and transcriptional programs associated with inflammation and remodeling. (nadasy2024directvasculareffects pages 1-2)

1.3 Noncanonical signaling: β‑arrestin recruitment, internalization, and “biased agonism”

AT1 receptor C‑terminal phosphorylation by GRKs recruits β‑arrestin‑1/2, which (i) desensitizes G‑protein signaling, (ii) drives clathrin-dependent internalization, and (iii) can scaffold distinct signaling modules (including MAPK and PI3K pathways) from internalized receptor complexes. (mathieu2024insightsintothe pages 3-4)

“Biased agonism” refers to ligands that preferentially activate one signaling arm (e.g., β‑arrestin) over another (e.g., Gq). In the AT1R field, peptides such as TRV027 (TRV120027) and SII‑AngII are used as β‑arrestin‑biased ligands to probe or exploit these pathways. (mathieu2024insightsintothe pages 3-4, singh2024implicationsofβarrestin pages 1-3)

2) Subcellular and tissue/cellular localization relevant to function

2.1 Plasma membrane receptor in vascular smooth muscle: vasoconstriction and mechanosensing

Recent mechanistic work in mouse resistance vessels supports a central role for AT1aR in myogenic vasoconstriction and mechanosensory control of vascular tone. In these preparations, Gq/11-dependent signaling is required for myogenic constriction, while β‑arrestin‑biased ligands did not reproduce the same vasoconstrictor responses. (cui2023theroleof pages 7-13, cui2023theroleof pages 40-41)

2.2 Vascular endothelium in kidney and brain microvessels

In vivo imaging demonstrates that Ang II can act directly on endothelial cells within kidney and brain microvessels to raise endothelial intracellular Ca2+ and stimulate NO production; these responses are sensitive to the AT1R antagonist losartan (and not blocked by AT2R blockade), implicating endothelial AT1R signaling in vivo. (calderon2024angiotensiniidirectly pages 1-2)

2.3 Renal tubule epithelium: proximal tubule and distal nephron

A 2024 kidney-tubule-specific AT1aR deletion model (Pax8-rtTA/tet-on; Agtr1a-floxed) provides direct evidence that renal tubular AT1aR regulates proximal tubule membrane potential and transport protein expression (e.g., NHE3, Kir4.2) and is linked to systemic blood pressure regulation. (duan2024roleofangiotensin pages 1-3)

2.4 CNS circuits (energy balance and sympathetic regulation)

Agtr1a/AT1aR expression in hypothalamic AgRP neurons supports integrative roles in cardiometabolic regulation; notably, obesity can be associated with a G-protein “signal switch” in a subset of AT1aR-expressing neurons (from Gi-like inhibitory responses to Gq-like excitatory responses), linking AT1aR signaling state to resting metabolic rate adaptation. (balapattabi2023angiotensinat1areceptor pages 1-3)

3) Pathways and mechanistic roles (functional annotation)

3.1 Primary molecular function

Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through:
- Gq/11 → PLC → IP3/DAG → Ca2+/PKC (canonical), and
- β‑arrestin recruitment → desensitization/internalization + β‑arrestin–scaffolded signaling (noncanonical). (singh2024implicationsofβarrestin pages 1-3, mathieu2024insightsintothe pages 3-4)

3.2 Vascular function: tone, remodeling, and aneurysm biology

AT1R activation has an acute vasoconstrictor role (via G proteins) and is implicated in chronic vascular inflammation/fibrosis; β‑arrestin signaling can regulate receptor trafficking and longer-term programs in cell growth/survival, motivating pharmacologic strategies that separate these arms. (jara2023distinctmechanismsof pages 1-3)

In an Ang II–driven aneurysm model (ApoE−/− on high-fat diet), Ang II infusion produced aneurysm/dissection outcomes that were preventable by either a standard AT1R blocker or a β‑arrestin‑biased agonist (see statistics below). (jara2023distinctmechanismsof pages 1-3, jara2023distinctmechanismsof pages 14-15)

3.3 Renal tubular function: membrane potential and sodium handling

Kidney-tubule AT1aR deletion reduced expression of NHE3 and Kir4.2 in proximal tubule and altered proximal tubule membrane potential; it also altered distal nephron channel processing (increased cleaved γENaC) and increased amiloride-sensitive Na+ currents in cortical collecting duct, consistent with segment-specific roles of tubular AT1aR in transporter/channel regulation. (duan2024roleofangiotensin pages 1-3)

3.4 Endothelial counter-regulation of vasoconstriction

Direct endothelial AT1R signaling in kidney/brain microvessels evokes Ca2+ and NO responses that may counterbalance vasoconstriction; these responses are attenuated in hypertensive/fibrotic disease models and correlate with microvascular pathology (e.g., endothelial shedding, microthrombi). (calderon2024angiotensiniidirectly pages 1-2)

4) Recent developments and latest research (prioritizing 2023–2024)

4.1 Cell-type–specific genetics as a major methodological advance

A 2024 Hypertension “milestones” review highlights the central role of Agtr1a-floxed mice (developed earlier but now widely deployed) to resolve cell-specific AT1aR functions in proximal tubules versus vascular smooth muscle, including dissociation of blood pressure phenotypes from vascular remodeling outcomes. (Publication date: May 2024; URL: https://doi.org/10.1161/hypertensionaha.123.21365) (eguchi2024milestonepaperson pages 3-4)

4.2 β‑arrestin signaling: from receptor biology to therapeutic stratification

A 2024 Hypertension review synthesizes evidence that AT1R β‑arrestin signaling can be protective or maladaptive depending on context, and discusses the need for patient/model stratification when targeting AT1R signaling bias. (Publication date: Jan 2024; URL: https://doi.org/10.1161/hypertensionaha.123.19419) (mathieu2024insightsintothe pages 6-8)

A 2024 Cellular Signalling review provides a concise mechanistic picture of how biased ligands reshape receptor trafficking and signaling topology (e.g., prolonged endosomal/cytoplasmic ERK signaling), emphasizing implications for cardiovascular drug discovery. (Publication date: Dec 2024; URL: https://doi.org/10.1016/j.cellsig.2024.111410) (singh2024implicationsofβarrestin pages 1-3)

4.3 Direct in vivo endothelial signaling by Ang II

A 2024 JAHA intravital imaging study directly visualized Ang II–evoked endothelial Ca2+ and NO signaling in kidney and brain microvessels, demonstrating that the endothelial response is AT1R-dependent (losartan-sensitive) and becomes blunted in hypertension/fibrosis models. (Publication date: May 2024; URL: https://doi.org/10.1161/jaha.123.033998) (calderon2024angiotensiniidirectly pages 1-2)

5) Current applications and real-world implementations

5.1 Pharmacology: ARBs as standard AT1R/AT1aR pathway inhibitors

Clinically used angiotensin receptor blockers (ARBs) are characterized as neutral/balanced antagonists that block both G‑protein and β‑arrestin components of AT1R signaling. (mathieu2024insightsintothe pages 3-4)

In experimental settings, losartan is commonly used for mechanistic inference; for example, losartan blocked Ang II–evoked endothelial Ca2+ and NO responses in vivo. (calderon2024angiotensiniidirectly pages 1-2)

5.2 Experimental therapeutics: β‑arrestin‑biased ligands (TRV027)

β‑arrestin‑biased ligands are used to attempt to preserve or redirect potentially beneficial AT1R signaling. In cardiovascular translation, TRV027 was evaluated in a Phase IIb BLAST‑AHF trial (reported in review form) with 621 patients randomized to placebo or TRV027 at 1, 5, or 25 mg/hr IV; the drug was well tolerated but did not meet primary endpoints in the overall cohort, with post-hoc signals suggesting benefit in higher systolic BP tertiles. (singh2024implicationsofβarrestin pages 3-5, mathieu2024insightsintothe pages 6-8)

5.3 Genetic models as routine “implementations” for functional annotation

Agtr1a global knockouts, Agtr1a-floxed alleles, and tissue-specific Cre strategies (kidney tubules; vascular smooth muscle; brain regions) now represent standard experimental infrastructure for assigning cell-type contributions to blood pressure control, vascular remodeling, renal transport, and CNS regulation. (eguchi2024milestonepaperson pages 3-4, duan2024roleofangiotensin pages 1-3)

6) Quantitative statistics and data points from recent studies

6.1 Endothelial microvessel signaling (2024)

Acute systemic Ang II increased endothelial intracellular Ca2+ by >4‑fold in kidney and brain microvessels and increased NO reporter signal by >1.5‑fold; both were blocked by losartan. (Calderon et al., May 2024; https://doi.org/10.1161/jaha.123.033998) (calderon2024angiotensiniidirectly pages 1-2)

6.2 Aortic aneurysm/dissection outcomes and pharmacologic prevention (2023)

In Ang II–infused ApoE−/− males on high-fat diet, Ang II produced aneurysm in ≈67% with substantial mortality, and ≈13% mortality occurred from aortic arch dissection without aneurysm; co-infusion with TRV027 or olmesartan prevented Ang II–induced aneurysm-associated mortality (with distinct mechanistic signatures). (Jara et al., Feb 2023; https://doi.org/10.1161/hypertensionaha.122.19232) (jara2023distinctmechanismsof pages 1-3, jara2023distinctmechanismsof pages 14-15)

6.3 Blood pressure phenotype in cell-specific genetic models (2024 review summary)

A Hypertension milestones review reports that a knock-in SM22α VSMC AT1aR deletion reduced baseline blood pressure by 7 mmHg and attenuated Ang II–mediated hypertension, illustrating how cell-targeting strategy can alter inferred contributions of VSMC AT1aR to blood pressure control. (Eguchi et al., May 2024; https://doi.org/10.1161/hypertensionaha.123.21365) (eguchi2024milestonepaperson pages 3-4)

6.4 Kidney-tubule-specific knockout validation and BP phenotype (2024; figure-based evidence)

Duan et al. provide figure-level evidence of reduced Agtr1a mRNA in kidney-tubule-specific knockout animals and a corresponding lower systolic blood pressure phenotype relative to floxed controls, along with baseline phenotype tables. (Duan et al., Jan 2024; https://doi.org/10.1161/hypertensionaha.123.21389) (duan2024roleofangiotensin media 76ecb2b3, duan2024roleofangiotensin media b9bb5956, duan2024roleofangiotensin media baf624f1)

7) Expert opinions and authoritative synthesis (2024)

Recent expert reviews in Hypertension emphasize that AT1R/AT1aR signaling cannot be reduced to a single “good vs bad” axis: β‑arrestin signaling can be protective (e.g., improved hemodynamics/endothelial function in some models) or maladaptive (e.g., contributions to aneurysm-related inflammation and vascular smooth muscle migration), implying that therapeutic targeting may require disease- and patient-specific stratification (e.g., baseline SBP or plasma renin activity). (Mathieu et al., Jan 2024; https://doi.org/10.1161/hypertensionaha.123.19419) (mathieu2024insightsintothe pages 6-8)

A 2024 systematic short review of direct vascular Ang II effects underscores the multiplicity of AT1R signaling pathways (including Gq/11 and arrestin-dependent signaling) and links these to inflammatory and fibrotic vascular remodeling programs, supporting the concept that AT1 receptor biology spans acute tone regulation and chronic transcriptional remodeling. (Nádasy et al., Dec 2024; https://doi.org/10.3390/ijms26010113) (nadasy2024directvasculareffects pages 1-2)

8) Summary functional annotation statement (for databases/curation)

Agtr1a encodes the mouse angiotensin II type 1a receptor (AT1aR), a predominant murine AT1 GPCR that localizes primarily to the plasma membrane and transduces Ang II signals through Gq/PLC/IP3–DAG/Ca2+/PKC and β‑arrestin–dependent receptor trafficking and signaling. In vivo and genetic evidence supports critical roles in vascular tone and mechanosensing, renal tubular transporter/channel regulation affecting blood pressure, endothelial Ca2+/NO responses in microvessels, and CNS cardiometabolic control, with strong translational linkage to ARB pharmacology and emerging biased-ligand strategies. (cui2023theroleof pages 7-13, singh2024implicationsofβarrestin pages 1-3, duan2024roleofangiotensin pages 1-3, calderon2024angiotensiniidirectly pages 1-2, balapattabi2023angiotensinat1areceptor pages 1-3)

Evidence map (compact)

Category	Key points	Representative recent sources with year + DOI URL
identity	• Agtr1a encodes the mouse angiotensin II type 1a receptor (AT1aR/AT1A), a rhodopsin-like 7-transmembrane GPCR in the AT1 receptor family. • It is described as the main/major murine AT1 isoform and the mouse homolog corresponding to the single human AGTR1 gene. • Rodents express AT1a and AT1b isoforms; Agtr1a is emphasized as the dominant isoform for several renal/vascular responses, whereas Agtr1b loss does not reproduce key Agtr1a phenotypes in some vascular beds. (cui2023theroleof pages 40-41, cui2023theroleof pages 7-13, alhajoj2024assessingadenoviraldelivery pages 39-42, takayama2023angiotensiniitype pages 1-2)	Cui 2023, https://doi.org/10.17169/refubium-37035; Takayama et al. 2023, https://doi.org/10.1038/s41598-023-27737-7; Duan et al. 2024, https://doi.org/10.1161/hypertensionaha.123.21389
localization	• Plasma membrane receptor functioning in vascular smooth muscle cells as a mechanosensory/vasoconstrictor receptor in resistance vessels. • Also detected/functionally studied in vascular endothelial cells of kidney and brain microvessels, where Ang II evokes endothelial Ca2+ and NO responses sensitive to losartan. • Tissue-specific mouse studies localize Agtr1a function to renal proximal tubule, distal convoluted tubule/cortical collecting duct, and brain regions including the subfornical organ and AgRP neurons. (cui2023theroleof pages 40-41, duan2024roleofangiotensin pages 1-3, calderon2024angiotensiniidirectly pages 1-2, balapattabi2023angiotensinat1areceptor pages 1-3)	Calderon et al. 2024, https://doi.org/10.1161/jaha.123.033998; Duan et al. 2024, https://doi.org/10.1161/hypertensionaha.123.21389; Balapattabi et al. 2023, https://doi.org/10.1016/j.celrep.2023.112935
canonical signaling	• Canonical AT1aR signaling is primarily Gq/11-coupled: PLC activation cleaves PIP2 to IP3 + DAG, causing intracellular Ca2+ release and PKC activation. • Downstream pathways include ERK/MAPK, additional kinase cascades, and NADPH oxidase/ROS signaling linked to vasoconstriction, hypertrophy, inflammation, and remodeling. • In mouse vascular studies, myogenic constriction depended on Gq/11, while β-arrestin-biased ligands did not reproduce this response; extracellular Ca2+ removal or Gq/11 blockade abolished constriction. (cui2023theroleof pages 7-13, singh2024implicationsofβarrestin pages 1-3, nadasy2024directvasculareffects pages 1-2, cui2023theroleof pages 38-39)	Singh & Karnik 2024, https://doi.org/10.1016/j.cellsig.2024.111410; Nádasy et al. 2024, https://doi.org/10.3390/ijms26010113; Cui 2023, https://doi.org/10.17169/refubium-37035
beta-arrestin signaling	• GRK phosphorylation of the AT1 receptor C-terminus recruits β-arrestin-1/2, suppressing G-protein signaling and promoting clathrin-dependent internalization. • Internalized receptor/arrestin complexes can signal through MAPK/PI3K/ERK/AKT, with evidence for sustained endosomal/cytoplasmic ERK signaling distinct from canonical nuclear ERK outputs. • β-arrestin-biased ligands such as TRV027/TRV120027 and SII-AngII selectively engage this arm; reported outcomes are context-dependent, with both protective and maladaptive cardiovascular/renal effects described. (mathieu2024insightsintothe pages 3-4, singh2024implicationsofβarrestin pages 1-3, mathieu2024insightsintothe pages 6-8, jara2023distinctmechanismsof pages 1-3)	Mathieu et al. 2024, https://doi.org/10.1161/hypertensionaha.123.19419; Singh & Karnik 2024, https://doi.org/10.1016/j.cellsig.2024.111410; Jara et al. 2023, https://doi.org/10.1161/hypertensionaha.122.19232
key 2023-2024 primary findings	• Kidney tubule-specific Agtr1a deletion lowered systolic blood pressure, reduced NHE3 and Kir4.2 in proximal tubule, altered membrane potential, and increased cleaved γENaC plus amiloride-sensitive Na+ currents in cortical collecting duct; figure data also show reduced Agtr1a mRNA and a hypotensive phenotype. • In vivo endothelial imaging showed Ang II caused >4-fold increases in endothelial Ca2+ and >1.5-fold increases in NO signals in kidney/brain microvessels; responses were blocked by losartan and blunted in hypertension/fibrosis models. • In ApoE-null mice, Ang II induced aortic aneurysm in ~67% of males and ~13% mortality from aortic arch dissection without aneurysm; TRV027 or olmesartan prevented aneurysm-associated mortality. (duan2024roleofangiotensin pages 1-3, calderon2024angiotensiniidirectly pages 1-2, jara2023distinctmechanismsof pages 1-3, duan2024roleofangiotensin media 76ecb2b3)	Duan et al. 2024, https://doi.org/10.1161/hypertensionaha.123.21389; Calderon et al. 2024, https://doi.org/10.1161/jaha.123.033998; Jara et al. 2023, https://doi.org/10.1161/hypertensionaha.122.19232
therapeutics/applications	• ARBs such as losartan, olmesartan, and related AT1 blockers are used experimentally and clinically to suppress harmful AT1 signaling; in mouse and translational studies they reduce blood pressure and vascular pathology, and losartan blocked endothelial Ang II Ca2+/NO responses. • β-arrestin-biased agonists (especially TRV027) are being explored to preserve potentially beneficial noncanonical signaling while limiting G-protein-mediated injury; preclinical models showed lower BP, improved hemodynamics, and vascular protection, though clinical benefit has been mixed. • Agtr1a global, floxed, and cell-specific knockout mouse models are now standard real-world implementations for dissecting renal, vascular, and brain AT1a functions. (mathieu2024insightsintothe pages 6-8, mathieu2024insightsintothe pages 8-9, calderon2024angiotensiniidirectly pages 1-2, eguchi2024milestonepaperson pages 3-4)	Mathieu et al. 2024, https://doi.org/10.1161/hypertensionaha.123.19419; Calderon et al. 2024, https://doi.org/10.1161/jaha.123.033998; Eguchi et al. 2024, https://doi.org/10.1161/hypertensionaha.123.21365

Table: This table summarizes verified identity, localization, signaling mechanisms, recent primary findings, and translational applications for mouse Agtr1a/AT1aR. It is useful as a compact evidence-backed functional annotation derived only from sources gathered in this chat.

References

(cui2023theroleof pages 7-13): Yingqiu Cui. The role of angiotensin ii type 1a receptor and downstream signaling in murine myogenic vasoconstriction. Text, Jan 2023. URL: https://doi.org/10.17169/refubium-37035, doi:10.17169/refubium-37035. This article has 0 citations and is from a peer-reviewed journal.
(takayama2023angiotensiniitype pages 1-2): Suguru Takayama, Kazuho Inoue, Yuji Ogura, Seiko Hoshino, Takeshi Sugaya, Keiichi Ohata, Hitoshi Kotake, Daisuke Ichikawa, Minoru Watanabe, Kenjiro Kimura, Yugo Shibagaki, and Atsuko Kamijo-Ikemori. Angiotensin ii type 1a receptor deficiency alleviates muscle atrophy after denervation. Scientific Reports, Jan 2023. URL: https://doi.org/10.1038/s41598-023-27737-7, doi:10.1038/s41598-023-27737-7. This article has 4 citations and is from a peer-reviewed journal.
(alhajoj2024assessingadenoviraldelivery pages 39-42): AMA Alhajoj. Assessing adenoviral delivery of prolylcarboxypeptidase and extracellular vesicle-mediated delivery of angiotensin converting enzyme 2 as therapies in hypertensive …. Unknown journal, 2024.
(nadasy2024directvasculareffects pages 1-2): György L. Nádasy, András Balla, Gabriella Dörnyei, László Hunyady, and Mária Szekeres. Direct vascular effects of angiotensin ii (a systematic short review). International Journal of Molecular Sciences, 26:113, Dec 2024. URL: https://doi.org/10.3390/ijms26010113, doi:10.3390/ijms26010113. This article has 31 citations.
(singh2024implicationsofβarrestin pages 1-3): Khuraijam Dhanachandra Singh and Sadashiva S. Karnik. Implications of β-arrestin biased signaling by angiotensin ii type 1 receptor for cardiovascular drug discovery and therapeutics. Cellular Signalling, 124:111410, Dec 2024. URL: https://doi.org/10.1016/j.cellsig.2024.111410, doi:10.1016/j.cellsig.2024.111410. This article has 11 citations and is from a peer-reviewed journal.
(mathieu2024insightsintothe pages 3-4): Natalia M. Mathieu, Pablo Nakagawa, Justin L. Grobe, and Curt D. Sigmund. Insights into the role of angiotensin-ii at ₁ receptor-dependent β-arrestin signaling in cardiovascular disease. Hypertension, 81:6-16, Jan 2024. URL: https://doi.org/10.1161/hypertensionaha.123.19419, doi:10.1161/hypertensionaha.123.19419. This article has 30 citations and is from a domain leading peer-reviewed journal.
(cui2023theroleof pages 40-41): Yingqiu Cui. The role of angiotensin ii type 1a receptor and downstream signaling in murine myogenic vasoconstriction. Text, Jan 2023. URL: https://doi.org/10.17169/refubium-37035, doi:10.17169/refubium-37035. This article has 0 citations and is from a peer-reviewed journal.
(calderon2024angiotensiniidirectly pages 1-2): Alejandra Becerra Calderon, Urvi Nikhil Shroff, Sachin Deepak, Audrey Izuhara, Greta Trogen, Alicia A. McDonough, Susan B. Gurley, Jonathan W. Nelson, János Peti‐Peterdi, and Georgina Gyarmati. Angiotensin ii directly increases endothelial calcium and nitric oxide in kidney and brain microvessels in vivo with reduced efficacy in hypertension. Journal of the American Heart Association, May 2024. URL: https://doi.org/10.1161/jaha.123.033998, doi:10.1161/jaha.123.033998. This article has 14 citations.
(duan2024roleofangiotensin pages 1-3): Xin-Peng Duan, Yu Xiao, Xiao-Tong Su, Jun-Ya Zheng, Susan Gurley, Jacqueline Emathinger, Chao-Ling Yang, James McCormick, David H. Ellison, Dao-Hong Lin, and Wen-Hui Wang. Role of angiotensin ii type 1a receptor (at1ar) of renal tubules in regulating inwardly rectifying potassium channels 4.2 (kir4.2), kir4.1, and epithelial na ⁺ channel (enac). Hypertension, 81:126-137, Jan 2024. URL: https://doi.org/10.1161/hypertensionaha.123.21389, doi:10.1161/hypertensionaha.123.21389. This article has 7 citations and is from a domain leading peer-reviewed journal.
(balapattabi2023angiotensinat1areceptor pages 1-3): Kirthikaa Balapattabi, Yavuz Yavuz, Jingwei Jiang, Guorui Deng, Natalia M. Mathieu, McKenzie L. Ritter, Megan A. Opichka, John J. Reho, John D. McCorvy, Pablo Nakagawa, Lisa L. Morselli, Gary C. Mouradian, Deniz Atasoy, Huxing Cui, Matthew R. Hodges, Curt D. Sigmund, and Justin L. Grobe. Angiotensin at1a receptor signal switching in agouti-related peptide neurons mediates metabolic rate adaptation during obesity. Cell reports, 42:112935-112935, Aug 2023. URL: https://doi.org/10.1016/j.celrep.2023.112935, doi:10.1016/j.celrep.2023.112935. This article has 15 citations and is from a highest quality peer-reviewed journal.
(jara2023distinctmechanismsof pages 1-3): Zaira Palomino Jara, Terri J. Harford, Khuraijam Dhanachandra Singh, Russell Desnoyer, Avinash Kumar, Dasarathy Srinivasan, and Sadashiva S. Karnik. Distinct mechanisms of β-arrestin–biased agonist and blocker of at1r in preventing aortic aneurysm and associated mortality. Hypertension, 80:385-402, Feb 2023. URL: https://doi.org/10.1161/hypertensionaha.122.19232, doi:10.1161/hypertensionaha.122.19232. This article has 23 citations and is from a domain leading peer-reviewed journal.
(jara2023distinctmechanismsof pages 14-15): Zaira Palomino Jara, Terri J. Harford, Khuraijam Dhanachandra Singh, Russell Desnoyer, Avinash Kumar, Dasarathy Srinivasan, and Sadashiva S. Karnik. Distinct mechanisms of β-arrestin–biased agonist and blocker of at1r in preventing aortic aneurysm and associated mortality. Hypertension, 80:385-402, Feb 2023. URL: https://doi.org/10.1161/hypertensionaha.122.19232, doi:10.1161/hypertensionaha.122.19232. This article has 23 citations and is from a domain leading peer-reviewed journal.
(eguchi2024milestonepaperson pages 3-4): Satoru Eguchi, Keiichi Torimoto, Adebowale Adebiyi, Praghalathan Kanthakumar, Gisele F. Bomfim, Camilla Ferreira Wenceslau, Shelby A. Dahlen, and Patrick Osei-Owusu. Milestone papers on signal transduction mechanisms of hypertension and its complications. Hypertension, 81:977-990, May 2024. URL: https://doi.org/10.1161/hypertensionaha.123.21365, doi:10.1161/hypertensionaha.123.21365. This article has 6 citations and is from a domain leading peer-reviewed journal.
(mathieu2024insightsintothe pages 6-8): Natalia M. Mathieu, Pablo Nakagawa, Justin L. Grobe, and Curt D. Sigmund. Insights into the role of angiotensin-ii at ₁ receptor-dependent β-arrestin signaling in cardiovascular disease. Hypertension, 81:6-16, Jan 2024. URL: https://doi.org/10.1161/hypertensionaha.123.19419, doi:10.1161/hypertensionaha.123.19419. This article has 30 citations and is from a domain leading peer-reviewed journal.
(singh2024implicationsofβarrestin pages 3-5): Khuraijam Dhanachandra Singh and Sadashiva S. Karnik. Implications of β-arrestin biased signaling by angiotensin ii type 1 receptor for cardiovascular drug discovery and therapeutics. Cellular Signalling, 124:111410, Dec 2024. URL: https://doi.org/10.1016/j.cellsig.2024.111410, doi:10.1016/j.cellsig.2024.111410. This article has 11 citations and is from a peer-reviewed journal.
(duan2024roleofangiotensin media 76ecb2b3): Xin-Peng Duan, Yu Xiao, Xiao-Tong Su, Jun-Ya Zheng, Susan Gurley, Jacqueline Emathinger, Chao-Ling Yang, James McCormick, David H. Ellison, Dao-Hong Lin, and Wen-Hui Wang. Role of angiotensin ii type 1a receptor (at1ar) of renal tubules in regulating inwardly rectifying potassium channels 4.2 (kir4.2), kir4.1, and epithelial na ⁺ channel (enac). Hypertension, 81:126-137, Jan 2024. URL: https://doi.org/10.1161/hypertensionaha.123.21389, doi:10.1161/hypertensionaha.123.21389. This article has 7 citations and is from a domain leading peer-reviewed journal.
(duan2024roleofangiotensin media b9bb5956): Xin-Peng Duan, Yu Xiao, Xiao-Tong Su, Jun-Ya Zheng, Susan Gurley, Jacqueline Emathinger, Chao-Ling Yang, James McCormick, David H. Ellison, Dao-Hong Lin, and Wen-Hui Wang. Role of angiotensin ii type 1a receptor (at1ar) of renal tubules in regulating inwardly rectifying potassium channels 4.2 (kir4.2), kir4.1, and epithelial na ⁺ channel (enac). Hypertension, 81:126-137, Jan 2024. URL: https://doi.org/10.1161/hypertensionaha.123.21389, doi:10.1161/hypertensionaha.123.21389. This article has 7 citations and is from a domain leading peer-reviewed journal.
(duan2024roleofangiotensin media baf624f1): Xin-Peng Duan, Yu Xiao, Xiao-Tong Su, Jun-Ya Zheng, Susan Gurley, Jacqueline Emathinger, Chao-Ling Yang, James McCormick, David H. Ellison, Dao-Hong Lin, and Wen-Hui Wang. Role of angiotensin ii type 1a receptor (at1ar) of renal tubules in regulating inwardly rectifying potassium channels 4.2 (kir4.2), kir4.1, and epithelial na ⁺ channel (enac). Hypertension, 81:126-137, Jan 2024. URL: https://doi.org/10.1161/hypertensionaha.123.21389, doi:10.1161/hypertensionaha.123.21389. This article has 7 citations and is from a domain leading peer-reviewed journal.
(cui2023theroleof pages 38-39): Yingqiu Cui. The role of angiotensin ii type 1a receptor and downstream signaling in murine myogenic vasoconstriction. Text, Jan 2023. URL: https://doi.org/10.17169/refubium-37035, doi:10.17169/refubium-37035. This article has 0 citations and is from a peer-reviewed journal.
(mathieu2024insightsintothe pages 8-9): Natalia M. Mathieu, Pablo Nakagawa, Justin L. Grobe, and Curt D. Sigmund. Insights into the role of angiotensin-ii at ₁ receptor-dependent β-arrestin signaling in cardiovascular disease. Hypertension, 81:6-16, Jan 2024. URL: https://doi.org/10.1161/hypertensionaha.123.19419, doi:10.1161/hypertensionaha.123.19419. This article has 30 citations and is from a domain leading peer-reviewed journal.

Citations

nadasy2024directvasculareffects pages 1-2
mathieu2024insightsintothe pages 3-4
calderon2024angiotensiniidirectly pages 1-2
duan2024roleofangiotensin pages 1-3
jara2023distinctmechanismsof pages 1-3
eguchi2024milestonepaperson pages 3-4
mathieu2024insightsintothe pages 6-8
cui2023theroleof pages 7-13
takayama2023angiotensiniitype pages 1-2
alhajoj2024assessingadenoviraldelivery pages 39-42
cui2023theroleof pages 40-41
jara2023distinctmechanismsof pages 14-15
cui2023theroleof pages 38-39
mathieu2024insightsintothe pages 8-9
https://doi.org/10.1161/hypertensionaha.123.21365
https://doi.org/10.1161/hypertensionaha.123.19419
https://doi.org/10.1016/j.cellsig.2024.111410
https://doi.org/10.1161/jaha.123.033998
https://doi.org/10.1161/hypertensionaha.122.19232
https://doi.org/10.1161/hypertensionaha.123.21389
https://doi.org/10.3390/ijms26010113
https://doi.org/10.17169/refubium-37035;
https://doi.org/10.1038/s41598-023-27737-7;
https://doi.org/10.1161/jaha.123.033998;
https://doi.org/10.1161/hypertensionaha.123.21389;
https://doi.org/10.1016/j.celrep.2023.112935
https://doi.org/10.1016/j.cellsig.2024.111410;
https://doi.org/10.3390/ijms26010113;
https://doi.org/10.17169/refubium-37035
https://doi.org/10.1161/hypertensionaha.123.19419;
https://doi.org/10.17169/refubium-37035,
https://doi.org/10.1038/s41598-023-27737-7,
https://doi.org/10.3390/ijms26010113,
https://doi.org/10.1016/j.cellsig.2024.111410,
https://doi.org/10.1161/hypertensionaha.123.19419,
https://doi.org/10.1161/jaha.123.033998,
https://doi.org/10.1161/hypertensionaha.123.21389,
https://doi.org/10.1016/j.celrep.2023.112935,
https://doi.org/10.1161/hypertensionaha.122.19232,
https://doi.org/10.1161/hypertensionaha.123.21365,

Notes

(Agtr1a-notes.md)

Agtr1a curation notes

Evidence synthesis

Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity. UniProt summarizes the function as: "Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney." [file:mouse/Agtr1a/Agtr1a-uniprot.txt]
Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations." This supports angiotensin-activated GPCR signaling, phospholipase C signaling, and calcium mobilization as direct pathway outputs. [file:mouse/Agtr1a/Agtr1a-uniprot.txt]
Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan. [PMID:12657564 "A role for angiotensin II AT1 receptors in ureteric bud cell branching.", "cultured murine UB cells express AT1 receptor protein and mRNA ... ANG II ... elicits a dose-related increase in the number of cells that have primary and secondary branches"]
Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship. This supports non-core organismal annotations for renal output, aldosterone regulation, salt-sensitive blood pressure, and drinking/volume phenotypes. [PMID:12167595 "Effects of AT(1A) receptor deletion on blood pressure and sodium excretion during altered dietary salt intake.", "high urinary volume and low blood pressure despite increased renin and aldosterone levels"]
Mouse AT1 receptor redundancy and blood-pressure/kidney phenotypes: Agtr1a/Agtr1b double mutants have "marked hypotension, and abnormal kidney morphology including delayed maturity in glomerular growth, hypoplastic papilla, and renal arterial hypertrophy." This supports AT1 receptor involvement in blood pressure and renal development but does not make broad developmental terms the core molecular function. [PMID:9466969 "Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes.", "marked hypotension, and abnormal kidney morphology including delayed maturity in glomerular growth, hypoplastic papilla, and renal arterial hypertrophy"]
Brain and drinking behavior: Central angiotensin II experiments show that "the blood pressure increase elicited by centrally administered angiotensin II can be selectively ascribed to the AT(1A) receptor" while drinking depends more on AT1B. This supports keeping brain renin-angiotensin and drinking terms as non-core or qualified phenotypes, not core receptor function. [PMID:10880053 "Divergent functions of angiotensin II receptor isoforms in the brain.", "the blood pressure increase elicited by centrally administered angiotensin II can be selectively ascribed to the AT(1A) receptor"]
Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation. A later study reports that ATRAP "significantly promotes downregulation of the AT1R." These support receptor trafficking/regulation annotations but the GO term protein binding remains too vague for curation. [PMID:10358057 "Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor.", "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"] [PMID:15757644 "The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy.", "significantly promotes downregulation of the AT1R"]
Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling. They should be kept only as non-core when directly supported by mouse evidence, otherwise marked as over-annotated or removed in favor of the specific receptor/signaling terms.
Falcon integration: the Falcon report reinforces the same core model: "Agtr1a encodes a cell-surface receptor whose primary function is to bind Ang II and transduce signals through" canonical Gq/PLC/calcium signaling and beta-arrestin-dependent receptor trafficking. It also adds recent 2023-2024 mouse literature on vascular mechanosensing, renal tubular Agtr1a deletion, and endothelial calcium/NO signaling, which supports keeping broad vascular/renal phenotypes as non-core context rather than expanding the core function. [file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md]

📄 View Raw YAML

id: P29754
gene_symbol: Agtr1a
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: 'Agtr1a encodes the mouse angiotensin II type 1A receptor, a rhodopsin-family GPCR for angiotensin II. The receptor signals mainly through Gq/phospholipase C and calcium mobilization at the plasma membrane and mediates major renin-angiotensin outputs including vasoconstriction, renal sodium/water handling, aldosterone regulation, and blood-pressure control.'
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0001822
    label: kidney development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: kidney development is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.'
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: regulation of blood pressure is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0038166
    label: angiotensin-activated signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0007204
    label: positive regulation of cytosolic calcium ion concentration
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: positive regulation of cytosolic calcium ion concentration is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0001596
    label: angiotensin type I receptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by IBA evidence (GO_REF:0000033).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0006954
    label: inflammatory response
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: inflammatory response is a broad downstream phenotype and is not
      directly established as an Agtr1a-specific annotation by the reviewed evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: The curated model is better captured by AT1A receptor activity,
      angiotensin-activated PLC/calcium signaling, and renal/vascular blood-pressure
      terms rather than a generic inflammatory-response transfer.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0003081
    label: regulation of systemic arterial blood pressure by renin-angiotensin
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: regulation of systemic arterial blood pressure by renin-angiotensin is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0004930
    label: G protein-coupled receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: G protein-coupled receptor activity captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin type I receptor activity for this gene. Replace with angiotensin type I receptor activity to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0001596
      label: angiotensin type I receptor activity
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0004945
    label: angiotensin type II receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: angiotensin type II receptor activity captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin type I receptor activity for this gene. Replace with angiotensin type I receptor activity to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0001596
      label: angiotensin type I receptor activity
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IEA evidence (GO_REF:0000120).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: signal transduction captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0038166
      label: angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0038166
      label: angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: membrane is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0019229
    label: regulation of vasoconstriction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: regulation of vasoconstriction captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0042310
      label: vasoconstriction
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10358057
  review:
    summary: protein binding is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15757644
  review:
    summary: protein binding is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0001596
    label: angiotensin type I receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by IEA evidence (GO_REF:0000107).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0001921
    label: positive regulation of receptor recycling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of receptor recycling is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0002018
    label: renin-angiotensin regulation of aldosterone production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: renin-angiotensin regulation of aldosterone production is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: The local evidence supports Agtr1a as a plasma-membrane GPCR but
      does not verify Golgi localization.
    action: UNDECIDED
    reason: The previous support text described renal blood-pressure physiology
      and did not justify this specific cellular-component annotation.
- term:
    id: GO:0006885
    label: regulation of pH
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of pH is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0007200
    label: phospholipase C-activating G protein-coupled receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: phospholipase C-activating G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than phospholipase C-activating angiotensin-activated signaling pathway for this gene. Replace with phospholipase C-activating angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0086097
      label: phospholipase C-activating angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cell population proliferation is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0009651
    label: response to salt stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to salt stress is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0014823
    label: response to activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to activity is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: basolateral plasma membrane is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein kinase binding is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: The local evidence supports brain/CNS roles for Agtr1a but does
      not verify dendrite localization.
    action: UNDECIDED
    reason: Retaining this cellular-component annotation requires direct
      localization evidence rather than renal or blood-pressure physiology.
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cytoplasmic vesicle is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0031748
    label: D1 dopamine receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: D1 dopamine receptor binding is not supported as an Agtr1a annotation
      by the reviewed mouse evidence.
    action: REMOVE
    reason: The available evidence supports AT1A angiotensin receptor activity;
      dopamine receptor papers do not establish direct Agtr1a-D1 receptor binding.
- term:
    id: GO:0031968
    label: organelle outer membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: organelle outer membrane is not supported as an appropriate annotation for Agtr1a after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Agtr1a biology.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0032930
    label: positive regulation of superoxide anion generation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of superoxide anion generation is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0038166
    label: angiotensin-activated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by IEA evidence (GO_REF:0000107).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0042310
    label: vasoconstriction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: vasoconstriction is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0042416
    label: dopamine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: dopamine biosynthetic process is not supported as an appropriate annotation for Agtr1a after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Agtr1a biology.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0042756
    label: drinking behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Drinking behavior is not supported as an Agtr1a-specific annotation
      by the reviewed mouse evidence.
    action: REMOVE
    reason: Direct central angiotensin II experiments separate AT1A-dependent
      blood-pressure responses from drinking behavior, which requires AT1B.
    supported_by:
    - reference_id: PMID:10880053
      supporting_text: the drinking response requires the presence of AT(1B) receptors.
- term:
    id: GO:0043627
    label: response to estrogen
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to estrogen is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0045766
    label: positive regulation of angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of angiogenesis is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0045777
    label: positive regulation of blood pressure
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of blood pressure is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0051412
    label: response to corticosterone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to corticosterone is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: recycling endosome is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0071549
    label: cellular response to dexamethasone stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to dexamethasone stimulus is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0090190
    label: positive regulation of branching involved in ureteric bud morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of branching involved in ureteric bud morphogenesis is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.'
- term:
    id: GO:1905665
    label: positive regulation of calcium ion import across plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of calcium ion import across plasma membrane is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:1990776
    label: response to angiotensin
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to angiotensin captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0038166
      label: angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0042976
    label: activation of Janus kinase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: activation of Janus kinase activity is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0001596
    label: angiotensin type I receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0001596
    label: angiotensin type I receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0001822
    label: kidney development
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: kidney development is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.'
- term:
    id: GO:0001921
    label: positive regulation of receptor recycling
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of receptor recycling is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0002018
    label: renin-angiotensin regulation of aldosterone production
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: renin-angiotensin regulation of aldosterone production is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0002034
    label: maintenance of blood vessel diameter homeostasis by renin-angiotensin
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: maintenance of blood vessel diameter homeostasis by renin-angiotensin is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0004945
    label: angiotensin type II receptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: angiotensin type II receptor activity captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin type I receptor activity for this gene. Replace with angiotensin type I receptor activity to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0001596
      label: angiotensin type I receptor activity
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: The local evidence supports Agtr1a as a plasma-membrane GPCR but
      does not verify Golgi localization.
    action: UNDECIDED
    reason: The previous support text described renal blood-pressure physiology
      and did not justify this specific cellular-component annotation.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0006885
    label: regulation of pH
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of pH is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0038166
      label: angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0038166
      label: angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0007200
    label: phospholipase C-activating G protein-coupled receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: phospholipase C-activating G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than phospholipase C-activating angiotensin-activated signaling pathway for this gene. Replace with phospholipase C-activating angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0086097
      label: phospholipase C-activating angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0007200
    label: phospholipase C-activating G protein-coupled receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: phospholipase C-activating G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than phospholipase C-activating angiotensin-activated signaling pathway for this gene. Replace with phospholipase C-activating angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0086097
      label: phospholipase C-activating angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0007204
    label: positive regulation of cytosolic calcium ion concentration
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cytosolic calcium ion concentration is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0007266
    label: Rho protein signal transduction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Rho protein signal transduction is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cell population proliferation is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0010744
    label: positive regulation of macrophage derived foam cell differentiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of macrophage derived foam cell differentiation is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: basolateral plasma membrane is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0019229
    label: regulation of vasoconstriction
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: regulation of vasoconstriction captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0042310
      label: vasoconstriction
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0019722
    label: calcium-mediated signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: calcium-mediated signaling is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein kinase binding is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: The local evidence supports brain/CNS roles for Agtr1a but does
      not verify dendrite localization.
    action: UNDECIDED
    reason: Retaining this cellular-component annotation requires direct
      localization evidence rather than renal or blood-pressure physiology.
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cytoplasmic vesicle is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0031711
    label: bradykinin receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: bradykinin receptor binding is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0031748
    label: D1 dopamine receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: D1 dopamine receptor binding is not supported as an Agtr1a annotation
      by the reviewed mouse evidence.
    action: REMOVE
    reason: The available evidence supports AT1A angiotensin receptor activity;
      dopamine receptor papers do not establish direct Agtr1a-D1 receptor binding.
- term:
    id: GO:0031968
    label: organelle outer membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: organelle outer membrane is not supported as an appropriate annotation for Agtr1a after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Agtr1a biology.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0032930
    label: positive regulation of superoxide anion generation
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of superoxide anion generation is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0038166
    label: angiotensin-activated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000096).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0038166
    label: angiotensin-activated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0042310
    label: vasoconstriction
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: vasoconstriction is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0042416
    label: dopamine biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: dopamine biosynthetic process is not supported as an appropriate annotation for Agtr1a after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Agtr1a biology.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0042756
    label: drinking behavior
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Drinking behavior is not supported as an Agtr1a-specific annotation
      by the reviewed mouse evidence.
    action: REMOVE
    reason: Direct central angiotensin II experiments separate AT1A-dependent
      blood-pressure responses from drinking behavior, which requires AT1B.
    supported_by:
    - reference_id: PMID:10880053
      supporting_text: the drinking response requires the presence of AT(1B) receptors.
- term:
    id: GO:0043627
    label: response to estrogen
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: response to estrogen is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0045766
    label: positive regulation of angiogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of angiogenesis is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0045777
    label: positive regulation of blood pressure
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of blood pressure is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0046718
    label: symbiont entry into host cell
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: symbiont entry into host cell is not supported as an appropriate annotation for Agtr1a after review of the available mouse evidence.
    action: REMOVE
    reason: The term appears to reflect either an unsupported transfer, a paralog/family overreach, or a localization/process inconsistent with the curated Agtr1a biology.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0046982
    label: protein heterodimerization activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein heterodimerization activity is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0055037
    label: recycling endosome
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: recycling endosome is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0060326
    label: cell chemotaxis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cell chemotaxis is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0071549
    label: cellular response to dexamethasone stimulus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cellular response to dexamethasone stimulus is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0086097
    label: phospholipase C-activating angiotensin-activated signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: phospholipase C-activating angiotensin-activated signaling pathway is biologically consistent with the curated synthesis for Agtr1a and is supported by ISO evidence (GO_REF:0000119).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
- term:
    id: GO:0090190
    label: positive regulation of branching involved in ureteric bud morphogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of branching involved in ureteric bud morphogenesis is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.'
- term:
    id: GO:0090205
    label: positive regulation of cholesterol metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of cholesterol metabolic process is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:1903589
    label: positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:1905665
    label: positive regulation of calcium ion import across plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of calcium ion import across plasma membrane is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0010467
    label: gene expression
  evidence_type: IMP
  original_reference_id: PMID:24206662
  review:
    summary: gene expression is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0002034
    label: maintenance of blood vessel diameter homeostasis by renin-angiotensin
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: maintenance of blood vessel diameter homeostasis by renin-angiotensin is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0008217
    label: regulation of blood pressure
  evidence_type: IMP
  original_reference_id: PMID:26531127
  review:
    summary: regulation of blood pressure is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0006954
    label: inflammatory response
  evidence_type: IGI
  original_reference_id: PMID:19404405
  review:
    summary: This paper supports Mas/Ang-(1-7)-dependent renal inflammation, not
      an Agtr1a-specific inflammatory response.
    action: REMOVE
    reason: The cited study explicitly shows the inflammatory effect is preserved
      when Ang II receptors are absent, so it should not be retained for Agtr1a.
    supported_by:
    - reference_id: PMID:19404405
      supporting_text: showing that this effect is AT1 and AT2 independent
- term:
    id: GO:0034391
    label: regulation of smooth muscle cell apoptotic process
  evidence_type: IGI
  original_reference_id: PMID:19508861
  review:
    summary: regulation of smooth muscle cell apoptotic process is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0034392
    label: negative regulation of smooth muscle cell apoptotic process
  evidence_type: IMP
  original_reference_id: PMID:19508861
  review:
    summary: negative regulation of smooth muscle cell apoptotic process is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:19508861
  review:
    summary: positive regulation of cell population proliferation is related to reported Agtr1a biology only as a broad downstream readout or generic interaction term.
    action: MARK_AS_OVER_ANNOTATED
    reason: This overstates the direct role of the gene product; the curated model is better captured by the specific receptor/ligand, pathway, and supported non-core phenotype terms.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Curation judgment: terms that describe broad responses to hormones, salt, activity, estrogen, corticosterone, dexamethasone, or generic cell proliferation/inflammation are generally downstream, context-specific phenotypes of angiotensin signaling.'
- term:
    id: GO:0002035
    label: brain renin-angiotensin system
  evidence_type: IMP
  original_reference_id: PMID:16585392
  review:
    summary: brain renin-angiotensin system is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IMP
  original_reference_id: PMID:16585392
  review:
    summary: heart development is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0001819
    label: positive regulation of cytokine production
  evidence_type: IMP
  original_reference_id: PMID:19023134
  review:
    summary: positive regulation of cytokine production is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0045777
    label: positive regulation of blood pressure
  evidence_type: IMP
  original_reference_id: PMID:12486173
  review:
    summary: This dopamine D5 receptor paper does not establish a direct Agtr1a
      positive regulation of blood pressure annotation.
    action: REMOVE
    reason: Other direct Agtr1a blood-pressure annotations are retained, but this
      source-specific row is based on a dopamine receptor knockout study rather
      than Agtr1a function.
    supported_by:
    - reference_id: PMID:12486173
      supporting_text: Mice lacking D5 dopamine receptors have increased sympathetic
        tone and are hypertensive.
- term:
    id: GO:0045777
    label: positive regulation of blood pressure
  evidence_type: IGI
  original_reference_id: PMID:9691085
  review:
    summary: This dopamine D3 receptor paper does not establish a direct Agtr1a
      positive regulation of blood pressure annotation.
    action: REMOVE
    reason: Other direct Agtr1a blood-pressure annotations are retained, but this
      source-specific row is based on a dopamine receptor knockout study rather
      than Agtr1a function.
    supported_by:
    - reference_id: PMID:9691085
      supporting_text: disruption of the D3 receptor, a member of the family of
        D2-like receptors
- term:
    id: GO:0045777
    label: positive regulation of blood pressure
  evidence_type: IDA
  original_reference_id: PMID:12486173
  review:
    summary: This dopamine D5 receptor paper does not establish a direct Agtr1a
      positive regulation of blood pressure annotation.
    action: REMOVE
    reason: Other direct Agtr1a blood-pressure annotations are retained, but this
      source-specific row is based on a dopamine receptor knockout study rather
      than Agtr1a function.
    supported_by:
    - reference_id: PMID:12486173
      supporting_text: Mice lacking D5 dopamine receptors have increased sympathetic
        tone and are hypertensive.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15499027
  review:
    summary: The cited cerebral microvessel paper supports AT1 localization in
      vascular cells but does not verify cytoplasm as the appropriate component.
    action: UNDECIDED
    reason: Agtr1a is retained as a membrane GPCR; a cytoplasm annotation needs
      term-specific localization evidence rather than vascular physiology.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:15499027
  review:
    summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IDA evidence (PMID:15499027).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0001568
    label: blood vessel development
  evidence_type: IGI
  original_reference_id: PMID:9466969
  review:
    summary: blood vessel development is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0001822
    label: kidney development
  evidence_type: IMP
  original_reference_id: PMID:12167595
  review:
    summary: kidney development is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.'
- term:
    id: GO:0001822
    label: kidney development
  evidence_type: IGI
  original_reference_id: PMID:9466969
  review:
    summary: kidney development is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse kidney-development evidence: Iosipiv and Schroeder report that "cultured murine UB cells express AT1 receptor protein and mRNA" and that ANG II treatment "elicits a dose-related increase in the number of cells that have primary and secondary branches"; the effect is blocked by the AT1 antagonist candesartan.'
- term:
    id: GO:0001991
    label: regulation of systemic arterial blood pressure by circulatory renin-angiotensin
  evidence_type: IGI
  original_reference_id: PMID:9466969
  review:
    summary: regulation of systemic arterial blood pressure by circulatory renin-angiotensin is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0002001
    label: renin secretion into blood stream
  evidence_type: IMP
  original_reference_id: PMID:12167595
  review:
    summary: renin secretion into blood stream is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0002018
    label: renin-angiotensin regulation of aldosterone production
  evidence_type: IMP
  original_reference_id: PMID:12167595
  review:
    summary: renin-angiotensin regulation of aldosterone production is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0002019
    label: regulation of renal output by angiotensin
  evidence_type: IMP
  original_reference_id: PMID:12167595
  review:
    summary: regulation of renal output by angiotensin is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Mouse renal and blood-pressure physiology: AT1A-deficient mice on altered salt diets show "high urinary volume and low blood pressure despite increased renin and aldosterone levels" and a shifted pressure-natriuresis relationship.'
- term:
    id: GO:0042756
    label: drinking behavior
  evidence_type: IMP
  original_reference_id: PMID:12167595
  review:
    summary: This renal sodium-balance paper does not support drinking behavior
      as an Agtr1a-specific annotation.
    action: REMOVE
    reason: The cited study supports renal output and blood-pressure physiology;
      direct central angiotensin II evidence instead assigns drinking behavior
      primarily to AT1B rather than AT1A.
    supported_by:
    - reference_id: PMID:12167595
      supporting_text: These studies demonstrate that mice lacking the AT(1A)
        receptor have blood pressures sensitive to changes in dietary sodium
- term:
    id: GO:0001596
    label: angiotensin type I receptor activity
  evidence_type: IDA
  original_reference_id: PMID:12657564
  review:
    summary: angiotensin type I receptor activity is biologically consistent with the curated synthesis for Agtr1a and is supported by IDA evidence (PMID:12657564).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
    - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
      supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
- term:
    id: GO:0002035
    label: brain renin-angiotensin system
  evidence_type: IMP
  original_reference_id: PMID:10880053
  review:
    summary: brain renin-angiotensin system is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: PMID:10880053
      supporting_text: AT(1A) expression generally exceeding AT(1B) expression
- term:
    id: GO:0042756
    label: drinking behavior
  evidence_type: IMP
  original_reference_id: PMID:10880053
  review:
    summary: Drinking behavior is not supported as an Agtr1a-specific annotation
      by this direct central angiotensin II study.
    action: REMOVE
    reason: The same citation explicitly separates AT1A-dependent blood-pressure
      responses from drinking behavior, which requires AT1B.
    supported_by:
    - reference_id: PMID:10880053
      supporting_text: the drinking response requires the presence of AT(1B) receptors.
- term:
    id: GO:0042756
    label: drinking behavior
  evidence_type: IGI
  original_reference_id: PMID:10880053
  review:
    summary: Drinking behavior is not supported as an Agtr1a-specific annotation
      by this direct central angiotensin II study.
    action: REMOVE
    reason: The same citation explicitly separates AT1A-dependent blood-pressure
      responses from drinking behavior, which requires AT1B.
    supported_by:
    - reference_id: PMID:10880053
      supporting_text: the drinking response requires the presence of AT(1B) receptors.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:14718562
  review:
    summary: endosome is supported for Agtr1a in a tissue, developmental, trafficking, or disease-model context, but it is not the core molecular role.
    action: KEEP_AS_NON_CORE
    reason: This annotation captures a real downstream or context-specific consequence of Agtr1a activity. It should be retained as non-core so it does not obscure the primary receptor/ligand signaling function.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Trafficking and protein-interaction evidence: ATRAP was isolated using the cytoplasmic domain of murine AT1A and "interacts specifically with the carboxyl-terminal domain of the AT1a receptor"; overexpression inhibits AT1A-mediated PLC activation.'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:14718562
  review:
    summary: plasma membrane is biologically consistent with the curated synthesis for Agtr1a and is supported by IDA evidence (PMID:14718562).
    action: ACCEPT
    reason: The term matches a direct molecular function, pathway, or location/physiological output of Agtr1a; it is specific enough to retain without replacement.
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
- term:
    id: GO:0007186
    label: G protein-coupled receptor signaling pathway
  evidence_type: IC
  original_reference_id: PMID:12657564
  review:
    summary: G protein-coupled receptor signaling pathway captures the right general biology for Agtr1a, but a more specific GO term is available.
    action: MODIFY
    reason: The current term is too broad or less precise than angiotensin-activated signaling pathway for this gene. Replace with angiotensin-activated signaling pathway to align the annotation with the reviewed evidence.
    proposed_replacement_terms:
    - id: GO:0038166
      label: angiotensin-activated signaling pathway
    supported_by:
    - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
      supporting_text: 'Core signaling: UniProt states that activated AGTR1A "couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations."'
references:
- id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
  title: Falcon deep research report for mouse Agtr1a
- id: file:mouse/Agtr1a/Agtr1a-notes.md
  title: Curator notes for mouse Agtr1a review
- id: file:mouse/Agtr1a/Agtr1a-uniprot.txt
  title: UniProtKB record for mouse Agtr1a
- id: file:mouse/Agtr1a/Agtr1a-goa.tsv
  title: QuickGO export for mouse Agtr1a
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10358057
  title: Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor.
  findings: []
- id: PMID:10880053
  title: Divergent functions of angiotensin II receptor isoforms in the brain.
  findings: []
- id: PMID:12167595
  title: Effects of AT(1A) receptor deletion on blood pressure and sodium excretion during altered dietary salt intake.
  findings: []
- id: PMID:12486173
  title: Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive.
  findings: []
- id: PMID:12657564
  title: A role for angiotensin II AT1 receptors in ureteric bud cell branching.
  findings: []
- id: PMID:14718562
  title: Phospholipase D2 localizes to the plasma membrane and regulates angiotensin II receptor endocytosis.
  findings: []
- id: PMID:15499027
  title: Angiotensin II impairs neurovascular coupling in neocortex through NADPH oxidase-derived radicals.
  findings: []
- id: PMID:15757644
  title: The novel angiotensin II type 1 receptor (AT1R)-associated protein ATRAP downregulates AT1R and ameliorates cardiomyocyte hypertrophy.
  findings: []
- id: PMID:16585392
  title: Role of p90 ribosomal S6 kinase-mediated prorenin-converting enzyme in ischemic and diabetic myocardium.
  findings: []
- id: PMID:19023134
  title: Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy.
  findings: []
- id: PMID:19404405
  title: Angiotensin-(1-7) and the g protein-coupled receptor MAS are key players in renal inflammation.
  findings: []
- id: PMID:19508861
  title: The heterogenous nuclear riboprotein S1-1 regulates AT1 receptor gene expression via transcriptional and posttranscriptional mechanisms.
  findings: []
- id: PMID:24206662
  title: Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia.
  findings: []
- id: PMID:26531127
  title: Age-dependent blood pressure elevation is due to increased vascular smooth muscle tone mediated by G-protein signalling.
  findings: []
- id: PMID:9466969
  title: Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes.
  findings: []
- id: PMID:9691085
  title: Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension.
  findings: []
core_functions:
- description: AGTR1A binds angiotensin II as a type 1 angiotensin receptor at the plasma membrane and activates Gq/phospholipase C/calcium signaling that underlies renin-angiotensin control of vasoconstriction, renal output, aldosterone production, and blood pressure.
  molecular_function:
    id: GO:0001596
    label: angiotensin type I receptor activity
  directly_involved_in:
  - id: GO:0038166
    label: angiotensin-activated signaling pathway
  - id: GO:0086097
    label: phospholipase C-activating angiotensin-activated signaling pathway
  - id: GO:0007204
    label: positive regulation of cytosolic calcium ion concentration
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: file:mouse/Agtr1a/Agtr1a-notes.md
    supporting_text: 'Core receptor identity: Agtr1a encodes the mouse type-1 angiotensin II receptor A, a seven-transmembrane G protein-coupled receptor whose primary molecular function is angiotensin type I receptor activity.'
  - reference_id: file:mouse/Agtr1a/Agtr1a-deep-research-falcon.md
    supporting_text: 'Agtr1a encodes a **cell-surface receptor** whose primary function is to **bind Ang II** and transduce signals through:'
proposed_new_terms: []
suggested_questions:
- question: Which mouse AGTR1A signaling outputs should be represented as direct receptor signaling annotations rather than downstream organismal blood-pressure or kidney phenotypes?
suggested_experiments:
- hypothesis: The clearest direct AGTR1A pathway annotation is Gq/PLC/calcium signaling downstream of angiotensin II.
  description: Measure Ang II-induced PLC activation, calcium mobilization, and ERK/Rho pathway activation in Agtr1a-null and rescued mouse cells, including antagonist controls and Agtr1b comparison.
  experiment_type: cell signaling rescue assay

Agtr1a

Gene Description

Existing Annotations Review

Core Functions

AGTR1A binds angiotensin II as a type 1 angiotensin receptor at the plasma membrane and activates Gq/phospholipase C/calcium signaling that underlies renin-angiotensin control of vasoconstriction, renal output, aldosterone production, and blood pressure.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

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

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

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

Research Target:

Comprehensive Research Report: Mouse Agtr1a (Angiotensin II Type-1 Receptor A; AT1aR) Functional Annotation

0) Target identity verification (critical disambiguation)

1) Key concepts and definitions (current understanding)

1.1 Receptor/ligand system

1.2 Canonical (G protein) signaling

1.3 Noncanonical signaling: β‑arrestin recruitment, internalization, and “biased agonism”

2) Subcellular and tissue/cellular localization relevant to function

2.1 Plasma membrane receptor in vascular smooth muscle: vasoconstriction and mechanosensing

2.2 Vascular endothelium in kidney and brain microvessels

2.3 Renal tubule epithelium: proximal tubule and distal nephron

2.4 CNS circuits (energy balance and sympathetic regulation)

3) Pathways and mechanistic roles (functional annotation)

3.1 Primary molecular function

3.2 Vascular function: tone, remodeling, and aneurysm biology

3.3 Renal tubular function: membrane potential and sodium handling

3.4 Endothelial counter-regulation of vasoconstriction

4) Recent developments and latest research (prioritizing 2023–2024)

4.1 Cell-type–specific genetics as a major methodological advance

4.2 β‑arrestin signaling: from receptor biology to therapeutic stratification

4.3 Direct in vivo endothelial signaling by Ang II

5) Current applications and real-world implementations

5.1 Pharmacology: ARBs as standard AT1R/AT1aR pathway inhibitors

5.2 Experimental therapeutics: β‑arrestin‑biased ligands (TRV027)

5.3 Genetic models as routine “implementations” for functional annotation

6) Quantitative statistics and data points from recent studies

6.1 Endothelial microvessel signaling (2024)

6.2 Aortic aneurysm/dissection outcomes and pharmacologic prevention (2023)

6.3 Blood pressure phenotype in cell-specific genetic models (2024 review summary)

6.4 Kidney-tubule-specific knockout validation and BP phenotype (2024; figure-based evidence)

7) Expert opinions and authoritative synthesis (2024)

8) Summary functional annotation statement (for databases/curation)

Evidence map (compact)

Citations

Notes

Agtr1a curation notes

Evidence synthesis

📄 View Raw YAML