Notch1 is the canonical mouse Notch receptor, a single-pass transmembrane protein that mediates juxtacrine cell-cell signaling. Ligand binding by DLL/JAG family proteins triggers ADAM and gamma-secretase cleavage, releasing the Notch intracellular domain (NICD), which enters the nucleus and forms an RBPJ/MAML transcriptional coactivator complex to activate target genes. In mouse, Notch1 has central roles in cell-fate decisions during embryogenesis and tissue homeostasis, with especially strong evidence for cardiovascular development, neurogenesis/gliogenesis, hematopoietic stem cell regulation, angiogenesis, and inhibition of myogenic differentiation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007219 Notch signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007411 axon guidance | IBA GO_REF:0000033 | REMOVE | Summary: The PANTHER IBA axon-guidance annotation appears to come from the broad PTHR45836 family, which includes both Notch receptors and canonical SLIT axon-guidance ligands. Reason: Notch1 is a Notch receptor subfamily member, whereas axon guidance is a primary SLIT-family function in the same broad PANTHER family. The PANTHER metadata and reviewed member table support treating this as a family-transfer artifact rather than a Notch1 core function. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN002911625 SUPPORTS SOURCE BUT NOT TARGET Every seed this review could identify is a SLIT-family protein: the three human SLITs by accession, and three mouse Slit records corroborated below. Four further donors - FB:FBgn0264089, WB:WBGene00004854, ZFIN:ZDB-GENE-010306-3 and ZFIN:ZDB-GENE-040310-1 - are in the WITH/FROM but resolve nowhere in the local caches, so no claim is made about them and the seed set is NOT asserted to be exclusively SLIT. That reservation is not merely formal: PTHR45836-entries.csv shows the family carries BOTH branches in exactly those lineages - worm slt-1 (G5EFX6) and fly sli (P24014) in SF4 PROTEIN SLIT, but also worm glp-1 (P13508) and zebrafish notch1a (P46530) in SF23 NEUROGENIC LOCUS NOTCH HOMOLOG PROTEIN 1 - so a fly, worm or zebrafish seed cannot be assumed SLIT from its lineage alone. The node is broad enough to span both the Notch receptors and the SLIT guidance ligands, so descent from it does not carry the SLIT function to Notch1; that argument rests on the identified seeds, which suffice. UniProtKB:O75093 · human SLIT1 SUPPORTS SOURCE BUT NOT TARGET Axon-guidance source in the WITH/FROM, not an orthologous Notch1 donor. UniProtKB:O94813 · human SLIT2 SUPPORTS SOURCE BUT NOT TARGET Axon-guidance source in the WITH/FROM, not an orthologous Notch1 donor. UniProtKB:O75094 · human SLIT3 SUPPORTS SOURCE BUT NOT TARGET Axon-guidance source in the WITH/FROM, not an orthologous Notch1 donor. MGI:MGI:1315203 · mouse Slit1 SUPPORTS SOURCE BUT NOT TARGET Corroborated, not resolved: PTHR45836-entries.csv gives Q80TR4 as Mus musculus Slit1, but this MGI id is not itself a key in that accession-keyed file and appears nowhere else in the local caches, so the MGI-to-accession step is an inference. On that reading the identified rodent donors are SLIT proteins too, sitting outside the Notch receptor branch. MGI:MGI:1315205 · mouse Slit2 SUPPORTS SOURCE BUT NOT TARGET Corroborated the same way as MGI:MGI:1315203 above: PTHR45836-entries.csv gives Q9R1B9 as Mus musculus Slit2, with the MGI-to-accession step inferred rather than looked up. MGI:MGI:1315202 · mouse Slit3 SUPPORTS SOURCE BUT NOT TARGET Corroborated the same way: PTHR45836-entries.csv gives Q9WVB4 as Mus musculus Slit3, with the MGI-to-accession step inferred rather than looked up. Mouse Notch1 signals through ligand-induced proteolysis and RBPJ, a mechanism unrelated to secreted SLIT guidance cues. Supporting Evidence: file:interpro/panther/PTHR45836/PTHR45836-metadata.yaml PTHR45836 is named Notch and Slit guidance protein and includes both Notch signaling and axonal guidance descriptions. file:interpro/panther/PTHR45836/PTHR45836-entries.csv Reviewed members include mouse Notch1 in subfamily SF12 and mouse/human Slit proteins in separate SLIT subfamilies. file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: Notch1 is expressed at the cell surface where it functions as a receptor for trans-acting ligands on neighboring cells. Reason: Cell surface localization is essential for Notch1 receptor function. The extracellular domain (N(EC)) binds ligands at the cell surface, triggering the proteolytic cascade. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043235 receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: Notch1 exists as a heterodimeric receptor complex formed by furin cleavage during maturation. The N(EC) and N(TM) fragments remain associated at the cell surface. Reason: Notch1 forms a heterodimeric complex after S1 furin cleavage in the Golgi. The extracellular and transmembrane fragments are non-covalently associated. This is well-documented in UniProt and structural studies. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001525 angiogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 plays a key role in angiogenesis by negatively regulating endothelial cell proliferation and migration. DLL4-Notch1 signaling controls tip/stalk cell selection during vascular development. Reason: While angiogenesis is a well-documented biological context for Notch1 function, it represents a tissue-specific outcome rather than the core molecular function. UniProt confirms Notch1 is involved in angiogenesis, negatively regulating endothelial cell proliferation. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001701 in utero embryonic development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in in utero embryonic development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001947 heart looping | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 is required for proper cardiac morphogenesis including heart looping during development. Reason: Heart looping is a specific developmental process. Notch1 mutations cause congenital heart defects (AOVD1), confirming cardiac development roles, but this is tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002011 morphogenesis of an epithelial sheet | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in morphogenesis of an epithelial sheet, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002064 epithelial cell development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in epithelial cell development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002437 inflammatory response to antigenic stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in inflammatory response to antigenic stimulus, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Notch1 contains multiple EGF-like domains that bind calcium ions, which are essential for proper domain folding and ligand binding. Reason: Calcium binding is a core molecular function of Notch1. The EGF-like calcium-binding domains (IPR001881) are essential for Notch1 structure and function. UniProt lists calcium ion binding in the domain annotations. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: Cytosol Reason: NICD released to cytosol before nuclear import. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: NICD forms a transcriptional activation complex with RBPJ and MAML to regulate target gene expression. Reason: The broad transcription-regulation parent is correct but too general for Notch1. The supported biology is NICD/RBPJ/MAML-dependent positive regulation of canonical Notch target transcription. Proposed replacements: positive regulation of transcription of Notch receptor target positive regulation of DNA-templated transcription Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006959 humoral immune response | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in humoral immune response, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010001 glial cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in glial cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 promotes positive regulation of epithelial to mesenchymal transition. Reason: EMT regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010720 positive regulation of cell development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of cell development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0012505 endomembrane system | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in endomembrane system, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Notch1 is a type I transmembrane protein that localizes to various cellular membranes during its lifecycle. Reason: Generic membrane is true but too broad for curation. Notch1 localization is better represented by the specific plasma membrane, Golgi membrane, endoplasmic reticulum membrane, and late endosome membrane annotations already present in this review. Proposed replacements: plasma membrane Golgi membrane endoplasmic reticulum membrane late endosome membrane Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030154 cell differentiation | IEA GO_REF:0000002 | ACCEPT | Summary: Notch1 is a master regulator of cell-fate determination and differentiation across multiple tissue contexts. Reason: Cell differentiation regulation is a core biological role of Notch1 signaling. UniProt states Notch1 affects implementation of differentiation, proliferation and apoptotic programs. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030326 embryonic limb morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in embryonic limb morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030513 positive regulation of BMP signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of bmp signaling pathway. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030858 positive regulation of epithelial cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of epithelial cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Non-activated Notch1 receptor is targeted for lysosomal degradation via the endosomal pathway. Reason: UniProt explicitly states late endosome membrane localization and notes that non-activated receptor is targeted for lysosomal degradation via the endosomal pathway. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035850 epithelial cell differentiation involved in kidney development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in epithelial cell differentiation involved in kidney development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Notch1 functions as a signaling receptor that transduces cell-cell contact signals into transcriptional responses. Reason: Signaling receptor activity is correct but too generic for Notch1, which is specifically a transmembrane receptor activated by membrane-bound ligands and regulated proteolysis. Proposed replacements: transmembrane signaling receptor activity Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of apoptotic process, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045165 cell fate commitment | IEA GO_REF:0000117 | ACCEPT | Summary: cell fate commitment is consistent with canonical mouse Notch1 receptor biology. Reason: Falcon synthesis identifies the conserved Notch1 mechanism as ER/Golgi maturation, plasma-membrane ligand reception, regulated proteolysis, NICD nuclear entry, and CSL/RBPJ-MAML transcriptional activation. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048589 developmental growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in developmental growth, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048608 reproductive structure development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in reproductive structure development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048844 artery morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in artery morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050793 regulation of developmental process | IEA GO_REF:0000002 | ACCEPT | Summary: Notch1 is a key regulator of developmental processes including cell fate determination. Reason: Developmental regulation is a well-established function of Notch1. UniProt notes roles in postimplantation development, mesoderm development, somite formation, and neurogenesis. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070986 left/right axis specification | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 annotation to left/right axis specification. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0072012 glomerulus vasculature development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in glomerulus vasculature development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0072080 nephron tubule development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in nephron tubule development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000136 regulation of cell proliferation involved in heart morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of cell proliferation involved in heart morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:17210915 Baf60c is a nuclear Notch signaling component required for t... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21102556 RITA, a novel modulator of Notch signalling, acts via nuclea... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:22258620 Pten coordinates retinal neurogenesis by regulating Notch si... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:38891776 Pin1 Downregulation Is Involved in Excess Retinoic Acid-Indu... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:8749394 Physical interaction between a novel domain of the receptor ... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 can negatively regulate certain genes through target gene specificity and crosstalk with repressive mechanisms. Reason: While Notch1 primarily activates transcription, it can also lead to repression of certain targets depending on context. This is a secondary regulatory outcome. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001554 luteolysis | IEA GO_REF:0000107 | UNDECIDED | Summary: The imported luteolysis annotation lacks gene-specific positive support in the local evidence for mouse Notch1. Reason: Luteolysis is a specialized reproductive process and the available Falcon/UniProt context does not substantiate a specific Notch1 role beyond the imported electronic annotation. Leave undecided pending direct reproductive-context evidence. |
| GO:0001669 acrosomal vesicle | IEA GO_REF:0000107 | REMOVE | Summary: The imported acrosomal vesicle annotation lacks direct mouse Notch1 localization support in the local evidence. Reason: Notch1 has well-supported membrane, endosomal, and nuclear NICD localizations, but no local evidence links mouse Notch1 to acrosomal vesicle localization or sperm acrosome biology. The imported automated localization should be removed rather than retained as undecided. |
| GO:0001837 epithelial to mesenchymal transition | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 promotes epithelial to mesenchymal transition. Reason: EMT regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002052 positive regulation of neuroblast proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 promotes neural progenitor/stem cell proliferation and maintains the undifferentiated state. Reason: Notch1 maintains neural stem cells and regulates neurogenesis, but this is a tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002193 MAML1-RBP-Jkappa- ICN1 complex | IEA GO_REF:0000107 | ACCEPT | Summary: MAML1-RBP-Jkappa-ICN1 complex Reason: Core transcription activation complex. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003151 outflow tract morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 annotation to outflow tract morphogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003180 aortic valve morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is essential for aortic valve development. Notch1 mutations cause aortic valve disease (AOVD1). Reason: Strongly supported by mouse genetics - Notch1 mutations cause bicuspid aortic valve and calcific aortic valve disease (OMIM:109730). This is a key developmental phenotype but tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003184 pulmonary valve morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates pulmonary valve development. Mouse Notch1 mutations cause pulmonary valve abnormalities. Reason: Cardiac valve development - tissue-specific developmental function supported by mouse genetics. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003192 mitral valve formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates mitral valve formation. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003264 regulation of cardioblast proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates cardioblast proliferation during heart development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003713 transcription coactivator activity | IEA GO_REF:0000107 | ACCEPT | Summary: NICD functions as a transcriptional coactivator by converting RBPJ from a repressor to an activator. Reason: Transcription coactivator activity is a core molecular function of NICD. It recruits MAML and displaces corepressors from RBPJ. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Notch1 is a transmembrane receptor that transduces signals from cell-cell contact to transcriptional responses. Reason: This is the core molecular function of Notch1. It is a type I transmembrane receptor that signals via proteolytic processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007221 positive regulation of transcription of Notch receptor target | IEA GO_REF:0000120 | ACCEPT | Summary: Positive regulation of transcription of Notch receptor target Reason: Core downstream function of NICD. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 annotation to spermatogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007507 heart development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates heart development. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of gene expression. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of gene expression. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of cardiac muscle cell apoptotic process. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010812 negative regulation of cell-substrate adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell-substrate adhesion. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0021515 cell differentiation in spinal cord | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in cell differentiation in spinal cord. Reason: Neural development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031100 animal organ regeneration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 annotation to animal organ regeneration. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in response to lipopolysaccharide. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032966 negative regulation of collagen biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of collagen biosynthetic process. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035148 tube formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 annotation to tube formation. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates cellular response to vascular endothelial growth factor stimulus. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042127 regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of cell population proliferation. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042246 tissue regeneration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 annotation to tissue regeneration. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Notch1 can form homodimers through its heterodimerization domain. Mutations in this domain cause T-ALL. Reason: Notch1 homodimerization is documented and has functional significance. The study shows leukemia-associated mutations fall into distinct mechanistic classes affecting the HD domain. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043235 receptor complex | IEA GO_REF:0000107 | ACCEPT | Summary: Notch1 exists as a heterodimeric receptor complex formed by furin cleavage during maturation. The N(EC) and N(TM) fragments remain associated at the cell surface. Reason: Notch1 forms a heterodimeric complex after S1 furin cleavage in the Golgi. The extracellular and transmembrane fragments are non-covalently associated. This is well-documented in UniProt and structural studies. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045603 positive regulation of endothelial cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates positive regulation of endothelial cell differentiation. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045662 negative regulation of myoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of myoblast differentiation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045665 negative regulation of neuron differentiation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of neuron differentiation via Notch-mediated lateral inhibition, a canonical function in the neuron-glia binary fate decision. Reason: Notch1-mediated effects on neuron differentiation are well-supported developmental outputs, but they are tissue-context consequences of the core juxtacrine receptor/NICD transcription mechanism rather than the core function itself. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045687 positive regulation of glial cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 promotes glial cell differentiation via lateral inhibition, instructing multipotent progenitors toward glial fate. Reason: Glial differentiation is a supported neural-developmental output of Notch1 signaling, but it is a context-specific consequence rather than the core receptor/NICD transcription mechanism. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: NICD positively regulates transcription by forming a coactivator complex with RBPJ and MAML that displaces corepressors. Reason: Notch1 NICD functions as a transcriptional activator. The NICD-RBPJ-MAML complex recruits coactivators like p300 to activate target gene transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046579 positive regulation of Ras protein signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 has been reported to crosstalk with Ras/MAPK signaling in certain cellular contexts. Reason: This represents crosstalk with other signaling pathways rather than the core Notch1 function. The canonical Notch pathway does not involve direct Ras activation, though downstream effects can influence Ras signaling. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048708 astrocyte differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 promotes astrocyte differentiation as part of gliogenesis, with Sox9 acting as critical downstream mediator. Reason: Astrocyte differentiation is a supported downstream neural-lineage outcome, but it is not the general core molecular or cellular function of Notch1. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048709 oligodendrocyte differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates oligodendrocyte differentiation (inhibitory role - promotes astrocyte over oligodendrocyte fate). Reason: Oligodendrocyte differentiation is a neural-lineage output of Notch1 signaling and should be retained as non-core rather than as the defining receptor/NICD function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051152 positive regulation of smooth muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 promotes vascular smooth muscle cell differentiation and is required for arterial smooth muscle development. Reason: Smooth muscle differentiation is a tissue-specific developmental outcome of Notch1 signaling rather than a core function. It represents one of many differentiation contexts where Notch1 plays a role. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060354 negative regulation of cell adhesion molecule production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell adhesion molecule production. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060412 ventricular septum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 annotation to ventricular septum morphogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0062043 positive regulation of cardiac epithelial to mesenchymal transition | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates positive regulation of cardiac epithelial to mesenchymal transition. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 can promote ERK1/2 signaling in certain cellular contexts, representing pathway crosstalk. Reason: ERK cascade regulation is not part of canonical Notch signaling but may occur through indirect mechanisms or crosstalk in specific contexts. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071228 cellular response to tumor cell | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 has been implicated in tumor microenvironment responses. Reason: This is a specialized context-dependent role of Notch1 in cancer biology rather than a core function of the protein. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071372 cellular response to follicle-stimulating hormone stimulus | IEA GO_REF:0000107 | UNDECIDED | Summary: The imported cellular response to follicle-stimulating hormone stimulus annotation lacks gene-specific positive support in the local evidence for mouse Notch1. Reason: The available Falcon/UniProt context does not substantiate a specific Notch1 response to FSH. Leave undecided pending direct reproductive-endocrine evidence. |
| GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of cell migration involved in sprouting angiogenesis. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0097150 neuronal stem cell population maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in neuronal stem cell population maintenance. Reason: Neural development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell-cell adhesion mediated by cadherin. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000737 negative regulation of stem cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of stem cell differentiation. Reason: Stem cell regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000811 negative regulation of anoikis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of anoikis. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2001027 negative regulation of endothelial cell chemotaxis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of endothelial cell chemotaxis. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 can negatively regulate certain genes through target gene specificity and crosstalk with repressive mechanisms. Reason: While Notch1 primarily activates transcription, it can also lead to repression of certain targets depending on context. This is a secondary regulatory outcome. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001837 epithelial to mesenchymal transition | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 promotes epithelial to mesenchymal transition. Reason: EMT regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002193 MAML1-RBP-Jkappa- ICN1 complex | ISO GO_REF:0000119 | ACCEPT | Summary: MAML1-RBP-Jkappa-ICN1 complex Reason: Core transcription activation complex. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003151 outflow tract morphogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 annotation to outflow tract morphogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003180 aortic valve morphogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is essential for aortic valve development. Notch1 mutations cause aortic valve disease (AOVD1). Reason: Strongly supported by mouse genetics - Notch1 mutations cause bicuspid aortic valve and calcific aortic valve disease (OMIM:109730). This is a key developmental phenotype but tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003184 pulmonary valve morphogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 regulates pulmonary valve development. Mouse Notch1 mutations cause pulmonary valve abnormalities. Reason: Cardiac valve development - tissue-specific developmental function supported by mouse genetics. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003192 mitral valve formation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 regulates mitral valve formation. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003713 transcription coactivator activity | ISO GO_REF:0000119 | ACCEPT | Summary: NICD functions as a transcriptional coactivator by converting RBPJ from a repressor to an activator. Reason: Transcription coactivator activity is a core molecular function of NICD. It recruits MAML and displaces corepressors from RBPJ. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0004888 transmembrane signaling receptor activity | ISO GO_REF:0000119 | ACCEPT | Summary: Notch1 is a transmembrane receptor that transduces signals from cell-cell contact to transcriptional responses. Reason: This is the core molecular function of Notch1. It is a type I transmembrane receptor that signals via proteolytic processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007507 heart development | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 regulates heart development. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008284 positive regulation of cell population proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008285 negative regulation of cell population proliferation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010629 negative regulation of gene expression | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of gene expression. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010812 negative regulation of cell-substrate adhesion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell-substrate adhesion. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035148 tube formation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 annotation to tube formation. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 regulates cellular response to vascular endothelial growth factor stimulus. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | ACCEPT | Summary: Notch1 can form homodimers through its heterodimerization domain. Mutations in this domain cause T-ALL. Reason: Notch1 homodimerization is documented and has functional significance. The study shows leukemia-associated mutations fall into distinct mechanistic classes affecting the HD domain. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045662 negative regulation of myoblast differentiation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of myoblast differentiation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000119 | ACCEPT | Summary: NICD positively regulates transcription by forming a coactivator complex with RBPJ and MAML that displaces corepressors. Reason: Notch1 NICD functions as a transcriptional activator. The NICD-RBPJ-MAML complex recruits coactivators like p300 to activate target gene transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046579 positive regulation of Ras protein signal transduction | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 has been reported to crosstalk with Ras/MAPK signaling in certain cellular contexts. Reason: This represents crosstalk with other signaling pathways rather than the core Notch1 function. The canonical Notch pathway does not involve direct Ras activation, though downstream effects can influence Ras signaling. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0051152 positive regulation of smooth muscle cell differentiation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 promotes vascular smooth muscle cell differentiation and is required for arterial smooth muscle development. Reason: Smooth muscle differentiation is a tissue-specific developmental outcome of Notch1 signaling rather than a core function. It represents one of many differentiation contexts where Notch1 plays a role. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060354 negative regulation of cell adhesion molecule production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell adhesion molecule production. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060412 ventricular septum morphogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 annotation to ventricular septum morphogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 can promote ERK1/2 signaling in certain cellular contexts, representing pathway crosstalk. Reason: ERK cascade regulation is not part of canonical Notch signaling but may occur through indirect mechanisms or crosstalk in specific contexts. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071228 cellular response to tumor cell | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 has been implicated in tumor microenvironment responses. Reason: This is a specialized context-dependent role of Notch1 in cancer biology rather than a core function of the protein. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071372 cellular response to follicle-stimulating hormone stimulus | ISO GO_REF:0000119 | UNDECIDED | Summary: The imported cellular response to follicle-stimulating hormone stimulus annotation lacks gene-specific positive support in the local evidence for mouse Notch1. Reason: The available Falcon/UniProt context does not substantiate a specific Notch1 response to FSH. Leave undecided pending direct reproductive-endocrine evidence. |
| GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of cell migration involved in sprouting angiogenesis. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell-cell adhesion mediated by cadherin. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000737 negative regulation of stem cell differentiation | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of stem cell differentiation. Reason: Stem cell regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000811 negative regulation of anoikis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of anoikis. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2001027 negative regulation of endothelial cell chemotaxis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of endothelial cell chemotaxis. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000137 negative regulation of cell proliferation involved in heart morphogenesis | IDA PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of cell proliferation involved in heart morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000137 negative regulation of cell proliferation involved in heart morphogenesis | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of cell proliferation involved in heart morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1990433 CSL-Notch-Mastermind transcription factor complex | ISO GO_REF:0000119 | ACCEPT | Summary: CSL-Notch-Mastermind transcription factor complex is consistent with canonical mouse Notch1 receptor biology. Reason: Falcon synthesis identifies the conserved Notch1 mechanism as ER/Golgi maturation, plasma-membrane ligand reception, regulated proteolysis, NICD nuclear entry, and CSL/RBPJ-MAML transcriptional activation. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001669 acrosomal vesicle | ISO GO_REF:0000096 | REMOVE | Summary: The imported acrosomal vesicle annotation lacks direct mouse Notch1 localization support in the local evidence. Reason: Notch1 has well-supported membrane, endosomal, and nuclear NICD localizations, but no local evidence links mouse Notch1 to acrosomal vesicle localization or sperm acrosome biology. The orthology-imported localization should be removed rather than retained as undecided. |
| GO:0002052 positive regulation of neuroblast proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 promotes neural progenitor/stem cell proliferation and maintains the undifferentiated state. Reason: Notch1 maintains neural stem cells and regulates neurogenesis, but this is a tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003264 regulation of cardioblast proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 regulates cardioblast proliferation during heart development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0004888 transmembrane signaling receptor activity | ISO GO_REF:0000096 | ACCEPT | Summary: Notch1 is a transmembrane receptor that transduces signals from cell-cell contact to transcriptional responses. Reason: This is the core molecular function of Notch1. It is a type I transmembrane receptor that signals via proteolytic processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | ISO GO_REF:0000096 | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | ISO GO_REF:0000096 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | ISO GO_REF:0000096 | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007221 positive regulation of transcription of Notch receptor target | ISO GO_REF:0000096 | ACCEPT | Summary: Positive regulation of transcription of Notch receptor target Reason: Core downstream function of NICD. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007283 spermatogenesis | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 annotation to spermatogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of gene expression. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010667 negative regulation of cardiac muscle cell apoptotic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of cardiac muscle cell apoptotic process. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032966 negative regulation of collagen biosynthetic process | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of collagen biosynthetic process. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042127 regulation of cell population proliferation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of cell population proliferation. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045603 positive regulation of endothelial cell differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 regulates positive regulation of endothelial cell differentiation. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045665 negative regulation of neuron differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of neuron differentiation via Notch-mediated lateral inhibition, a canonical function in the neuron-glia binary fate decision. Reason: Notch1-mediated effects on neuron differentiation are well-supported developmental outputs, but they are tissue-context consequences of the core juxtacrine receptor/NICD transcription mechanism rather than the core function itself. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045687 positive regulation of glial cell differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 promotes glial cell differentiation via lateral inhibition, instructing multipotent progenitors toward glial fate. Reason: Glial differentiation is a supported neural-developmental output of Notch1 signaling, but it is a context-specific consequence rather than the core receptor/NICD transcription mechanism. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048708 astrocyte differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 promotes astrocyte differentiation as part of gliogenesis, with Sox9 acting as critical downstream mediator. Reason: Astrocyte differentiation is a supported downstream neural-lineage outcome, but it is not the general core molecular or cellular function of Notch1. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0062043 positive regulation of cardiac epithelial to mesenchymal transition | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Notch1 regulates positive regulation of cardiac epithelial to mesenchymal transition. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098685 Schaffer collateral - CA1 synapse | IMP PMID:21315255 Activity-induced Notch signaling in neurons requires Arc/Arg... | KEEP AS NON CORE | Summary: Notch1 annotation to Schaffer collateral - CA1 synapse. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098685 Schaffer collateral - CA1 synapse | IDA PMID:21315255 Activity-induced Notch signaling in neurons requires Arc/Arg... | KEEP AS NON CORE | Summary: Notch1 annotation to Schaffer collateral - CA1 synapse. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098685 Schaffer collateral - CA1 synapse | IMP PMID:26635527 Notch1 Regulates Hippocampal Plasticity Through Interaction ... | KEEP AS NON CORE | Summary: Notch1 annotation to Schaffer collateral - CA1 synapse. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098685 Schaffer collateral - CA1 synapse | IDA PMID:26635527 Notch1 Regulates Hippocampal Plasticity Through Interaction ... | KEEP AS NON CORE | Summary: Notch1 annotation to Schaffer collateral - CA1 synapse. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098839 postsynaptic density membrane | IEP PMID:21315255 Activity-induced Notch signaling in neurons requires Arc/Arg... | KEEP AS NON CORE | Summary: Notch1 annotation to postsynaptic density membrane. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098839 postsynaptic density membrane | IDA PMID:21315255 Activity-induced Notch signaling in neurons requires Arc/Arg... | KEEP AS NON CORE | Summary: Notch1 annotation to postsynaptic density membrane. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098839 postsynaptic density membrane | IDA PMID:26635527 Notch1 Regulates Hippocampal Plasticity Through Interaction ... | KEEP AS NON CORE | Summary: Notch1 annotation to postsynaptic density membrane. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098978 glutamatergic synapse | IMP PMID:26635527 Notch1 Regulates Hippocampal Plasticity Through Interaction ... | KEEP AS NON CORE | Summary: Notch1 annotation to glutamatergic synapse. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0098978 glutamatergic synapse | IDA PMID:26635527 Notch1 Regulates Hippocampal Plasticity Through Interaction ... | KEEP AS NON CORE | Summary: Notch1 annotation to glutamatergic synapse. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0099565 chemical synaptic transmission, postsynaptic | IMP PMID:21315255 Activity-induced Notch signaling in neurons requires Arc/Arg... | KEEP AS NON CORE | Summary: Notch1 annotation to chemical synaptic transmission, postsynaptic. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0099565 chemical synaptic transmission, postsynaptic | IDA PMID:21315255 Activity-induced Notch signaling in neurons requires Arc/Arg... | KEEP AS NON CORE | Summary: Notch1 annotation to chemical synaptic transmission, postsynaptic. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IGI PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0061344 regulation of cell adhesion involved in heart morphogenesis | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 regulates regulation of cell adhesion involved in heart morphogenesis. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070168 negative regulation of biomineral tissue development | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of biomineral tissue development. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:22110751 Inhibitory role of Notch1 in calcific aortic valve disease. | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010008 endosome membrane | TAS Reactome:R-MMU-9793875 | ACCEPT | Summary: Endosome membrane Reason: Notch1 trafficking. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010832 negative regulation of myotube differentiation | IMP PMID:18299578 Interaction with factor inhibiting HIF-1 defines an addition... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of myotube differentiation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050768 negative regulation of neurogenesis | IMP PMID:18299578 Interaction with factor inhibiting HIF-1 defines an addition... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of neurogenesis. Reason: Neural development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071456 cellular response to hypoxia | IDA PMID:18299578 Interaction with factor inhibiting HIF-1 defines an addition... | KEEP AS NON CORE | Summary: Notch1 is involved in cellular response to hypoxia. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0140537 transcription regulator activator activity | IDA PMID:18299578 Interaction with factor inhibiting HIF-1 defines an addition... | KEEP AS NON CORE | Summary: Notch1 annotation to transcription regulator activator activity. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of transcription by RNA polymerase II. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060379 cardiac muscle cell myoblast differentiation | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 regulates cardiac muscle cell myoblast differentiation. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:27719760 BLOS2 negatively regulates Notch signaling during neural and... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:18430783 Zfp64 participates in Notch signaling and regulates differen... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030163 protein catabolic process | IDA PMID:28561022 IL-17 induced NOTCH1 activation in oligodendrocyte progenito... | KEEP AS NON CORE | Summary: Notch1 annotation to protein catabolic process. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:28561022 IL-17 induced NOTCH1 activation in oligodendrocyte progenito... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006606 protein import into nucleus | IDA PMID:28561022 IL-17 induced NOTCH1 activation in oligodendrocyte progenito... | KEEP AS NON CORE | Summary: Notch1 annotation to protein import into nucleus. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010467 gene expression | IDA PMID:28561022 IL-17 induced NOTCH1 activation in oligodendrocyte progenito... | KEEP AS NON CORE | Summary: Notch1 annotation to gene expression. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0072538 T-helper 17 type immune response | IDA PMID:28561022 IL-17 induced NOTCH1 activation in oligodendrocyte progenito... | KEEP AS NON CORE | Summary: Notch1 regulates t-helper 17 type immune response. Reason: T cell/immune development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0097400 interleukin-17-mediated signaling pathway | IDA PMID:28561022 IL-17 induced NOTCH1 activation in oligodendrocyte progenito... | KEEP AS NON CORE | Summary: Notch1 annotation to interleukin-17-mediated signaling pathway. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007221 positive regulation of transcription of Notch receptor target | IGI PMID:12794108 Notch-regulated ankyrin-repeat protein inhibits Notch1 signa... | ACCEPT | Summary: Positive regulation of transcription of Notch receptor target Reason: Core downstream function of NICD. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007221 positive regulation of transcription of Notch receptor target | IGI PMID:23160044 BCL6 controls neurogenesis through Sirt1-dependent epigeneti... | ACCEPT | Summary: Positive regulation of transcription of Notch receptor target Reason: Core downstream function of NICD. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003713 transcription coactivator activity | IDA PMID:17658278 Notch directly regulates Gata3 expression during T helper 2 ... | ACCEPT | Summary: NICD functions as a transcriptional coactivator by converting RBPJ from a repressor to an activator. Reason: Transcription coactivator activity is a core molecular function of NICD. It recruits MAML and displaces corepressors from RBPJ. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003713 transcription coactivator activity | IDA PMID:9111338 RBP-L, a transcription factor related to RBP-Jkappa. | ACCEPT | Summary: NICD functions as a transcriptional coactivator by converting RBPJ from a repressor to an activator. Reason: Transcription coactivator activity is a core molecular function of NICD. It recruits MAML and displaces corepressors from RBPJ. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003713 transcription coactivator activity | IDA PMID:17336907 Notch signaling is essential for ventricular chamber develop... | ACCEPT | Summary: NICD functions as a transcriptional coactivator by converting RBPJ from a repressor to an activator. Reason: Transcription coactivator activity is a core molecular function of NICD. It recruits MAML and displaces corepressors from RBPJ. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:24667410 Notch4 reveals a novel mechanism regulating Notch signal tra... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070168 negative regulation of biomineral tissue development | IDA PMID:23583836 Endothelial nitric oxide signaling regulates Notch1 in aorti... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of biomineral tissue development. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17336907 Notch signaling is essential for ventricular chamber develop... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0120163 negative regulation of cold-induced thermogenesis | IMP PMID:25038826 Inhibition of Notch signaling promotes browning of white adi... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cold-induced thermogenesis. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003180 aortic valve morphogenesis | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 is essential for aortic valve development. Notch1 mutations cause aortic valve disease (AOVD1). Reason: Strongly supported by mouse genetics - Notch1 mutations cause bicuspid aortic valve and calcific aortic valve disease (OMIM:109730). This is a key developmental phenotype but tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003182 coronary sinus valve morphogenesis | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 regulates coronary sinus valve development. Reason: Highly specialized cardiac structure - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003184 pulmonary valve morphogenesis | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 regulates pulmonary valve development. Mouse Notch1 mutations cause pulmonary valve abnormalities. Reason: Cardiac valve development - tissue-specific developmental function supported by mouse genetics. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003332 negative regulation of extracellular matrix constituent secretion | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 negatively regulates ECM secretion in certain contexts. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IDA PMID:26491108 Notch-Tnf signalling is required for development and homeost... | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010614 negative regulation of cardiac muscle hypertrophy | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of cardiac muscle hypertrophy. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060412 ventricular septum morphogenesis | IMP PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 annotation to ventricular septum morphogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902339 positive regulation of apoptotic process involved in morphogenesis | IDA PMID:26491108 Notch-Tnf signalling is required for development and homeost... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of apoptotic process involved in morphogenesis. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003180 aortic valve morphogenesis | IGI PMID:27107132 Endothelial Notch1 Is Required for Proper Development of the... | KEEP AS NON CORE | Summary: Notch1 is essential for aortic valve development. Notch1 mutations cause aortic valve disease (AOVD1). Reason: Strongly supported by mouse genetics - Notch1 mutations cause bicuspid aortic valve and calcific aortic valve disease (OMIM:109730). This is a key developmental phenotype but tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003184 pulmonary valve morphogenesis | IGI PMID:27107132 Endothelial Notch1 Is Required for Proper Development of the... | KEEP AS NON CORE | Summary: Notch1 regulates pulmonary valve development. Mouse Notch1 mutations cause pulmonary valve abnormalities. Reason: Cardiac valve development - tissue-specific developmental function supported by mouse genetics. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003203 endocardial cushion morphogenesis | IGI PMID:27107132 Endothelial Notch1 Is Required for Proper Development of the... | KEEP AS NON CORE | Summary: Notch1 is required for endocardial cushion development which gives rise to heart valves. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048873 homeostasis of number of cells within a tissue | IGI PMID:27107132 Endothelial Notch1 Is Required for Proper Development of the... | KEEP AS NON CORE | Summary: Notch1 annotation to homeostasis of number of cells within a tissue. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060412 ventricular septum morphogenesis | IGI PMID:27107132 Endothelial Notch1 Is Required for Proper Development of the... | KEEP AS NON CORE | Summary: Notch1 annotation to ventricular septum morphogenesis. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003180 aortic valve morphogenesis | IGI PMID:23583836 Endothelial nitric oxide signaling regulates Notch1 in aorti... | KEEP AS NON CORE | Summary: Notch1 is essential for aortic valve development. Notch1 mutations cause aortic valve disease (AOVD1). Reason: Strongly supported by mouse genetics - Notch1 mutations cause bicuspid aortic valve and calcific aortic valve disease (OMIM:109730). This is a key developmental phenotype but tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:23583836 Endothelial nitric oxide signaling regulates Notch1 in aorti... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010628 positive regulation of gene expression | IGI PMID:23583836 Endothelial nitric oxide signaling regulates Notch1 in aorti... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of gene expression. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:28089369 Deciphering the Fringe-Mediated Notch Code: Identification o... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:28498977 Consequences of MEGF10 deficiency on myoblast function and N... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048845 venous blood vessel morphogenesis | IMP PMID:18952909 Artery and vein size is balanced by Notch and ephrin B2/EphB... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in venous blood vessel morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1903849 positive regulation of aorta morphogenesis | IMP PMID:18952909 Artery and vein size is balanced by Notch and ephrin B2/EphB... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of aorta morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010468 regulation of gene expression | IMP PMID:11076679 Oscillating expression of c-Hey2 in the presomitic mesoderm ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of gene expression, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21191019 A protein (ORF2) encoded by the latency-related gene of bovi... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045070 positive regulation of viral genome replication | IMP PMID:21191019 A protein (ORF2) encoded by the latency-related gene of bovi... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of viral genome replication. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003197 endocardial cushion development | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in endocardial cushion development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:21985982 Delta-like 1-Lysine613 regulates notch signaling. | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:18676613 The intracellular region of Notch ligands Dll1 and Dll3 regu... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:24715457 Cadherin-based adhesions in the apical endfoot are required ... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005912 adherens junction | IDA PMID:24715457 Cadherin-based adhesions in the apical endfoot are required ... | KEEP AS NON CORE | Summary: Notch1 annotation to adherens junction. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0016324 apical plasma membrane | IDA PMID:24715457 Cadherin-based adhesions in the apical endfoot are required ... | KEEP AS NON CORE | Summary: Notch1 annotation to apical plasma membrane. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:12050162 The nephroblastoma overexpressed gene (NOV/ccn3) protein ass... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:25535395 Notch inhibition induces mitotically generated hair cells in... | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of transcription by RNA polymerase II. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:25535395 Notch inhibition induces mitotically generated hair cells in... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0042127 regulation of cell population proliferation | IGI PMID:25535395 Notch inhibition induces mitotically generated hair cells in... | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of cell population proliferation. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045607 regulation of inner ear auditory receptor cell differentiation | IMP PMID:25535395 Notch inhibition induces mitotically generated hair cells in... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of inner ear auditory receptor cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045608 negative regulation of inner ear auditory receptor cell differentiation | IMP PMID:25535395 Notch inhibition induces mitotically generated hair cells in... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of inner ear auditory receptor cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:25535395 Notch inhibition induces mitotically generated hair cells in... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of canonical Wnt signaling pathway, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005112 Notch binding | IPI PMID:24667410 Notch4 reveals a novel mechanism regulating Notch signal tra... | ACCEPT | Summary: Notch1 can bind other Notch family members, potentially in cis-inhibition or heterodimer formation. Reason: Notch receptors can interact with each other. The identical protein binding annotation (GO:0042802) already captures homodimerization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005783 endoplasmic reticulum | IDA PMID:24667410 Notch4 reveals a novel mechanism regulating Notch signal tra... | ACCEPT | Summary: Endoplasmic reticulum Reason: Notch1 synthesis and maturation. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IDA PMID:24667410 Notch4 reveals a novel mechanism regulating Notch signal tra... | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008593 regulation of Notch signaling pathway | IGI PMID:24667410 Notch4 reveals a novel mechanism regulating Notch signal tra... | ACCEPT | Summary: regulation of Notch signaling pathway is consistent with canonical mouse Notch1 receptor biology. Reason: Falcon synthesis identifies the conserved Notch1 mechanism as ER/Golgi maturation, plasma-membrane ligand reception, regulated proteolysis, NICD nuclear entry, and CSL/RBPJ-MAML transcriptional activation. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031410 cytoplasmic vesicle | IDA PMID:24667410 Notch4 reveals a novel mechanism regulating Notch signal tra... | KEEP AS NON CORE | Summary: Notch1 annotation to cytoplasmic vesicle. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045747 positive regulation of Notch signaling pathway | IDA PMID:24667410 Notch4 reveals a novel mechanism regulating Notch signal tra... | ACCEPT | Summary: positive regulation of Notch signaling pathway is consistent with canonical mouse Notch1 receptor biology. Reason: Falcon synthesis identifies the conserved Notch1 mechanism as ER/Golgi maturation, plasma-membrane ligand reception, regulated proteolysis, NICD nuclear entry, and CSL/RBPJ-MAML transcriptional activation. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0071944 cell periphery | IDA PMID:23284756 Ascl1 (Mash1) knockout perturbs differentiation of nonneuron... | KEEP AS NON CORE | Summary: Notch1 annotation to cell periphery. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043235 receptor complex | ISO PMID:23382219 Structural basis for endosomal trafficking of diverse transm... | ACCEPT | Summary: Notch1 exists as a heterodimeric receptor complex formed by furin cleavage during maturation. The N(EC) and N(TM) fragments remain associated at the cell surface. Reason: Notch1 forms a heterodimeric complex after S1 furin cleavage in the Golgi. The extracellular and transmembrane fragments are non-covalently associated. This is well-documented in UniProt and structural studies. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 annotation to cilium assembly. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1902263 apoptotic process involved in embryonic digit morphogenesis | IMP PMID:16245338 Notch1 signals through Jagged2 to regulate apoptosis in the ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in apoptotic process involved in embryonic digit morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001726 ruffle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in ruffle, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005856 cytoskeleton | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in cytoskeleton, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030027 lamellipodium | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in lamellipodium, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008285 negative regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035148 tube formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 annotation to tube formation. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035924 cellular response to vascular endothelial growth factor stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 regulates cellular response to vascular endothelial growth factor stimulus. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of cell migration involved in sprouting angiogenesis. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2001027 negative regulation of endothelial cell chemotaxis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 regulates negative regulation of endothelial cell chemotaxis. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035914 skeletal muscle cell differentiation | IMP PMID:22147266 Analysis of early C2C12 myogenesis identifies stably and dif... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in skeletal muscle cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:17685488 Monitoring Notch1 activity in development: evidence for a fe... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 can negatively regulate certain genes through target gene specificity and crosstalk with repressive mechanisms. Reason: While Notch1 primarily activates transcription, it can also lead to repression of certain targets depending on context. This is a secondary regulatory outcome. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:16025100 Mutations in NOTCH1 cause aortic valve disease. | KEEP AS NON CORE | Summary: Notch1 can negatively regulate certain genes through target gene specificity and crosstalk with repressive mechanisms. Reason: While Notch1 primarily activates transcription, it can also lead to repression of certain targets depending on context. This is a secondary regulatory outcome. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:16025100 Mutations in NOTCH1 cause aortic valve disease. | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:17303760 Combined loss of Hey1 and HeyL causes congenital heart defec... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003180 aortic valve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Notch1 is essential for aortic valve development. Notch1 mutations cause aortic valve disease (AOVD1). Reason: Strongly supported by mouse genetics - Notch1 mutations cause bicuspid aortic valve and calcific aortic valve disease (OMIM:109730). This is a key developmental phenotype but tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003213 cardiac right atrium morphogenesis | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 regulates right atrium morphogenesis. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003241 growth involved in heart morphogenesis | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 regulates growth during cardiac morphogenesis. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0014031 mesenchymal cell development | IMP PMID:17303760 Combined loss of Hey1 and HeyL causes congenital heart defec... | KEEP AS NON CORE | Summary: Notch1 promotes mesenchymal cell development. Reason: EMT regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030279 negative regulation of ossification | IMP PMID:21493891 Diet-induced aortic valve disease in mice haploinsufficient ... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of ossification. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:19695258 Notch1 represses osteogenic pathways in aortic valve cells. | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of dna-templated transcription. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:15107403 The Notch target genes Hey1 and Hey2 are required for embryo... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0055008 cardiac muscle tissue morphogenesis | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 regulates cardiac muscle tissue morphogenesis. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060045 positive regulation of cardiac muscle cell proliferation | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 regulates positive regulation of cardiac muscle cell proliferation. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060317 cardiac epithelial to mesenchymal transition | IMP PMID:17303760 Combined loss of Hey1 and HeyL causes congenital heart defec... | KEEP AS NON CORE | Summary: Notch1 regulates cardiac epithelial to mesenchymal transition. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060411 cardiac septum morphogenesis | IMP PMID:20007915 Distinct roles for cell-autonomous Notch signaling in cardio... | KEEP AS NON CORE | Summary: Notch1 regulates cardiac septum morphogenesis. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060842 arterial endothelial cell differentiation | IMP PMID:15107403 The Notch target genes Hey1 and Hey2 are required for embryo... | KEEP AS NON CORE | Summary: Notch1 regulates arterial endothelial cell differentiation. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 can negatively regulate certain genes through target gene specificity and crosstalk with repressive mechanisms. Reason: While Notch1 primarily activates transcription, it can also lead to repression of certain targets depending on context. This is a secondary regulatory outcome. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001947 heart looping | IGI PMID:12730124 Notch signaling regulates left-right asymmetry determination... | KEEP AS NON CORE | Summary: Notch1 is required for proper cardiac morphogenesis including heart looping during development. Reason: Heart looping is a specific developmental process. Notch1 mutations cause congenital heart defects (AOVD1), confirming cardiac development roles, but this is tissue-specific. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003160 endocardium morphogenesis | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates endocardium morphogenesis during heart development. Reason: Related to cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003162 atrioventricular node development | IMP PMID:21266778 Notch signaling regulates murine atrioventricular conduction... | KEEP AS NON CORE | Summary: Notch1 is involved in development of cardiac conduction system components. Reason: Specialized cardiac developmental process. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003169 coronary vein morphogenesis | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 regulates coronary vessel development including vein morphogenesis. Reason: Cardiac/vascular development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003181 atrioventricular valve morphogenesis | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 regulates AV valve development through endocardial cushion formation. Reason: Cardiac valve development - tissue-specific developmental function supported by mouse studies. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003181 atrioventricular valve morphogenesis | IMP PMID:21266778 Notch signaling regulates murine atrioventricular conduction... | KEEP AS NON CORE | Summary: Notch1 regulates AV valve development through endocardial cushion formation. Reason: Cardiac valve development - tissue-specific developmental function supported by mouse studies. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003198 epithelial to mesenchymal transition involved in endocardial cushion formation | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 promotes EMT during endocardial cushion formation, essential for valve development. Reason: EMT in heart development is well-documented for Notch1. Tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003203 endocardial cushion morphogenesis | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 is required for endocardial cushion development which gives rise to heart valves. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003207 cardiac chamber formation | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates cardiac chamber formation during heart development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003208 cardiac ventricle morphogenesis | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 regulates ventricular development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003209 cardiac atrium morphogenesis | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates atrial development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003214 cardiac left ventricle morphogenesis | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates left ventricle morphogenesis. Relevant to hypoplastic left heart syndrome. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003273 cell migration involved in endocardial cushion formation | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates cell migration during endocardial cushion formation. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003344 pericardium morphogenesis | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 regulates pericardium development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003344 pericardium morphogenesis | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates pericardium development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003344 pericardium morphogenesis | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 regulates pericardium development. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 promotes positive regulation of epithelial to mesenchymal transition. Reason: EMT regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030334 regulation of cell migration | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of cell migration. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030335 positive regulation of cell migration | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of cell migration. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060038 cardiac muscle cell proliferation | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 regulates cardiac muscle cell proliferation. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060843 venous endothelial cell differentiation | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates venous endothelial cell differentiation. Reason: Vascular development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060948 cardiac vascular smooth muscle cell development | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 regulates cardiac vascular smooth muscle cell development. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060956 endocardial cell differentiation | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 annotation to endocardial cell differentiation. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060979 vasculogenesis involved in coronary vascular morphogenesis | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 regulates vasculogenesis involved in coronary vascular morphogenesis. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060982 coronary artery morphogenesis | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 regulates coronary artery morphogenesis. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0061384 heart trabecula morphogenesis | IMP PMID:20890042 Integration of a Notch-dependent mesenchymal gene program an... | KEEP AS NON CORE | Summary: Notch1 regulates heart trabecula morphogenesis. Reason: Cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0070986 left/right axis specification | IGI PMID:12730124 Notch signaling regulates left-right asymmetry determination... | KEEP AS NON CORE | Summary: Notch1 annotation to left/right axis specification. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1901201 regulation of extracellular matrix assembly | IMP PMID:21311046 Differential Notch signaling in the epicardium is required f... | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of extracellular matrix assembly. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:17336907 Notch signaling is essential for ventricular chamber develop... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:1901189 positive regulation of ephrin receptor signaling pathway | IC PMID:17336907 Notch signaling is essential for ventricular chamber develop... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of ephrin receptor signaling pathway, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003157 endocardium development | IMP PMID:17336907 Notch signaling is essential for ventricular chamber develop... | KEEP AS NON CORE | Summary: Notch1 is essential for endocardium development and endocardial cell differentiation. Reason: Cardiac development is a well-established Notch1 function based on mouse disease genetics (AOVD1, AOS5), but represents tissue-specific developmental role. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003222 ventricular trabecula myocardium morphogenesis | IMP PMID:17336907 Notch signaling is essential for ventricular chamber develop... | KEEP AS NON CORE | Summary: Notch1 regulates trabeculation of the ventricular myocardium. Reason: Cardiac development - tissue-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-4396387 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9667655 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9824206 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9824230 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9824231 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-9824278 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-2064853 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-2064883 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-2065560 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005654 nucleoplasm | TAS Reactome:R-NUL-4396363 | ACCEPT | Summary: Nucleoplasm Reason: NICD functions in nucleoplasm for transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005829 cytosol | TAS Reactome:R-MMU-2067638 | ACCEPT | Summary: Cytosol Reason: NICD released to cytosol before nuclear import. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005829 cytosol | TAS Reactome:R-MMU-209285 | ACCEPT | Summary: Cytosol Reason: NICD released to cytosol before nuclear import. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005829 cytosol | TAS Reactome:R-NUL-2065902 | ACCEPT | Summary: Cytosol Reason: NICD released to cytosol before nuclear import. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019899 enzyme binding | IPI PMID:17573339 Asparaginyl hydroxylation of the Notch ankyrin repeat domain... | ACCEPT | Summary: Enzyme binding Reason: Notch1 binds enzymes involved in its processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0019899 enzyme binding | IPI PMID:18299578 Interaction with factor inhibiting HIF-1 defines an addition... | ACCEPT | Summary: Enzyme binding Reason: Notch1 binds enzymes involved in its processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:19245366 MYPT1, the targeting subunit of smooth-muscle myosin phospha... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0004857 enzyme inhibitor activity | IDA PMID:17573339 Asparaginyl hydroxylation of the Notch ankyrin repeat domain... | KEEP AS NON CORE | Summary: The Notch1 ankyrin-repeat domain can inhibit factor inhibiting HIF (FIH) in vitro, but this is a context-specific biochemical interaction rather than the core Notch receptor function. Reason: PMID:17573339 reports that Notch ankyrin-repeat domains compete with HIF for FIH-dependent hydroxylation and proposes ARD proteins as natural FIH inhibitors. Retain the term as supported non-core biochemistry, distinct from canonical Notch ligand-receptor signaling and NICD transcriptional coactivation. Supporting Evidence: PMID:17573339 ARD proteins were found to efficiently compete with HIF for FIH-dependent hydroxylation file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon synthesis identifies Notch1 core function as ligand-triggered receptor cleavage and NICD/CSL/MAML transcriptional signaling; FIH inhibition is peripheral.] |
| GO:0005634 nucleus | IDA PMID:18299578 Interaction with factor inhibiting HIF-1 defines an addition... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IDA PMID:21419176 The EGF-like proteins DLK1 and DLK2 function as inhibitory n... | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043086 negative regulation of catalytic activity | IDA PMID:17573339 Asparaginyl hydroxylation of the Notch ankyrin repeat domain... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of catalytic activity. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-2053938 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-2053963 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-2066712 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-2067638 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-2071906 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-2077477 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-MMU-2077479 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-2065902 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-209162 | KEEP AS NON CORE | Summary: Notch1 annotation to extracellular region. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000139 Golgi membrane | TAS Reactome:R-MMU-2023158 | ACCEPT | Summary: Notch1 undergoes S1 cleavage by furin in the trans-Golgi network during maturation, converting the precursor into the functional heterodimer. Reason: Golgi membrane localization is part of the Notch1 biosynthetic pathway. UniProt states the precursor is proteolytically cleaved by furin-like convertase in the trans-Golgi network before reaching the plasma membrane. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000139 Golgi membrane | TAS Reactome:R-MMU-2032750 | ACCEPT | Summary: Notch1 undergoes S1 cleavage by furin in the trans-Golgi network during maturation, converting the precursor into the functional heterodimer. Reason: Golgi membrane localization is part of the Notch1 biosynthetic pathway. UniProt states the precursor is proteolytically cleaved by furin-like convertase in the trans-Golgi network before reaching the plasma membrane. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-MMU-2023179 | ACCEPT | Summary: Notch1 is synthesized and begins its maturation in the ER membrane before trafficking to the Golgi. Reason: ER membrane localization is part of the Notch1 biosynthetic pathway. UniProt notes synthesis in the endoplasmic reticulum as an inactive form. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-MMU-2032750 | ACCEPT | Summary: Notch1 is synthesized and begins its maturation in the ER membrane before trafficking to the Golgi. Reason: ER membrane localization is part of the Notch1 biosynthetic pathway. UniProt notes synthesis in the endoplasmic reticulum as an inactive form. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-MMU-9824249 | ACCEPT | Summary: Notch1 is synthesized and begins its maturation in the ER membrane before trafficking to the Golgi. Reason: ER membrane localization is part of the Notch1 biosynthetic pathway. UniProt notes synthesis in the endoplasmic reticulum as an inactive form. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-NUL-1986584 | ACCEPT | Summary: Notch1 is synthesized and begins its maturation in the ER membrane before trafficking to the Golgi. Reason: ER membrane localization is part of the Notch1 biosynthetic pathway. UniProt notes synthesis in the endoplasmic reticulum as an inactive form. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-209285 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-2063915 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-209162 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2053938 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:15574878 Fringe glycosyltransferases differentially modulate Notch1 p... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009986 cell surface | IDA PMID:15574878 Fringe glycosyltransferases differentially modulate Notch1 p... | ACCEPT | Summary: Notch1 is expressed at the cell surface where it functions as a receptor for trans-acting ligands on neighboring cells. Reason: Cell surface localization is essential for Notch1 receptor function. The extracellular domain (N(EC)) binds ligands at the cell surface, triggering the proteolytic cascade. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002437 inflammatory response to antigenic stimulus | IGI PMID:17658279 Direct regulation of Gata3 expression determines the T helpe... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in inflammatory response to antigenic stimulus, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006959 humoral immune response | IGI PMID:17658279 Direct regulation of Gata3 expression determines the T helpe... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in humoral immune response, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003219 cardiac right ventricle formation | IMP PMID:19620969 A regulatory pathway involving Notch1/beta-catenin/Isl1 dete... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in cardiac right ventricle formation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IMP PMID:19620969 A regulatory pathway involving Notch1/beta-catenin/Isl1 dete... | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:19620969 A regulatory pathway involving Notch1/beta-catenin/Isl1 dete... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of canonical Wnt signaling pathway, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:20547764 ZFP423 coordinates Notch and bone morphogenetic protein sign... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030513 positive regulation of BMP signaling pathway | IDA PMID:20547764 ZFP423 coordinates Notch and bone morphogenetic protein sign... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of bmp signaling pathway. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:20547764 ZFP423 coordinates Notch and bone morphogenetic protein sign... | ACCEPT | Summary: NICD positively regulates transcription by forming a coactivator complex with RBPJ and MAML that displaces corepressors. Reason: Notch1 NICD functions as a transcriptional activator. The NICD-RBPJ-MAML complex recruits coactivators like p300 to activate target gene transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:2000974 negative regulation of pro-B cell differentiation | IMP PMID:12032823 Overexpression of the Notch target genes Hes in vivo induces... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of pro-b cell differentiation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT | IDA PMID:15156153 Hes binding to STAT3 mediates crosstalk between Notch and JA... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of receptor signaling pathway via jak-stat. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:12032823 Overexpression of the Notch target genes Hes in vivo induces... | KEEP AS NON CORE | Summary: Notch1 can negatively regulate certain genes through target gene specificity and crosstalk with repressive mechanisms. Reason: While Notch1 primarily activates transcription, it can also lead to repression of certain targets depending on context. This is a secondary regulatory outcome. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:12666205 Hes1 but not Hes5 regulates an astrocyte versus oligodendroc... | ACCEPT | Summary: NICD positively regulates transcription by forming a coactivator complex with RBPJ and MAML that displaces corepressors. Reason: Notch1 NICD functions as a transcriptional activator. The NICD-RBPJ-MAML complex recruits coactivators like p300 to activate target gene transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048711 positive regulation of astrocyte differentiation | IDA PMID:12666205 Hes1 but not Hes5 regulates an astrocyte versus oligodendroc... | KEEP AS NON CORE | Summary: Notch1 positively regulates astrocyte differentiation via HES/HEY transcriptional targets. Reason: Positive regulation of astrocyte differentiation is a supported downstream neural-lineage output of Notch1 signaling, but it is not the general core receptor/NICD transcription function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048715 negative regulation of oligodendrocyte differentiation | IDA PMID:12666205 Hes1 but not Hes5 regulates an astrocyte versus oligodendroc... | KEEP AS NON CORE | Summary: Notch1 negatively regulates oligodendrocyte differentiation, favoring astrocyte fate. Reason: Negative regulation of oligodendrocyte differentiation is a neural-lineage output of Notch1 signaling and should be retained as non-core rather than as the defining receptor/NICD function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060253 negative regulation of glial cell proliferation | IDA PMID:12666205 Hes1 but not Hes5 regulates an astrocyte versus oligodendroc... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of glial cell proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0072017 distal tubule development | IEP PMID:15821257 Segmental expression of Notch and Hairy genes in nephrogenes... | KEEP AS NON CORE | Summary: Notch1 annotation to distal tubule development. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0072044 collecting duct development | IEP PMID:15821257 Segmental expression of Notch and Hairy genes in nephrogenes... | KEEP AS NON CORE | Summary: Notch1 annotation to collecting duct development. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0072144 glomerular mesangial cell development | IEP PMID:15821257 Segmental expression of Notch and Hairy genes in nephrogenes... | KEEP AS NON CORE | Summary: Notch1 annotation to glomerular mesangial cell development. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IMP PMID:19154718 Hey2 regulation by FGF provides a Notch-independent mechanis... | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0009912 auditory receptor cell fate commitment | IMP PMID:19154718 Hey2 regulation by FGF provides a Notch-independent mechanis... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in auditory receptor cell fate commitment, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045665 negative regulation of neuron differentiation | IGI PMID:10205173 Hes1 and Hes5 as notch effectors in mammalian neuronal diffe... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of neuron differentiation via Notch-mediated lateral inhibition, a canonical function in the neuron-glia binary fate decision. Reason: Notch1-mediated effects on neuron differentiation are well-supported developmental outputs, but they are tissue-context consequences of the core juxtacrine receptor/NICD transcription mechanism rather than the core function itself. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045955 negative regulation of calcium ion-dependent exocytosis | IMP PMID:19251639 Notch and Wnt signals cooperatively control cell proliferati... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of calcium ion-dependent exocytosis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050679 positive regulation of epithelial cell proliferation | IGI PMID:19251639 Notch and Wnt signals cooperatively control cell proliferati... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of epithelial cell proliferation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0032495 response to muramyl dipeptide | IDA PMID:21156799 Intracellular pathogen sensor NOD2 programs macrophages to t... | KEEP AS NON CORE | Summary: Notch1 is involved in response to muramyl dipeptide. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030514 negative regulation of BMP signaling pathway | IMP PMID:19695258 Notch1 represses osteogenic pathways in aortic valve cells. | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of bmp signaling pathway. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045668 negative regulation of osteoblast differentiation | IMP PMID:19695258 Notch1 represses osteogenic pathways in aortic valve cells. | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of osteoblast differentiation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002051 osteoblast fate commitment | NAS PMID:16025100 Mutations in NOTCH1 cause aortic valve disease. | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in osteoblast fate commitment, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003160 endocardium morphogenesis | IEP PMID:16025100 Mutations in NOTCH1 cause aortic valve disease. | KEEP AS NON CORE | Summary: Notch1 regulates endocardium morphogenesis during heart development. Reason: Related to cardiac development - tissue-specific developmental function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:16025100 Mutations in NOTCH1 cause aortic valve disease. | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of dna-templated transcription. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060528 secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development | IMP PMID:16360140 Notch signaling is required for normal prostatic epithelial ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060740 prostate gland epithelium morphogenesis | IMP PMID:16360140 Notch signaling is required for normal prostatic epithelial ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in prostate gland epithelium morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0060768 regulation of epithelial cell proliferation involved in prostate gland development | IMP PMID:16360140 Notch signaling is required for normal prostatic epithelial ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of epithelial cell proliferation involved in prostate gland development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001701 in utero embryonic development | IMP PMID:7789282 Notch1 is required for the coordinate segmentation of somite... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in in utero embryonic development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007368 determination of left/right symmetry | IMP PMID:7789282 Notch1 is required for the coordinate segmentation of somite... | KEEP AS NON CORE | Summary: Notch1 annotation to determination of left/right symmetry. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0014807 regulation of somitogenesis | IMP PMID:7789282 Notch1 is required for the coordinate segmentation of somite... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of somitogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0021915 neural tube development | IMP PMID:7789282 Notch1 is required for the coordinate segmentation of somite... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in neural tube development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043069 negative regulation of programmed cell death | IMP PMID:7789282 Notch1 is required for the coordinate segmentation of somite... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of programmed cell death, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:16324690 BMP7 inhibits branching morphogenesis in the prostate gland ... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:9111338 RBP-L, a transcription factor related to RBP-Jkappa. | ACCEPT | Summary: NICD positively regulates transcription by forming a coactivator complex with RBPJ and MAML that displaces corepressors. Reason: Notch1 NICD functions as a transcriptional activator. The NICD-RBPJ-MAML complex recruits coactivators like p300 to activate target gene transcription. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:10958687 Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly in... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:9315665 Isolation and functional analysis of a cDNA for human Jagged... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001889 liver development | IMP PMID:15226394 Notch signaling controls hepatoblast differentiation by alte... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in liver development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010468 regulation of gene expression | IMP PMID:9102301 Conservation of the Notch signalling pathway in mammalian ne... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of gene expression, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030182 neuron differentiation | IMP PMID:9102301 Conservation of the Notch signalling pathway in mammalian ne... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in neuron differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050767 regulation of neurogenesis | IMP PMID:9102301 Conservation of the Notch signalling pathway in mammalian ne... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of neurogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2053963 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2066712 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2067638 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2071906 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2077477 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2077479 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | TAS Reactome:R-NUL-2065902 | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:17079689 Canonical notch signaling functions as a commitment switch i... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IDA PMID:17079689 Canonical notch signaling functions as a commitment switch i... | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045618 positive regulation of keratinocyte differentiation | IGI PMID:16618808 Cross-regulation between Notch and p63 in keratinocyte commi... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of keratinocyte differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045618 positive regulation of keratinocyte differentiation | IDA PMID:17079689 Canonical notch signaling functions as a commitment switch i... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of keratinocyte differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16618808 Cross-regulation between Notch and p63 in keratinocyte commi... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IGI PMID:16618808 Cross-regulation between Notch and p63 in keratinocyte commi... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031490 chromatin DNA binding | IDA PMID:17658278 Notch directly regulates Gata3 expression during T helper 2 ... | KEEP AS NON CORE | Summary: Notch1 annotation to chromatin DNA binding. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:17658278 Notch directly regulates Gata3 expression during T helper 2 ... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0046533 negative regulation of photoreceptor cell differentiation | IMP PMID:16452096 Notch 1 inhibits photoreceptor production in the developing ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of photoreceptor cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005737 cytoplasm | IDA PMID:15965470 DNER acts as a neuron-specific Notch ligand during Bergmann ... | ACCEPT | Summary: Cytoplasm Reason: NICD transits through cytoplasm. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0010001 glial cell differentiation | IMP PMID:15965470 DNER acts as a neuron-specific Notch ligand during Bergmann ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in glial cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:16607638 Jag2-Notch1 signaling regulates oral epithelial differentiat... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007440 foregut morphogenesis | IMP PMID:16107537 Direct regulation of intestinal fate by Notch. | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in foregut morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045165 cell fate commitment | IMP PMID:16107537 Direct regulation of intestinal fate by Notch. | ACCEPT | Summary: cell fate commitment is consistent with canonical mouse Notch1 receptor biology. Reason: Falcon synthesis identifies the conserved Notch1 mechanism as ER/Golgi maturation, plasma-membrane ligand reception, regulated proteolysis, NICD nuclear entry, and CSL/RBPJ-MAML transcriptional activation. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0050678 regulation of epithelial cell proliferation | IMP PMID:16107537 Direct regulation of intestinal fate by Notch. | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in regulation of epithelial cell proliferation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0002040 sprouting angiogenesis | IMP PMID:15809373 Essential role of endothelial Notch1 in angiogenesis. | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in sprouting angiogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031069 hair follicle morphogenesis | IMP PMID:15978571 Notch1 is essential for postnatal hair follicle development ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in hair follicle morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030326 embryonic limb morphogenesis | IGI PMID:16169548 Notch1 and 2 cooperate in limb ectoderm to receive an early ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in embryonic limb morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043065 positive regulation of apoptotic process | IGI PMID:16169548 Notch1 and 2 cooperate in limb ectoderm to receive an early ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of apoptotic process, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0035116 embryonic hindlimb morphogenesis | IMP PMID:16245338 Notch1 signals through Jagged2 to regulate apoptosis in the ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in embryonic hindlimb morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16145673 Fjx1: a notch-inducible secreted ligand with specific bindin... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048754 branching morphogenesis of an epithelial tube | IMP PMID:15064243 Functional diversity of notch family genes in fetal lung dev... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in branching morphogenesis of an epithelial tube, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005634 nucleus | IDA PMID:10206645 A presenilin-1-dependent gamma-secretase-like protease media... | ACCEPT | Summary: The Notch1 intracellular domain (NICD) translocates to the nucleus following gamma-secretase cleavage to activate transcription. Reason: Nuclear localization of NICD is essential for Notch1 signaling. UniProt confirms NICD translocates to the nucleus following proteolytical processing. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007409 axonogenesis | IMP PMID:16120638 Notch signaling coordinates the patterning of striatal compa... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in axonogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030900 forebrain development | IMP PMID:16120638 Notch signaling coordinates the patterning of striatal compa... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in forebrain development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030900 forebrain development | IGI PMID:16120638 Notch signaling coordinates the patterning of striatal compa... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in forebrain development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045665 negative regulation of neuron differentiation | IMP PMID:16120638 Notch signaling coordinates the patterning of striatal compa... | KEEP AS NON CORE | Summary: Notch1 is involved in negative regulation of neuron differentiation via Notch-mediated lateral inhibition, a canonical function in the neuron-glia binary fate decision. Reason: Notch1-mediated effects on neuron differentiation are well-supported developmental outputs, but they are tissue-context consequences of the core juxtacrine receptor/NICD transcription mechanism rather than the core function itself. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048663 neuron fate commitment | IGI PMID:16120638 Notch signaling coordinates the patterning of striatal compa... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in neuron fate commitment, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:15902259 The Mesp2 transcription factor establishes segmental borders... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001708 cell fate specification | IMP PMID:15068794 High commitment of embryonic keratinocytes to terminal diffe... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in cell fate specification, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007409 axonogenesis | IDA PMID:15598981 Targeted deletion of numb and numblike in sensory neurons re... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in axonogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030154 cell differentiation | IMP PMID:12186854 Notch1 control of oligodendrocyte differentiation in the spi... | ACCEPT | Summary: Notch1 is a master regulator of cell-fate determination and differentiation across multiple tissue contexts. Reason: Cell differentiation regulation is a core biological role of Notch1 signaling. UniProt states Notch1 affects implementation of differentiation, proliferation and apoptotic programs. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030216 keratinocyte differentiation | IMP PMID:15068794 High commitment of embryonic keratinocytes to terminal diffe... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in keratinocyte differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0003682 chromatin binding | IDA PMID:15689374 RBPjkappa-dependent Notch function regulates Gata2 and is es... | ACCEPT | Summary: NICD associates with chromatin as part of the transcription activation complex with RBPJ. Reason: NICD binds to chromatin at target gene promoters as part of the RBPJ-MAML transcription complex. This is part of the core transcriptional mechanism. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0006357 regulation of transcription by RNA polymerase II | IGI PMID:15689374 RBPjkappa-dependent Notch function regulates Gata2 and is es... | KEEP AS NON CORE | Summary: Notch1 annotation to regulation of transcription by RNA polymerase II. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030324 lung development | IMP PMID:15064243 Functional diversity of notch family genes in fetal lung dev... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in lung development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045596 negative regulation of cell differentiation | IMP PMID:15064243 Functional diversity of notch family genes in fetal lung dev... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in negative regulation of cell differentiation, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008284 positive regulation of cell population proliferation | IGI PMID:15509736 Fibroblast growth factor receptor signaling promotes radial ... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of cell population proliferation. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12783854 Periodic repression by the bHLH factor Hes7 is an essential ... | KEEP AS NON CORE | Summary: Notch1 is involved in positive regulation of transcription by rna polymerase ii. Reason: Context-dependent regulatory function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048103 somatic stem cell division | IGI PMID:15509736 Fibroblast growth factor receptor signaling promotes radial ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in somatic stem cell division, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0008544 epidermis development | IGI PMID:15525534 gamma-secretase functions through Notch signaling to maintai... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in epidermis development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0031069 hair follicle morphogenesis | IMP PMID:15525534 gamma-secretase functions through Notch signaling to maintai... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in hair follicle morphogenesis, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0043065 positive regulation of apoptotic process | IDA PMID:15081359 Notch activation induces apoptosis in neural progenitor cell... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in positive regulation of apoptotic process, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0001837 epithelial to mesenchymal transition | IMP PMID:14701881 Notch promotes epithelial-mesenchymal transition during card... | KEEP AS NON CORE | Summary: Notch1 promotes epithelial to mesenchymal transition. Reason: EMT regulation - context-dependent function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007492 endoderm development | IMP PMID:14657333 Notch signaling controls multiple steps of pancreatic differ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in endoderm development, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0030154 cell differentiation | IMP PMID:14657333 Notch signaling controls multiple steps of pancreatic differ... | ACCEPT | Summary: Notch1 is a master regulator of cell-fate determination and differentiation across multiple tissue contexts. Reason: Cell differentiation regulation is a core biological role of Notch1 signaling. UniProt states Notch1 affects implementation of differentiation, proliferation and apoptotic programs. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005886 plasma membrane | IC PMID:10551863 Mouse jagged1 physically interacts with notch2 and other not... | ACCEPT | Summary: Notch1 is a type I transmembrane receptor that resides at the plasma membrane where it receives ligand signals from adjacent cells. Reason: Plasma membrane localization is essential for Notch1 receptor function. The mature Notch1 heterodimer traffics to and resides at the plasma membrane where it undergoes ligand-dependent activation. UniProt confirms cell membrane localization. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007219 Notch signaling pathway | IC PMID:10551863 Mouse jagged1 physically interacts with notch2 and other not... | ACCEPT | Summary: Notch1 is the canonical receptor for the Notch signaling pathway. Upon ligand binding (JAG1/2, DLL1/3/4), Notch1 undergoes proteolytic cleavage releasing NICD which translocates to the nucleus to activate target genes via RBPJ/MAML complex. Reason: This is the core function of Notch1. The protein is THE defining receptor of the Notch signaling pathway, as documented extensively in UniProt and literature (Shi et al. 2024, doi:10.1038/s41392-024-01828-x). Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0048103 somatic stem cell division | IDA PMID:12717450 A role for Wnt signalling in self-renewal of haematopoietic ... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in somatic stem cell division, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007368 determination of left/right symmetry | IMP PMID:12730124 Notch signaling regulates left-right asymmetry determination... | KEEP AS NON CORE | Summary: Notch1 annotation to determination of left/right symmetry. Reason: Transferred annotation - context-specific function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0005515 protein binding | IPI PMID:10551863 Mouse jagged1 physically interacts with notch2 and other not... | REMOVE | Summary: The protein binding annotation records a physical interaction but is too generic to describe Notch1 function. Reason: Per curation guidance, generic protein binding should not be retained when the functional biology is a specific Notch receptor/ligand/coactivator pathway. Notch1 interactions are better captured by receptor activity, Notch signaling, and NICD-CSL/RBPJ-MAML transcriptional complex terms. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
| GO:0007386 compartment pattern specification | IMP PMID:12001066 Segmentation defects of Notch pathway mutants and absence of... | KEEP AS NON CORE | Summary: Notch1 has evidence for involvement in compartment pattern specification, but this represents a tissue- or context-specific developmental/signaling output rather than the core receptor mechanism. Reason: The core Notch1 function is juxtacrine receptor signaling followed by NICD-mediated transcriptional regulation. This annotation is biologically plausible in mouse but is retained as non-core to avoid conflating downstream pleiotropic phenotypes with the primary molecular/cellular function. Supporting Evidence: file:mouse/Notch1/Notch1-deep-research-falcon.md [Falcon deep-research synthesis used for this annotation decision.] |
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