DLL1 (Delta-like 1) is a single-pass type I transmembrane Notch ligand of the Delta/Serrate/LAG-2 (DSL) family. Its extracellular region (MNNL/N-terminal domain, DSL domain and eight EGF-like repeats) binds the EGF repeats of NOTCH1, NOTCH2 and NOTCH3 in a calcium-dependent manner. When presented on the surface of a neighbouring cell (trans), ubiquitination of the DLL1 intracellular domain by the E3 ligase MIB1 and epsin-dependent endocytosis generate a pulling force that exposes the Notch S2 site for ADAM10 cleavage, leading to gamma-secretase release of the Notch intracellular domain. DLL1 expressed in the same cell as Notch (cis) instead dampens signaling (cis-inhibition). Its C-terminal PDZ-binding motif (ATEV) binds MAGI and other PDZ scaffold proteins at adherens junctions. DLL1-Notch signaling mediates lateral inhibition and binary fate decisions in many tissues, including somite segmentation, neurogenesis, myogenesis, lymphocyte (T-cell and marginal-zone B-cell) development, pancreas, intestine, inner ear, kidney and arterial endothelium. Heterozygous loss-of-function variants cause a neurodevelopmental disorder (NEDBAS).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001709 cell fate determination | NAS PMID:11581320 Differential effects of Notch ligands Delta-1 and Jagged-1 i... | KEEP AS NON CORE | Summary: Cell fate determination in lymphoid progenitors (T vs B). Reason: Delta-1 directs human hematopoietic progenitors away from the B lineage and toward T/NK precursors; a well-documented fate role of DLL1-Notch signaling. Supporting Evidence: PMID:11581320 the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. |
| GO:0001756 somitogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Somite segmentation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 is a key ligand in the segmentation clock/somite boundary formation in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme file:human/DLL1/DLL1-deep-research-falcon.md DLL1 plays a central role in vertebrate somitogenesis by functioning as an oscillating Notch ligand within the segmentation clock |
| GO:0001756 somitogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Somite segmentation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 is a key ligand in the segmentation clock/somite boundary formation in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme file:human/DLL1/DLL1-deep-research-falcon.md DLL1 plays a central role in vertebrate somitogenesis by functioning as an oscillating Notch ligand within the segmentation clock |
| GO:0001947 heart looping | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Left-right asymmetry / heart looping (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Delta-Notch signaling at the node regulates Nodal expression in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme |
| GO:0001947 heart looping | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Left-right asymmetry / heart looping (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Delta-Notch signaling at the node regulates Nodal expression in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme |
| GO:0002315 marginal zone B cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Marginal zone B cell differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B-cells |
| GO:0002315 marginal zone B cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Marginal zone B cell differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B-cells |
| GO:0003323 type B pancreatic cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Pancreatic beta-cell development / proximodistal patterning (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium. |
| GO:0003323 type B pancreatic cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Pancreatic beta-cell development / proximodistal patterning (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium. |
| GO:0005112 Notch binding | IBA GO_REF:0000033 | ACCEPT | Summary: DLL1 is a canonical DSL-family Notch ligand; the PAINT node places Notch binding at the ancestral Delta/Serrate clade. Reason: Direct binding of DLL1 to NOTCH1/2/3 extracellular domains is experimentally established (cell-binding and solid-phase assays, affinity measurements). The IBA correctly captures the core function inherited across metazoan Delta/Serrate ligands. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005112 Notch binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic Notch binding annotation consistent with experimental data. Reason: Notch binding is the core molecular function of DLL1, directly shown for NOTCH1, NOTCH2 and NOTCH3. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner |
| GO:0005112 Notch binding | IPI PMID:10079256 Human ligands of the Notch receptor. | ACCEPT | Summary: Interaction of DLL1 with NOTCH2 reported in human ligand/receptor studies. Reason: Consistent with the well-established DLL1-Notch binding; soluble Delta1 activates NOTCH2, implying receptor engagement. Accepted as core Notch binding; curator full-text judgment deferred to. Supporting Evidence: PMID:11823422 Here we show that soluble Delta1 (sD1) activates Notch2 (N2), but much more weakly than full-length Delta1 (fD1). file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner |
| GO:0005112 Notch binding | IPI PMID:11006133 Physical interaction of Delta1, Jagged1, and Jagged2 with No... | ACCEPT | Summary: Solid-phase and cell-binding assays show direct Ca2+-dependent binding of Delta1 to NOTCH1 and NOTCH3 ectodomains. Reason: Primary experimental evidence for the core Notch-binding activity of DLL1. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. PMID:11006133 All interactions between the DSL proteins and soluble Notch proteins were dependent on Ca(2+). |
| GO:0005112 Notch binding | IPI PMID:11823422 Integrity of intracellular domain of Notch ligand is indispe... | ACCEPT | Summary: Interaction of DLL1 with NOTCH2 reported in human ligand/receptor studies. Reason: Consistent with the well-established DLL1-Notch binding; soluble Delta1 activates NOTCH2, implying receptor engagement. Accepted as core Notch binding; curator full-text judgment deferred to. Supporting Evidence: PMID:11823422 Here we show that soluble Delta1 (sD1) activates Notch2 (N2), but much more weakly than full-length Delta1 (fD1). file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner |
| GO:0005112 Notch binding | IPI PMID:23839946 Intrinsic selectivity of Notch 1 for Delta-like 4 over Delta... | ACCEPT | Summary: Purified recombinant DLL1 and NOTCH1 ectodomains bind directly in a calcium-dependent manner; affinity was measured. Reason: Direct biochemical evidence for DLL1-NOTCH1 binding; core function. Supporting Evidence: PMID:23839946 Plate-based and cell binding assays revealed a specific, calcium-dependent interaction between cell-surface and recombinant Notch receptors and ligand molecules. PMID:23839946 Truncation studies of the Dll1 and Dll4 ectodomains showed that the MNNL-EGF3 region was both necessary and sufficient for full activation. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based calcium ion binding from calcium-binding EGF-like domains. Reason: DLL1 carries Ca2+-binding EGF repeats, and DLL1-Notch interaction is Ca2+-dependent. Retained as a structural/non-core MF supporting ligand function (action aligned with this stated non-core judgement, and with the mouse Dll1, Drosophila Dl and sea urchin Delta reviews). Supporting Evidence: PMID:11006133 All interactions between the DSL proteins and soluble Notch proteins were dependent on Ca(2+). |
| GO:0005515 protein binding | IPI PMID:10079256 Human ligands of the Notch receptor. | REMOVE | Summary: Protein binding with rat Dll1 (P97677), i.e. DLL1 self-association. Reason: Generic protein binding is uninformative. Multimerization of Delta1 via its intracellular domain is proposed to be important for full signaling, but the relevant functional content (Notch binding/ligand activity) is captured elsewhere. Supporting Evidence: PMID:11823422 the multi merization of Delta1 mediated by D1(ICD) may be required for activation of the N2 intracellular cleavage. |
| GO:0005515 protein binding | IPI PMID:11823422 Integrity of intracellular domain of Notch ligand is indispe... | REMOVE | Summary: Protein binding with rat Dll1 (P97677), i.e. DLL1 self-association. Reason: Generic protein binding is uninformative. Multimerization of Delta1 via its intracellular domain is proposed to be important for full signaling, but the relevant functional content (Notch binding/ligand activity) is captured elsewhere. Supporting Evidence: PMID:11823422 the multi merization of Delta1 mediated by D1(ICD) may be required for activation of the N2 intracellular cleavage. |
| GO:0005515 protein binding | IPI PMID:15509766 Delta proteins and MAGI proteins: an interaction of Notch li... | MODIFY | Summary: DLL1 binds MAGI PDZ domains via its C-terminal ATEV motif. Reason: Generic protein binding; the paper defines a PDZ domain-mediated interaction. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:15509766 We show that these Deltas associate with the membrane-associated scaffolding proteins MAGI1, MAGI2 and MAGI3, through a direct interaction between the C termini of the Deltas and a specific PDZ domain (PDZ4) of the MAGIs. |
| GO:0005515 protein binding | IPI PMID:24025447 Synaptojanin-2 binding protein stabilizes the Notch ligands ... | MODIFY | Summary: SYNJ2BP binds the PDZ-binding motif of DLL1 and stabilises it. Reason: Generic protein binding; the interaction is with the PDZ domain of SYNJ2BP through the DLL1 PDZ-binding motif. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:24025447 Synaptojanin-2 binding protein (SYNJ2BP, also known as ARIP2) interacted with the PDZ binding motif of DLL1 and DLL4, but not with the Notch ligand Jagged-1. |
| GO:0005515 protein binding | IPI PMID:29856955 Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis t... | REMOVE | Summary: Interaction with human-specific NOTCH2NL paralogs, which inhibit cis DLL1-Notch interactions. Reason: Generic protein binding is uninformative; the interaction is real (NOTCH2NL binds DLL1 and relieves cis-inhibition) but no specific MF beyond binding is established. Removal does not dispute the interaction. Supporting Evidence: PMID:29856955 At the molecular level, NOTCH2NL function by activating the Notch pathway through inhibition of cis Delta/Notch interactions. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: High-throughput PDZ/PBM affinity survey detecting the DLL1 C-terminal PDZ-binding motif binding PDZ-domain proteins. Reason: Generic protein binding is uninformative. The assay specifically measures PDZ domain binding to the DLL1 PDZ-binding motif, so PDZ domain binding is the evidence-backed MF. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region file:human/DLL1/DLL1-uniprot.txt Interacts with MAGI1, MAGI2, MAGI3 and MPDZ |
| GO:0005576 extracellular region | NAS PMID:11823422 Integrity of intracellular domain of Notch ligand is indispe... | MARK AS OVER ANNOTATED | Summary: Extracellular region annotation based on soluble Delta1 experiments. Reason: DLL1 is a transmembrane protein; the soluble form used in PMID:11823422 is an engineered ectodomain. Although ectodomain shedding occurs, full ligand activity requires the membrane-bound, intracellular-domain-containing form. Supporting Evidence: PMID:11823422 Here we show that soluble Delta1 (sD1) activates Notch2 (N2), but much more weakly than full-length Delta1 (fD1). |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: DLL1 is a type I transmembrane ligand at the plasma membrane. Reason: Plasma membrane is the site of trans-activation of Notch on adjacent cells. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | NAS PMID:10079256 Human ligands of the Notch receptor. | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2220944 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2220976 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2660819 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2691219 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2730752 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2737728 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2769007 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2769008 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2900748 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2900765 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9013284 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9911661 | ACCEPT | Summary: Plasma membrane localization of the transmembrane ligand DLL1. Reason: Consistent with DLL1 being a cell-surface single-pass membrane ligand that signals by cell contact. Supporting Evidence: PMID:11006133 Cell-binding assays showed that soluble forms of Notch1 and Notch3 proteins physically bound to the three DSL proteins on the cell surface. |
| GO:0005912 adherens junction | IEA GO_REF:0000120 | ACCEPT | Summary: Adherens junction localization of DLL1 via MAGI1 (mouse data). Reason: Recruitment to adherens junctions via MAGI1 is documented for mouse Dll1; a context-specific localization. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Distributed around adherens junction in the apical endfeet through interactions with MAGI1. |
| GO:0005912 adherens junction | ISS GO_REF:0000024 | ACCEPT | Summary: Adherens junction localization of DLL1 via MAGI1 (mouse data). Reason: Recruitment to adherens junctions via MAGI1 is documented for mouse Dll1; a context-specific localization. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Distributed around adherens junction in the apical endfeet through interactions with MAGI1. |
| GO:0007154 cell communication | IEA GO_REF:0000002 | ACCEPT | Summary: Cell communication (InterPro DSL domain). Reason: Very general but correct; DLL1 mediates juxtacrine cell-cell communication. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner |
| GO:0007219 Notch signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: DLL1 initiates canonical Notch signaling as the ligand in the signal-sending cell. Reason: Core process; supported by experimental, phylogenetic and orthology evidence. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner file:human/DLL1/DLL1-uniprot.txt these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) |
| GO:0007219 Notch signaling pathway | IDA PMID:23839946 Intrinsic selectivity of Notch 1 for Delta-like 4 over Delta... | ACCEPT | Summary: DLL1 ectodomain activates NOTCH1 in reporter assays. Reason: Direct experimental evidence of DLL1-triggered Notch signaling. Supporting Evidence: PMID:23839946 Truncation studies of the Dll1 and Dll4 ectodomains showed that the MNNL-EGF3 region was both necessary and sufficient for full activation. |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: DLL1 initiates canonical Notch signaling as the ligand in the signal-sending cell. Reason: Core process; supported by experimental, phylogenetic and orthology evidence. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner file:human/DLL1/DLL1-uniprot.txt these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) |
| GO:0007219 Notch signaling pathway | IMP PMID:19682396 Notch signaling is required for maintaining stem-cell featur... | ACCEPT | Summary: Notch signaling in hESC-derived neuroepithelial spheres expressing DLL1. Reason: The study primarily inhibited gamma-secretase rather than DLL1 specifically, but the process annotation to DLL1 is biologically correct; deferred to curator. Supporting Evidence: PMID:19682396 Notch signaling pathway proteins such as JAG1 and DLL1 and NICD and the target gene products HES1 and HES5 were abundant in hESC-derived NESs PMID:19682396 Inhibition of the Notch signaling by a gamma-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs |
| GO:0007219 Notch signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: DLL1 initiates canonical Notch signaling as the ligand in the signal-sending cell. Reason: Core process; supported by experimental, phylogenetic and orthology evidence. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner file:human/DLL1/DLL1-uniprot.txt these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) |
| GO:0007219 Notch signaling pathway | NAS PMID:10079256 Human ligands of the Notch receptor. | ACCEPT | Summary: DLL1 described as a human Notch ligand in cloning study. Reason: Statement consistent with experimental evidence. Supporting Evidence: PMID:10079256 we have cloned and analyzed the expression of three human homologues of the Notch ligands Delta and Serrate, human Jagged1 (HJ1), human Jagged2 (HJ2), and human Delta1 (H-Delta-1) |
| GO:0007368 determination of left/right symmetry | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Left-right asymmetry / heart looping (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Delta-Notch signaling at the node regulates Nodal expression in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme |
| GO:0008217 regulation of blood pressure | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Blood pressure / energy homeostasis phenotypes from mouse Dll1 haploinsufficiency. Reason: Systemic physiological phenotypes of Dll1 heterozygous mice are indirect consequences of developmental Notch signaling defects; DLL1 does not execute these processes. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis |
| GO:0008217 regulation of blood pressure | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Blood pressure / energy homeostasis phenotypes from mouse Dll1 haploinsufficiency. Reason: Systemic physiological phenotypes of Dll1 heterozygous mice are indirect consequences of developmental Notch signaling defects; DLL1 does not execute these processes. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive and negative regulation of proliferation / cell division (mouse Dll1). Reason: Opposing, context-dependent downstream effects of Notch signaling; uninformative about DLL1 function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0008284 positive regulation of cell population proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive and negative regulation of proliferation / cell division (mouse Dll1). Reason: Opposing, context-dependent downstream effects of Notch signaling; uninformative about DLL1 function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive and negative regulation of proliferation / cell division (mouse Dll1). Reason: Opposing, context-dependent downstream effects of Notch signaling; uninformative about DLL1 function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0008285 negative regulation of cell population proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive and negative regulation of proliferation / cell division (mouse Dll1). Reason: Opposing, context-dependent downstream effects of Notch signaling; uninformative about DLL1 function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0009954 proximal/distal pattern formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Pancreatic beta-cell development / proximodistal patterning (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium. |
| GO:0009954 proximal/distal pattern formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Pancreatic beta-cell development / proximodistal patterning (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium. |
| GO:0010628 positive regulation of gene expression | IDA PMID:23839946 Intrinsic selectivity of Notch 1 for Delta-like 4 over Delta... | MARK AS OVER ANNOTATED | Summary: Positive regulation of gene expression (IDA, Notch reporter activation). Reason: The readout is Notch-responsive reporter activation, which is better captured by Notch signaling pathway; gene expression regulation is indirect. Supporting Evidence: PMID:23839946 Truncation studies of the Dll1 and Dll4 ectodomains showed that the MNNL-EGF3 region was both necessary and sufficient for full activation. |
| GO:0014002 astrocyte development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0014002 astrocyte development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0014807 regulation of somitogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Somite segmentation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 is a key ligand in the segmentation clock/somite boundary formation in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme file:human/DLL1/DLL1-deep-research-falcon.md DLL1 plays a central role in vertebrate somitogenesis by functioning as an oscillating Notch ligand within the segmentation clock |
| GO:0014807 regulation of somitogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Somite segmentation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 is a key ligand in the segmentation clock/somite boundary formation in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme file:human/DLL1/DLL1-deep-research-falcon.md DLL1 plays a central role in vertebrate somitogenesis by functioning as an oscillating Notch ligand within the segmentation clock |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Generic membrane annotation from InterPro. Reason: Correct though uninformative; plasma membrane is more specific. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Apical plasma membrane localization transferred from mouse Dll1. Reason: UniProt records apical cell membrane localization in neuroepithelial cells; plausible in polarized epithelia. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Apical cell membrane |
| GO:0016324 apical plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Apical plasma membrane localization transferred from mouse Dll1. Reason: UniProt records apical cell membrane localization in neuroepithelial cells; plausible in polarized epithelia. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Apical cell membrane |
| GO:0021510 spinal cord development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0021510 spinal cord development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0021688 cerebellar molecular layer formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0021688 cerebellar molecular layer formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0021693 cerebellar Purkinje cell layer structural organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0021693 cerebellar Purkinje cell layer structural organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0030097 hemopoiesis | NAS PMID:11581320 Differential effects of Notch ligands Delta-1 and Jagged-1 i... | KEEP AS NON CORE | Summary: Hemopoiesis (lymphopoiesis) from DLL1 co-culture study. Reason: Supported but broad; T-lineage commitment is the specific effect. Supporting Evidence: PMID:11581320 the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. |
| GO:0030154 cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cell differentiation (broad). Reason: True at a broad level (DLL1-Notch controls binary fate decisions) but very general. Non-core. Supporting Evidence: PMID:11581320 the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. |
| GO:0030154 cell differentiation | TAS PMID:11912004 The stem cell compartment in human interfollicular epidermis... | KEEP AS NON CORE | Summary: Cell differentiation (broad). Reason: True at a broad level (DLL1-Notch controls binary fate decisions) but very general. Non-core. Supporting Evidence: PMID:11581320 the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. |
| GO:0030155 regulation of cell adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Regulation of cell adhesion (mouse Dll1; satellite cells). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Directly modulates cell adhesion and basal lamina formation in satellite cells through Notch signaling. |
| GO:0030155 regulation of cell adhesion | TAS PMID:11912004 The stem cell compartment in human interfollicular epidermis... | KEEP AS NON CORE | Summary: Review of epidermal stem cell patterning proposing Delta1 roles in stem cell clustering. Reason: Traceable author statement from a review; DLL1 has adhesion-related effects in keratinocyte stem-cell clusters, retained as non-core. Supporting Evidence: PMID:11912004 beta1 integrins and Delta1 are suggested to play a role in stem cell patterning |
| GO:0030857 negative regulation of epithelial cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epithelial/epidermal differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. In intestine DLL1 restricts secretory (goblet) differentiation by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0030857 negative regulation of epithelial cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Epithelial/epidermal differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. In intestine DLL1 restricts secretory (goblet) differentiation by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:0030957 Tat protein binding | IPI PMID:15509766 Delta proteins and MAGI proteins: an interaction of Notch li... | MODIFY | Summary: IPI from a study of Delta-MAGI interaction; the partners are MAGI PDZ scaffold proteins, not HIV Tat. Reason: The paper shows the DLL1/Delta C-terminal ATEV motif binds PDZ4 of MAGI1/2/3. The appropriate MF is PDZ domain binding; 'Tat protein binding' does not describe the experiment. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:15509766 We show that these Deltas associate with the membrane-associated scaffolding proteins MAGI1, MAGI2 and MAGI3, through a direct interaction between the C termini of the Deltas and a specific PDZ domain (PDZ4) of the MAGIs. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasmic vesicle localization (mouse), consistent with ligand endocytosis and recycling. Reason: DLL1 is endocytosed after MIB1 ubiquitination; vesicular pools are expected. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation |
| GO:0032693 negative regulation of interleukin-10 production | IMP PMID:23086448 The CD46-Jagged1 interaction is critical for human TH1 immun... | KEEP AS NON CORE | Summary: Addition of soluble DLL1 reduced switching of CD4+ T cells from IFN-gamma to IL-10 production. Reason: Context-specific immunological effect; soluble ligand added exogenously. Retained as non-core. Supporting Evidence: PMID:23086448 Consistent with this hypothesis, the addition of soluble CD46, DLL1, or Jagged1 also showed a marked reduction in CD3+CD46+IL-2-mediated switching of IFN-Ξ³ to IL-10 in purified CD4+ T cells |
| GO:0034351 negative regulation of glial cell apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0034351 negative regulation of glial cell apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cerebellar Bergmann glia development and layer formation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. |
| GO:0035265 organ growth | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Organ growth / regulation of growth (mouse Dll1). Reason: Broad phenotype-level terms; DLL1 affects growth indirectly via progenitor maintenance. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0035265 organ growth | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Organ growth / regulation of growth (mouse Dll1). Reason: Broad phenotype-level terms; DLL1 affects growth indirectly via progenitor maintenance. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0040008 regulation of growth | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Organ growth / regulation of growth (mouse Dll1). Reason: Broad phenotype-level terms; DLL1 affects growth indirectly via progenitor maintenance. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0040008 regulation of growth | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Organ growth / regulation of growth (mouse Dll1). Reason: Broad phenotype-level terms; DLL1 affects growth indirectly via progenitor maintenance. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0045121 membrane raft | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Membrane raft localization transferred from mouse. Reason: Reported for mouse Dll1; peripheral to function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Membrane raft |
| GO:0045121 membrane raft | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Membrane raft localization transferred from mouse. Reason: Reported for mouse Dll1; peripheral to function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Membrane raft |
| GO:0045596 negative regulation of cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of cell differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0045605 negative regulation of epidermal cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epithelial/epidermal differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. In intestine DLL1 restricts secretory (goblet) differentiation by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0045605 negative regulation of epidermal cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Epithelial/epidermal differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. In intestine DLL1 restricts secretory (goblet) differentiation by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0045662 negative regulation of myoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0045662 negative regulation of myoblast differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0045665 negative regulation of neuron differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0045746 negative regulation of Notch signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Negative regulation of Notch signaling (IBA), reflecting cis-inhibition by Delta ligands. Reason: Delta/Serrate ligands co-expressed with Notch in the same cell inhibit signaling in cis; NOTCH2NL relieves DLL1-mediated cis-inhibition. The PAINT node placement is plausible; retained as non-core. Supporting Evidence: PMID:29856955 At the molecular level, NOTCH2NL function by activating the Notch pathway through inhibition of cis Delta/Notch interactions. file:human/DLL1/DLL1-uniprot.txt through inhibition of cis DLL1-NOTCH2 interactions |
| GO:0045747 positive regulation of Notch signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of Notch signaling (ISS from mouse/rat). Reason: DLL1 activates Notch in trans; as the ligand it is part of the pathway (GO:0007219) rather than a regulator of it, so this regulation term is somewhat redundant but not wrong (e.g., MIB1-ubiquitinated DLL1 enhances signaling). Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) |
| GO:0045747 positive regulation of Notch signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of Notch signaling (ISS from mouse/rat). Reason: DLL1 activates Notch in trans; as the ligand it is part of the pathway (GO:0007219) rather than a regulator of it, so this regulation term is somewhat redundant but not wrong (e.g., MIB1-ubiquitinated DLL1 enhances signaling). Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) |
| GO:0045807 positive regulation of endocytosis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Endocytosis terms (rat/mouse Dll1). Reason: DLL1 is the endocytic cargo whose MIB1-dependent clathrin-mediated internalization generates the pulling force for Notch activation. It is endocytosed rather than an effector of the endocytic machinery. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerization file:human/DLL1/DLL1-uniprot.txt Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation |
| GO:0045807 positive regulation of endocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Endocytosis terms (rat/mouse Dll1). Reason: DLL1 is the endocytic cargo whose MIB1-dependent clathrin-mediated internalization generates the pulling force for Notch activation. It is endocytosed rather than an effector of the endocytic machinery. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerization file:human/DLL1/DLL1-uniprot.txt Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of RNA polymerase II transcription (mouse Dll1). Reason: DLL1 is a cell-surface ligand; target-gene transcription is executed by NICD-RBPJ-MAML in the receiving cell. This term is an indirect downstream consequence. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of RNA polymerase II transcription (mouse Dll1). Reason: DLL1 is a cell-surface ligand; target-gene transcription is executed by NICD-RBPJ-MAML in the receiving cell. This term is an indirect downstream consequence. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0046331 lateral inhibition | IEA GO_REF:0000107 | ACCEPT | Summary: Lateral inhibition, the classical Delta-Notch patterning mechanism (mouse data). Reason: DLL1 is the prototypical lateral-inhibition ligand in neurogenesis and intestinal secretory fate; a core developmental process in which DLL1 is the signal. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0046331 lateral inhibition | ISS GO_REF:0000024 | ACCEPT | Summary: Lateral inhibition, the classical Delta-Notch patterning mechanism (mouse data). Reason: DLL1 is the prototypical lateral-inhibition ligand in neurogenesis and intestinal secretory fate; a core developmental process in which DLL1 is the signal. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0048018 receptor ligand activity | IDA PMID:23839946 Intrinsic selectivity of Notch 1 for Delta-like 4 over Delta... | ACCEPT | Summary: DLL1 ectodomain (MNNL-EGF3) is sufficient to activate NOTCH1 in reporter assays, i.e. DLL1 acts as a receptor ligand. Reason: Receptor ligand activity is the appropriate general MF for a signaling ligand that binds and activates a receptor. Core, together with the more specific Notch binding. Supporting Evidence: PMID:23839946 Truncation studies of the Dll1 and Dll4 ectodomains showed that the MNNL-EGF3 region was both necessary and sufficient for full activation. |
| GO:0048018 receptor ligand activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-predicted receptor ligand activity; consistent with DLL1 being a Notch ligand. Reason: Consistent with experimental data showing DLL1 activates Notch receptors. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner |
| GO:0048630 skeletal muscle tissue growth | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0048630 skeletal muscle tissue growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0048631 regulation of skeletal muscle tissue growth | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0048631 regulation of skeletal muscle tissue growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0048633 positive regulation of skeletal muscle tissue growth | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0048633 positive regulation of skeletal muscle tissue growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Myogenesis: inhibition of myoblast differentiation and muscle growth (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. file:human/DLL1/DLL1-uniprot.txt Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. |
| GO:0048665 neuron fate specification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0048665 neuron fate specification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0050767 regulation of neurogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0051302 regulation of cell division | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive and negative regulation of proliferation / cell division (mouse Dll1). Reason: Opposing, context-dependent downstream effects of Notch signaling; uninformative about DLL1 function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0051302 regulation of cell division | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive and negative regulation of proliferation / cell division (mouse Dll1). Reason: Opposing, context-dependent downstream effects of Notch signaling; uninformative about DLL1 function. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. |
| GO:0060041 retina development in camera-type eye | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0060041 retina development in camera-type eye | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0060042 retina morphogenesis in camera-type eye | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0060042 retina morphogenesis in camera-type eye | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neurogenesis in spinal cord/retina and neuronal fate (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Dll1 prevents premature neuronal differentiation of progenitors by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. file:human/DLL1/DLL1-uniprot.txt regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner |
| GO:0060853 Notch signaling pathway involved in arterial endothelial cell fate commitment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:0060853 Notch signaling pathway involved in arterial endothelial cell fate commitment | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:0070986 left/right axis specification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Left-right asymmetry / heart looping (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Delta-Notch signaling at the node regulates Nodal expression in mouse. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme |
| GO:0072006 nephron development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nephron segment development (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Plays a role during nephron development through Notch signaling pathway. |
| GO:0072006 nephron development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Nephron segment development (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Plays a role during nephron development through Notch signaling pathway. |
| GO:0072014 proximal tubule development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nephron segment development (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Plays a role during nephron development through Notch signaling pathway. |
| GO:0072070 loop of Henle development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Nephron segment development (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Plays a role during nephron development through Notch signaling pathway. |
| GO:0072583 clathrin-dependent endocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Endocytosis terms (rat/mouse Dll1). Reason: DLL1 is the endocytic cargo whose MIB1-dependent clathrin-mediated internalization generates the pulling force for Notch activation. It is endocytosed rather than an effector of the endocytic machinery. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerization file:human/DLL1/DLL1-uniprot.txt Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation |
| GO:0097009 energy homeostasis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Blood pressure / energy homeostasis phenotypes from mouse Dll1 haploinsufficiency. Reason: Systemic physiological phenotypes of Dll1 heterozygous mice are indirect consequences of developmental Notch signaling defects; DLL1 does not execute these processes. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis |
| GO:0097009 energy homeostasis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Blood pressure / energy homeostasis phenotypes from mouse Dll1 haploinsufficiency. Reason: Systemic physiological phenotypes of Dll1 heterozygous mice are indirect consequences of developmental Notch signaling defects; DLL1 does not execute these processes. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Regulates growth, blood pressure and energy homeostasis |
| GO:0097102 endothelial tip cell fate specification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:0097102 endothelial tip cell fate specification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:0097110 scaffold protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Scaffold protein binding transferred from mouse Dll1 (MAGI1 interaction). Reason: DLL1 binds MAGI scaffold proteins through its C-terminal PDZ-binding motif, recruiting it to adherens junctions. Real but ancillary to ligand function; PDZ domain binding is more precise. Supporting Evidence: PMID:15509766 We show that these Deltas associate with the membrane-associated scaffolding proteins MAGI1, MAGI2 and MAGI3, through a direct interaction between the C termini of the Deltas and a specific PDZ domain (PDZ4) of the MAGIs. file:human/DLL1/DLL1-uniprot.txt Distributed around adherens junction in the apical endfeet through interactions with MAGI1. |
| GO:0097150 neuronal stem cell population maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neural stem cell maintenance (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Maintains quiescence of neural stem cells and plays a role as a fate determinant file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. |
| GO:0097150 neuronal stem cell population maintenance | IEP PMID:19682396 Notch signaling is required for maintaining stem-cell featur... | KEEP AS NON CORE | Summary: DLL1 expression in hESC-derived neuroepithelial spheres where Notch maintains stemness. Reason: IEP reflects expression correlation; the DLL1-specific role is inferred rather than shown, but consistent with mouse data. Non-core. Supporting Evidence: PMID:19682396 Notch signaling pathway proteins such as JAG1 and DLL1 and NICD and the target gene products HES1 and HES5 were abundant in hESC-derived NESs |
| GO:0097150 neuronal stem cell population maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Neural stem cell maintenance (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Maintains quiescence of neural stem cells and plays a role as a fate determinant file:human/DLL1/DLL1-uniprot.txt At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. |
| GO:0098773 skin epidermis development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epithelial/epidermal differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. In intestine DLL1 restricts secretory (goblet) differentiation by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:0098773 skin epidermis development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Epithelial/epidermal differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. In intestine DLL1 restricts secretory (goblet) differentiation by lateral inhibition. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. |
| GO:1900746 regulation of vascular endothelial growth factor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:1900746 regulation of vascular endothelial growth factor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:1903672 positive regulation of sprouting angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:1903672 positive regulation of sprouting angiogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Arterial endothelial fate, VEGF responsiveness and sprouting angiogenesis (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression file:human/DLL1/DLL1-uniprot.txt Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. |
| GO:2000726 negative regulation of cardiac muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of cardiac muscle cell differentiation (mouse Dll1). Reason: Developmental role of mouse Dll1 transferred by orthology (ISS/Ensembl Compara). DLL1 contributes to this process as the Notch ligand presented by the signal-sending cell; the process is a downstream, tissue-specific outcome of DLL1-Notch signaling rather than the core molecular role, so it is retained as non-core. Supporting Evidence: file:human/DLL1/DLL1-uniprot.txt Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme |
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Download this section (compressed HTML)Q: How does the relative contribution of cis-inhibition versus trans-activation by DLL1 vary across tissues, and should cis-inhibition be captured as a distinct GO process on the ligand?
Q: Is the PDZ-binding (ATEV) motif of human DLL1 required for any ligand function in human cells, or only for junctional localization?
Experiment: Compare trans-activation and cis-inhibition by DLL1 mutants lacking MIB1 ubiquitination sites (e.g. Lys-613) or the ATEV motif in co-culture Notch reporter assays with human cells.
Experiment: Measure force-dependent NOTCH1/2 activation by DLL1 using DNA tension sensors to quantify the ligand pulling-force requirement.
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