Neuralized (Neur) is a membrane-associated RING-type E3 ubiquitin ligase that activates the Notch ligands Delta and Serrate in signal-sending cells. Its NHR1 (neuralized homology repeat) domain docks onto an NXXN motif in the Delta intracellular domain, and its C-terminal RING domain transfers ubiquitin to lysines of the ligand intracellular domain, routing the ligand into Epsin-dependent endocytosis that is required for productive trans-activation of Notch. A basic phosphoinositide-binding motif targets Neur to the plasma membrane. Neur is expressed in neural precursors (SOPs), segregates asymmetrically into pIIb during SOP division, and is the dominant ligand E3 for lateral inhibition and SOP lineage decisions, whereas the structurally unrelated Mind bomb 1 acts in most other Notch contexts; Neur can functionally substitute for Mib1. Neur activity is antagonised by Bearded-family proteins, which compete with Delta for NHR1 binding. Neur also targets Stardust isoforms to promote Crumbs endocytosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000209 protein polyubiquitination | IDA PMID:22162135 Distinct intracellular motifs of Delta mediate its ubiquityl... | ACCEPT | Summary: Neur catalyses multi-/polyubiquitylation of the Delta intracellular domain in a cell-based assay. Reason: IDA from a direct ubiquitylation assay on the Neur substrate Delta; the product was multi- or polyubiquitylated Dl. This is the process realised by Neur's E3 activity. Note that the signalling-relevant modification may be multi-monoubiquitylation; the term is acceptable as the paper reports high-molecular-mass poly/multi-ubiquitin species. Supporting Evidence: PMID:22162135 Using a cell-based assay, we detected ubiquitylation of Dl by both Neur and Mib1. PMID:22162135 This shows that these E3 ligases catalyze preferentially the multi- or polyubiquitylation of Dl. |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-DME-209226 | ACCEPT | Summary: Reactome places Neur (with Mib1) as the E3 that ubiquitinates DL/SER. Reason: Correct but less specific parent of ubiquitin protein ligase activity (GO:0061630), which is directly supported. Retained; GO:0061630 is the preferred core term. Supporting Evidence: PMID:11740940 In this report, we present genetic and biochemical evidence that Neur is a RING-type, E3 ubiquitin ligase. PMID:22162135 Using a cell-based assay, we detected ubiquitylation of Dl by both Neur and Mib1. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | REMOVE | Summary: Neur binds Bearded family proteins (Tom and other BFMs), which inhibit Neur-mediated Delta endocytosis. Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:16459303 In this study, we identify proteins of the Bearded (Brd) family as interactors of Neur. PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005515 protein binding | IPI PMID:19580805 Both inhibition and activation of Notch signaling rely on a ... | REMOVE | Summary: Neur binds the NXXN motif of Bearded family proteins (and of Delta). Reason: GO:0005515 protein binding is uninformative. The IPI rows from this paper record binding of Neur to Bearded-family proteins (BFMs), which are Neur inhibitors that compete with Delta for the Neur NHR1 substrate-docking surface. The interaction is real and biologically important, but no more informative molecular function of Neur is captured by binding its inhibitor; removal does not dispute the interaction. Supporting Evidence: PMID:19580805 we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | REMOVE | Summary: Nuclear localization from UniProt subcellular location, which is itself flagged by curator inference (ECO:0000305). Reason: All experimental localization data place Neur at the plasma membrane (via its phosphoinositide-binding motif), apical cortex, cytoplasm and endosomes, where it ubiquitinates DSL ligands. No experimental support for nuclear localization is available; the early proposal of a nuclear/DNA-binding role predates the characterization of the NHR and RING domains. This electronic mapping should not be propagated. Supporting Evidence: PMID:10970873 We show that Neu protein is localized primarily at the plasma membrane. PMID:18061562 We show that interactions between phosphoinositides and Neuralized contribute to the membrane localization of Neuralized in the absence of Delta, and that the phosphoinositide-binding motif is required for Neuralized to endocytose Delta downstream of Delta ubiquitination. PMID:28400441 Neuralized (Neur) is a conserved membrane-associated E3 ubiquitin ligase |
| GO:0005737 cytoplasm | IDA PMID:12852858 Unequal segregation of Neuralized biases Notch activation du... | ACCEPT | Summary: Neur is detected in the cytoplasm/cell cortex, including asymmetric cortical crescents in dividing SOPs. Reason: Consistent with its role as a membrane-associated cytoplasmic-face E3 ligase. Supporting Evidence: PMID:12852858 We report that the E3 ubiquitin ligase Neuralized localizes asymmetrically in the dividing pI cell and unequally segregates into the pIIb cell, like the Notch inhibitor Numb. PMID:28400441 Neuralized (Neur) is a conserved membrane-associated E3 ubiquitin ligase |
| GO:0005737 cytoplasm | IDA PMID:18061562 Neuralized contains a phosphoinositide-binding motif require... | ACCEPT | Summary: Neur is detected in the cytoplasm/cell cortex, including asymmetric cortical crescents in dividing SOPs. Reason: Consistent with its role as a membrane-associated cytoplasmic-face E3 ligase. Supporting Evidence: PMID:12852858 We report that the E3 ubiquitin ligase Neuralized localizes asymmetrically in the dividing pI cell and unequally segregates into the pIIb cell, like the Notch inhibitor Numb. PMID:28400441 Neuralized (Neur) is a conserved membrane-associated E3 ubiquitin ligase |
| GO:0005737 cytoplasm | IDA PMID:28400441 Neuralized regulates Crumbs endocytosis and epithelium morph... | ACCEPT | Summary: Neur is detected in the cytoplasm/cell cortex, including asymmetric cortical crescents in dividing SOPs. Reason: Consistent with its role as a membrane-associated cytoplasmic-face E3 ligase. Supporting Evidence: PMID:12852858 We report that the E3 ubiquitin ligase Neuralized localizes asymmetrically in the dividing pI cell and unequally segregates into the pIIb cell, like the Notch inhibitor Numb. PMID:28400441 Neuralized (Neur) is a conserved membrane-associated E3 ubiquitin ligase |
| GO:0005768 endosome | IDA PMID:17065551 The NHR1 domain of Neuralized binds Delta and mediates Delta... | KEEP AS NON CORE | Summary: Neur colocalizes with Hrs-positive endosomes in salivary gland cells. Reason: Colocalization reflects Neur trafficking with its endocytosed substrate Delta; plasma membrane is the primary site of action. Supporting Evidence: PMID:17065551 As a control, we analyzed the degree of colocalization between Hrs and GFP and found little colocalization (quantified in Figure 3 C and data not shown), suggesting the bona fide presence of V5-Neur PA in Hrs-positive endosomes. |
| GO:0005829 cytosol | TAS Reactome:R-DME-209226 | KEEP AS NON CORE | Summary: Reactome places the Neur/Mib1 ubiquitination of DL/SER in the cytosol. Reason: Neur acts on the cytosolic face of the plasma membrane on the ligand intracellular domain; cytosol is acceptable but plasma membrane better describes its site of action. Supporting Evidence: PMID:28400441 Neuralized (Neur) is a conserved membrane-associated E3 ubiquitin ligase |
| GO:0005886 plasma membrane | IDA PMID:10970873 Neuralized functions cell autonomously to regulate Drosophil... | ACCEPT | Summary: Neur localizes to the plasma membrane, which is required for its activity. Reason: Multiple independent IDA studies; membrane targeting is mediated by the phosphoinositide-binding motif and by binding to Delta. Supporting Evidence: PMID:10970873 We show that Neu protein is localized primarily at the plasma membrane. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:18061562 We show that interactions between phosphoinositides and Neuralized contribute to the membrane localization of Neuralized in the absence of Delta, and that the phosphoinositide-binding motif is required for Neuralized to endocytose Delta downstream of Delta ubiquitination. |
| GO:0005886 plasma membrane | IDA PMID:11696324 Neuralized functions as an E3 ubiquitin ligase during Drosop... | ACCEPT | Summary: Neur localizes to the plasma membrane, which is required for its activity. Reason: Multiple independent IDA studies; membrane targeting is mediated by the phosphoinositide-binding motif and by binding to Delta. Supporting Evidence: PMID:10970873 We show that Neu protein is localized primarily at the plasma membrane. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:18061562 We show that interactions between phosphoinositides and Neuralized contribute to the membrane localization of Neuralized in the absence of Delta, and that the phosphoinositide-binding motif is required for Neuralized to endocytose Delta downstream of Delta ubiquitination. |
| GO:0005886 plasma membrane | IDA PMID:17065551 The NHR1 domain of Neuralized binds Delta and mediates Delta... | ACCEPT | Summary: Neur localizes to the plasma membrane, which is required for its activity. Reason: Multiple independent IDA studies; membrane targeting is mediated by the phosphoinositide-binding motif and by binding to Delta. Supporting Evidence: PMID:10970873 We show that Neu protein is localized primarily at the plasma membrane. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:18061562 We show that interactions between phosphoinositides and Neuralized contribute to the membrane localization of Neuralized in the absence of Delta, and that the phosphoinositide-binding motif is required for Neuralized to endocytose Delta downstream of Delta ubiquitination. |
| GO:0005886 plasma membrane | IDA PMID:18061562 Neuralized contains a phosphoinositide-binding motif require... | ACCEPT | Summary: Neur localizes to the plasma membrane, which is required for its activity. Reason: Multiple independent IDA studies; membrane targeting is mediated by the phosphoinositide-binding motif and by binding to Delta. Supporting Evidence: PMID:10970873 We show that Neu protein is localized primarily at the plasma membrane. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:18061562 We show that interactions between phosphoinositides and Neuralized contribute to the membrane localization of Neuralized in the absence of Delta, and that the phosphoinositide-binding motif is required for Neuralized to endocytose Delta downstream of Delta ubiquitination. |
| GO:0007399 nervous system development | IMP PMID:11180964 neuralized functions cell-autonomously to regulate a subset ... | KEEP AS NON CORE | Summary: neur loss-of-function causes neurogenic phenotypes. Reason: Very general developmental process; neur contributes through Notch-mediated lateral inhibition. Retained as non-core. Supporting Evidence: PMID:11180964 We find that neu is required cell-autonomously for lateral inhibition during peripheral neurogenesis and for multiple asymmetric cell divisions in the sensory lineage. |
| GO:0007400 neuroblast fate determination | IMP PMID:28306050 A late role for a subset of neurogenic genes to limit sensor... | KEEP AS NON CORE | Summary: neur mutants show excess sensory precursors, reflecting failure of Notch-mediated lateral inhibition. Reason: Downstream developmental consequence of ligand activation; non-core. Supporting Evidence: PMID:28306050 We have found that the loss of function of all the seven neurogenic loci that were tested causes an increase in replicating sensory precursor cells, consistent with the model that these neurogenic genes normally participate in the process of restricting the number of neuronal precursors. |
| GO:0007419 ventral cord development | HMP PMID:26092715 Novel Genes Involved in Controlling Specification of Drosoph... | KEEP AS NON CORE | Summary: neur alleles were recovered in a forward screen for FMRFa-eGFP (Ap4 neuron) specification in the ventral nerve cord. Reason: High-throughput mutant phenotype (HMP) consistent with the neurogenic role of neur; pleiotropic developmental consequence of Notch pathway function; non-core. Supporting Evidence: PMID:26092715 To this end, we have conducted a forward genetic screen utilizing an Ap4-specific FMRFa-eGFP transgenic reporter as our readout. |
| GO:0007422 peripheral nervous system development | IMP PMID:11180964 neuralized functions cell-autonomously to regulate a subset ... | KEEP AS NON CORE | Summary: neur is required for peripheral nervous system (sensory organ) patterning. Reason: Developmental consequence of Neur-dependent Delta signalling in lateral inhibition and SOP lineage divisions; non-core. Supporting Evidence: PMID:11180964 We find that neu is required cell-autonomously for lateral inhibition during peripheral neurogenesis and for multiple asymmetric cell divisions in the sensory lineage. PMID:8060613 Through a systematic genetic screen, we have identified 55 mutations that affect the development of the PNS of Drosophila embryos. |
| GO:0007422 peripheral nervous system development | IMP PMID:8060613 Mutations affecting the pattern of the PNS in Drosophila rev... | KEEP AS NON CORE | Summary: neur is required for peripheral nervous system (sensory organ) patterning. Reason: Developmental consequence of Neur-dependent Delta signalling in lateral inhibition and SOP lineage divisions; non-core. Supporting Evidence: PMID:11180964 We find that neu is required cell-autonomously for lateral inhibition during peripheral neurogenesis and for multiple asymmetric cell divisions in the sensory lineage. PMID:8060613 Through a systematic genetic screen, we have identified 55 mutations that affect the development of the PNS of Drosophila embryos. |
| GO:0007423 sensory organ development | IMP PMID:10970873 Neuralized functions cell autonomously to regulate Drosophil... | KEEP AS NON CORE | Summary: neur clones show cell-fate defects throughout sense organ development. Reason: Developmental consequence of Notch ligand activation; non-core. Supporting Evidence: PMID:10970873 We find that neu is required for determination of cell fates within the proneural cluster and that cells mutant for neu autonomously adopt neural fates when adjacent to wild-type cells. |
| GO:0007476 imaginal disc-derived wing morphogenesis | IMP PMID:15829515 The ubiquitin ligase Drosophila Mind bomb promotes Notch sig... | KEEP AS NON CORE | Summary: Wing phenotypes in neur/mib1 genetic analyses. Reason: neur is largely dispensable for wing margin formation (Mib1 is the main ligand E3 there), but contributes redundantly and in wing vein lateral inhibition; non-core. Supporting Evidence: PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:11180964 In contrast, neu is apparently dispensable for other N-mediated processes, including lateral inhibition during wing vein development and wing margin induction. |
| GO:0007498 mesoderm development | IMP PMID:1913825 A role for the Drosophila neurogenic genes in mesoderm diffe... | KEEP AS NON CORE | Summary: neur mutant embryos overproduce nautilus-expressing mesodermal cells. Reason: Pleiotropic neurogenic-class phenotype reflecting Notch signalling in mesoderm; non-core. Supporting Evidence: PMID:1913825 Embryonic cells that express the muscle-specific gene nautilus are overproduced in each of seven neurogenic mutants (Notch, Delta, Enhancer of split, big brain, mastermind, neuralized, and almondex), at the apparent expense of neighboring, nonexpressing mesodermal cells. |
| GO:0007616 long-term memory | IMP PMID:18794519 Neuralized is expressed in the alpha/beta lobes of adult Dro... | KEEP AS NON CORE | Summary: neur dosage in mushroom body alpha/beta neurons limits olfactory long-term memory formation. Reason: Genuine IMP but not tied to a defined molecular mechanism; retained as non-core. Supporting Evidence: PMID:18794519 We show that loss of one copy of neur gene results in significant LTM impairment, whereas overexpression of Neur in the peripheral neurons of the alpha/beta lobes of the adult MBs results in a dosage-dependent enhancement of LTM. |
| GO:0008104 intracellular protein localization | IMP PMID:15901829 Regulation of membrane localization of Sanpodo by lethal gia... | KEEP AS NON CORE | Summary: neur is required for internalization of Sanpodo in the SOP lineage. Reason: Downstream of Neur-dependent endocytosis; the term is broad but acceptable as non-core. Supporting Evidence: PMID:15901829 Conversely, the E3 ubiquitin ligase neuralized is required for both Delta endocytosis and the internalization of Sanpodo. |
| GO:0008270 zinc ion binding | ISM PMID:21912646 Comprehensively surveying structure and function of RING dom... | KEEP AS NON CORE | Summary: Neur has a C-terminal RING (C3HC4) zinc finger. Reason: Structural zinc binding by the RING domain is expected; not the functionally informative activity. Supporting Evidence: PMID:21912646 Using a complete set of RING domains from Drosophila melanogaster, all the solved RING domains and cocrystal structures of RING-containing ubiquitin-ligases (RING-E3) and ubiquitin-conjugating enzyme (E2) pairs, we analyzed RING domains structures from their primary to quarternary structures. |
| GO:0008356 asymmetric cell division | IMP PMID:12852858 Unequal segregation of Neuralized biases Notch activation du... | KEEP AS NON CORE | Summary: Neur segregates asymmetrically to pIIb and biases Notch activation during SOP asymmetric division. Reason: Neur acts as a segregating fate determinant that promotes Delta endocytosis in pIIb; the division machinery itself is not Neur's activity, so retained as non-core. Supporting Evidence: PMID:12852858 We report that the E3 ubiquitin ligase Neuralized localizes asymmetrically in the dividing pI cell and unequally segregates into the pIIb cell, like the Notch inhibitor Numb. PMID:12852858 Furthermore, Neuralized upregulates endocytosis of the Notch ligand Delta in the pIIb cell and acts in the pIIb cell to promote activation of Notch in the pIIa cell. |
| GO:0008593 regulation of Notch signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000276953) for regulation of Notch signaling in the Neuralized family. Reason: Neur is a positive regulator of Notch signalling via DSL ligand ubiquitination. The IBA is sound; GO:0045747 (positive) is the more precise term, supported experimentally. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. |
| GO:0016360 sensory organ precursor cell fate determination | IDA PMID:26659188 Polarized endosome dynamics by spindle asymmetry during asym... | KEEP AS NON CORE | Summary: SOP fate/asymmetric Notch signalling context (Sara endosome paper). Reason: The cached abstract is about Sara endosome segregation in SOP division; the curator's full-text reading presumably involved Neur/Delta trafficking. Consistent with Neur's established role; non-core developmental process. Supporting Evidence: PMID:26659188 Biased dispatch of Sara endosomes mediates asymmetric Notch/Delta signalling during the asymmetric division of sensory organ precursors in Drosophila. |
| GO:0016360 sensory organ precursor cell fate determination | IMP PMID:10970873 Neuralized functions cell autonomously to regulate Drosophil... | KEEP AS NON CORE | Summary: neur is required for SOP selection and SOP-lineage fate decisions. Reason: Developmental outcome of Neur-dependent Delta activation in lateral inhibition; non-core. Supporting Evidence: PMID:10970873 We find that neu is required for determination of cell fates within the proneural cluster and that cells mutant for neu autonomously adopt neural fates when adjacent to wild-type cells. PMID:11180964 We find that neu is required cell-autonomously for lateral inhibition during peripheral neurogenesis and for multiple asymmetric cell divisions in the sensory lineage. |
| GO:0016360 sensory organ precursor cell fate determination | IMP PMID:15829515 The ubiquitin ligase Drosophila Mind bomb promotes Notch sig... | KEEP AS NON CORE | Summary: neur is required for SOP selection and SOP-lineage fate decisions. Reason: Developmental outcome of Neur-dependent Delta activation in lateral inhibition; non-core. Supporting Evidence: PMID:10970873 We find that neu is required for determination of cell fates within the proneural cluster and that cells mutant for neu autonomously adopt neural fates when adjacent to wild-type cells. PMID:11180964 We find that neu is required cell-autonomously for lateral inhibition during peripheral neurogenesis and for multiple asymmetric cell divisions in the sensory lineage. |
| GO:0030718 germ-line stem cell population maintenance | IMP PMID:17070683 Stem cells signal to the niche through the Notch pathway in ... | KEEP AS NON CORE | Summary: Germline-derived Delta/Serrate signalling to the niche maintains GSCs; neur was assayed as part of the signal-sending machinery. Reason: The cached abstract does not mention neur explicitly; the full text was seen by the curator. Consistent with Neur's role in ligand activation; non-core. Supporting Evidence: PMID:17070683 Conversely, when GCSs do not produce functional Notch ligands, Delta and Serrate, the TGF-beta pathway is not activated in the GSCs, and they differentiate and subsequently leave the niche. |
| GO:0035204 negative regulation of lamellocyte differentiation | IMP PMID:24318532 An unexpected link between notch signaling and ROS in restri... | KEEP AS NON CORE | Summary: neur knockdown increases lamellocyte differentiation in the lymph gland. Reason: Downstream developmental consequence of Notch signalling; non-core. Supporting Evidence: PMID:24318532 Using RNA interference knockdown of N, Serrate, and neuralized (neur), and twin clone analysis of a N null allele, we show that all three genes inhibit lamellocyte differentiation. |
| GO:0045314 regulation of compound eye photoreceptor development | IMP PMID:15113404 The roles of cis-inactivation by Notch ligands and of neural... | KEEP AS NON CORE | Summary: neur acts non-autonomously in signal-sending cells in eye patterning. Reason: Developmental consequence of Neur-dependent Delta signalling; non-core. Supporting Evidence: PMID:15113404 Neuralized was found to act cell nonautonomously in signal-sending cells during eye development, inconsistent with the view that Neuralized antagonizes cis-inactivation in non-neural cells. |
| GO:0045747 positive regulation of Notch signaling pathway | IGI PMID:15760269 Two distinct E3 ubiquitin ligases have complementary functio... | ACCEPT | Summary: Neur positively regulates Notch signalling by ubiquitinating and promoting endocytosis of DSL ligands in signal-sending cells. Reason: Central, repeatedly demonstrated biological role (IMP/IGI with Dl, Ser, mib1). Neur acts in the signal-sending cell to activate ligand. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:15930117 Here, we present evidence that the Drosophila ortholog of Mib (Dmib) is required for ubiquitination and signaling activity of DSL ligands in cells that normally do not express Neur, and can be functionally replaced by ectopically expressed Neur. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). PMID:15760269 We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila. PMID:28960177 Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. |
| GO:0045747 positive regulation of Notch signaling pathway | IGI PMID:16093323 The interplay between DSL proteins and ubiquitin ligases in ... | ACCEPT | Summary: Neur positively regulates Notch signalling by ubiquitinating and promoting endocytosis of DSL ligands in signal-sending cells. Reason: Central, repeatedly demonstrated biological role (IMP/IGI with Dl, Ser, mib1). Neur acts in the signal-sending cell to activate ligand. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:15930117 Here, we present evidence that the Drosophila ortholog of Mib (Dmib) is required for ubiquitination and signaling activity of DSL ligands in cells that normally do not express Neur, and can be functionally replaced by ectopically expressed Neur. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). PMID:15760269 We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila. PMID:28960177 Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. |
| GO:0045747 positive regulation of Notch signaling pathway | IGI PMID:22162135 Distinct intracellular motifs of Delta mediate its ubiquityl... | ACCEPT | Summary: Neur positively regulates Notch signalling by ubiquitinating and promoting endocytosis of DSL ligands in signal-sending cells. Reason: Central, repeatedly demonstrated biological role (IMP/IGI with Dl, Ser, mib1). Neur acts in the signal-sending cell to activate ligand. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:15930117 Here, we present evidence that the Drosophila ortholog of Mib (Dmib) is required for ubiquitination and signaling activity of DSL ligands in cells that normally do not express Neur, and can be functionally replaced by ectopically expressed Neur. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). PMID:15760269 We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila. PMID:28960177 Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. |
| GO:0045747 positive regulation of Notch signaling pathway | IGI PMID:28960177 Ubiquitylation-independent activation of Notch signalling by... | ACCEPT | Summary: Neur positively regulates Notch signalling by ubiquitinating and promoting endocytosis of DSL ligands in signal-sending cells. Reason: Central, repeatedly demonstrated biological role (IMP/IGI with Dl, Ser, mib1). Neur acts in the signal-sending cell to activate ligand. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:15930117 Here, we present evidence that the Drosophila ortholog of Mib (Dmib) is required for ubiquitination and signaling activity of DSL ligands in cells that normally do not express Neur, and can be functionally replaced by ectopically expressed Neur. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). PMID:15760269 We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila. PMID:28960177 Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. |
| GO:0045747 positive regulation of Notch signaling pathway | IMP PMID:15829515 The ubiquitin ligase Drosophila Mind bomb promotes Notch sig... | ACCEPT | Summary: Neur positively regulates Notch signalling by ubiquitinating and promoting endocytosis of DSL ligands in signal-sending cells. Reason: Central, repeatedly demonstrated biological role (IMP/IGI with Dl, Ser, mib1). Neur acts in the signal-sending cell to activate ligand. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:15930117 Here, we present evidence that the Drosophila ortholog of Mib (Dmib) is required for ubiquitination and signaling activity of DSL ligands in cells that normally do not express Neur, and can be functionally replaced by ectopically expressed Neur. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). PMID:15760269 We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila. PMID:28960177 Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. |
| GO:0045747 positive regulation of Notch signaling pathway | IMP PMID:15930117 Distinct roles for Mind bomb, Neuralized and Epsin in mediat... | ACCEPT | Summary: Neur positively regulates Notch signalling by ubiquitinating and promoting endocytosis of DSL ligands in signal-sending cells. Reason: Central, repeatedly demonstrated biological role (IMP/IGI with Dl, Ser, mib1). Neur acts in the signal-sending cell to activate ligand. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:15930117 Here, we present evidence that the Drosophila ortholog of Mib (Dmib) is required for ubiquitination and signaling activity of DSL ligands in cells that normally do not express Neur, and can be functionally replaced by ectopically expressed Neur. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). PMID:15760269 We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila. PMID:28960177 Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. |
| GO:0045747 positive regulation of Notch signaling pathway | IMP PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | ACCEPT | Summary: Neur positively regulates Notch signalling by ubiquitinating and promoting endocytosis of DSL ligands in signal-sending cells. Reason: Central, repeatedly demonstrated biological role (IMP/IGI with Dl, Ser, mib1). Neur acts in the signal-sending cell to activate ligand. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:16093323 Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling. PMID:15829515 We conclude that ubiquitination of Delta and Serrate by Neuralized and D-mib is an obligate feature of DSL ligand activation throughout Drosophila development. PMID:15930117 Here, we present evidence that the Drosophila ortholog of Mib (Dmib) is required for ubiquitination and signaling activity of DSL ligands in cells that normally do not express Neur, and can be functionally replaced by ectopically expressed Neur. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). PMID:15760269 We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila. PMID:28960177 Neur, which is needed for these processes, was shown to be able to activate Dl in an ubi-independent manner. |
| GO:0045807 positive regulation of endocytosis | IMP PMID:16093323 The interplay between DSL proteins and ubiquitin ligases in ... | ACCEPT | Summary: Neur promotes endocytosis of Delta and Serrate. Reason: Direct experimental observation of Neur-driven ligand internalization; mechanistically part of ligand activation. Supporting Evidence: PMID:16093323 Neuralized physically associates with Serrate and stimulates its endocytosis and signaling activity. PMID:19580805 we show that Neur-dependent endocytosis of Dl requires the integrity of its NXXN motif. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). |
| GO:0045807 positive regulation of endocytosis | IMP PMID:16459303 Bearded family members inhibit Neuralized-mediated endocytos... | ACCEPT | Summary: Neur promotes endocytosis of Delta and Serrate. Reason: Direct experimental observation of Neur-driven ligand internalization; mechanistically part of ligand activation. Supporting Evidence: PMID:16093323 Neuralized physically associates with Serrate and stimulates its endocytosis and signaling activity. PMID:19580805 we show that Neur-dependent endocytosis of Dl requires the integrity of its NXXN motif. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). |
| GO:0045807 positive regulation of endocytosis | IMP PMID:19580805 Both inhibition and activation of Notch signaling rely on a ... | ACCEPT | Summary: Neur promotes endocytosis of Delta and Serrate. Reason: Direct experimental observation of Neur-driven ligand internalization; mechanistically part of ligand activation. Supporting Evidence: PMID:16093323 Neuralized physically associates with Serrate and stimulates its endocytosis and signaling activity. PMID:19580805 we show that Neur-dependent endocytosis of Dl requires the integrity of its NXXN motif. PMID:16459303 In Drosophila, the E3 ubiquitin ligase Neuralized (Neur) promotes the endocytosis and signaling activity of the ligand Delta (Dl). |
| GO:0046532 regulation of photoreceptor cell differentiation | IMP PMID:15113404 The roles of cis-inactivation by Notch ligands and of neural... | KEEP AS NON CORE | Summary: neur regulates photoreceptor (R8) differentiation. Reason: Developmental consequence of Neur-dependent Delta signalling; non-core. Supporting Evidence: PMID:15113404 Neuralized was found to act cell nonautonomously in signal-sending cells during eye development, inconsistent with the view that Neuralized antagonizes cis-inactivation in non-neural cells. PMID:11344304 Neur is required in a cell-autonomous fashion to restrict R8 and other photoreceptor fates and is involved in lateral inhibition of interommatidial bristles but is not required for induction of the cone cell fate. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:12852858 Unequal segregation of Neuralized biases Notch activation du... | KEEP AS NON CORE | Summary: Neur localizes to perinuclear/cortical regions in dividing SOPs. Reason: Localization snapshot; non-core relative to plasma membrane. Supporting Evidence: PMID:12852858 We report that the E3 ubiquitin ligase Neuralized localizes asymmetrically in the dividing pI cell and unequally segregates into the pIIb cell, like the Notch inhibitor Numb. |
| GO:0048749 compound eye development | IMP PMID:11344304 Neuralized is essential for a subset of Notch pathway-depend... | KEEP AS NON CORE | Summary: neur is required for a subset of Notch-dependent cell fate decisions in eye development. Reason: Developmental consequence; non-core. Supporting Evidence: PMID:11344304 Neur is required in a cell-autonomous fashion to restrict R8 and other photoreceptor fates and is involved in lateral inhibition of interommatidial bristles but is not required for induction of the cone cell fate. |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Neur is a RING-type E3 ubiquitin ligase that ubiquitinates the intracellular domains of Delta and Serrate. Reason: Core molecular function, supported by direct biochemical assays and by the PAINT IBA (PTN004361013) across the Neuralized family. Supporting Evidence: PMID:11740940 In this report, we present genetic and biochemical evidence that Neur is a RING-type, E3 ubiquitin ligase. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:22162135 Using a cell-based assay, we detected ubiquitylation of Dl by both Neur and Mib1. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:11696324 Neuralized functions as an E3 ubiquitin ligase during Drosop... | ACCEPT | Summary: Neur is a RING-type E3 ubiquitin ligase that ubiquitinates the intracellular domains of Delta and Serrate. Reason: Core molecular function, supported by direct biochemical assays and by the PAINT IBA (PTN004361013) across the Neuralized family. Supporting Evidence: PMID:11740940 In this report, we present genetic and biochemical evidence that Neur is a RING-type, E3 ubiquitin ligase. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:22162135 Using a cell-based assay, we detected ubiquitylation of Dl by both Neur and Mib1. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:11740940 Drosophila neuralized is a ubiquitin ligase that promotes th... | ACCEPT | Summary: Neur is a RING-type E3 ubiquitin ligase that ubiquitinates the intracellular domains of Delta and Serrate. Reason: Core molecular function, supported by direct biochemical assays and by the PAINT IBA (PTN004361013) across the Neuralized family. Supporting Evidence: PMID:11740940 In this report, we present genetic and biochemical evidence that Neur is a RING-type, E3 ubiquitin ligase. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:22162135 Using a cell-based assay, we detected ubiquitylation of Dl by both Neur and Mib1. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:22162135 Distinct intracellular motifs of Delta mediate its ubiquityl... | ACCEPT | Summary: Neur is a RING-type E3 ubiquitin ligase that ubiquitinates the intracellular domains of Delta and Serrate. Reason: Core molecular function, supported by direct biochemical assays and by the PAINT IBA (PTN004361013) across the Neuralized family. Supporting Evidence: PMID:11740940 In this report, we present genetic and biochemical evidence that Neur is a RING-type, E3 ubiquitin ligase. PMID:11696324 Here, we show that Neu is required at the plasma membrane for functional activity and that its RING finger domain acts as an E3 ubiquitin ligase. PMID:22162135 Using a cell-based assay, we detected ubiquitylation of Dl by both Neur and Mib1. |
| GO:0070086 ubiquitin-dependent endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000276953): Neuralized family proteins drive ubiquitin-dependent endocytosis of their substrates. Reason: Neur ubiquitinates Delta and thereby routes it into an Epsin-dependent endocytic pathway; its phosphoinositide-binding motif is additionally required for Delta endocytosis downstream of ubiquitination, so Neur does work in this process. Supporting Evidence: PMID:11740940 Collectively, our data indicate that Neur is a ubiquitin ligase that positively regulates the N pathway by promoting the endocytosis and degradation of Dl. PMID:18061562 We show that interactions between phosphoinositides and Neuralized contribute to the membrane localization of Neuralized in the absence of Delta, and that the phosphoinositide-binding motif is required for Neuralized to endocytose Delta downstream of Delta ubiquitination. |
| GO:1901981 phosphatidylinositol phosphate binding | IDA PMID:18061562 Neuralized contains a phosphoinositide-binding motif require... | ACCEPT | Summary: Neur binds phosphoinositides through a basic motif required for membrane localization and Delta endocytosis. Reason: Direct in vitro binding plus functional mutant analysis. Supporting Evidence: PMID:18061562 Through in vitro binding assays we have identified an interaction between Neuralized and phosphoinositides, modified membrane lipids that mediate membrane trafficking and signaling. PMID:18061562 We show that interactions between phosphoinositides and Neuralized contribute to the membrane localization of Neuralized in the absence of Delta, and that the phosphoinositide-binding motif is required for Neuralized to endocytose Delta downstream of Delta ubiquitination. |
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Download this section (compressed HTML)Q: Is multi-monoubiquitylation or K63-linked polyubiquitylation of the Delta ICD the signalling-relevant Neur product in vivo?
Q: How does Neur activate Delta in the ubiquitylation-independent mode reported for some lateral inhibition events?
Experiment: Ubiquitin-linkage-specific mass spectrometry of Delta ICD from SOPs expressing endogenous Neur versus Mib1, with lysine-less Delta rescue.
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Download this section (compressed HTML)neuralized (neur) encodes an E3 ubiquitin ligase of the RING family. It is part of the Notch signaling pathway, where it is thought to contribute to the endocytosis-dependent activation of the ligand. It also has Notch-independent functions in epithelial morphogenesis.
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