Notch signaling is a juxtacrine pathway in which the transmembrane ligands Delta and Serrate on one cell bind the Notch receptor on a neighbouring cell. Ligand binding, together with ligand endocytosis in the signal-sending cell, exposes Notch to cleavage by the ADAM10 metalloprotease Kuzbanian (S2 cleavage), after which the gamma-secretase complex (Presenilin, Nicastrin, Aph-1 and Pen-2) cleaves within the transmembrane domain (S3 cleavage) and releases the Notch intracellular domain. The intracellular domain enters the nucleus and forms a transcriptional activation complex with the CSL DNA-binding protein Suppressor of Hairless and the coactivator Mastermind, switching Su(H) target genes such as the Enhancer of split complex genes from repression to activation. The pathway controls lateral inhibition, boundary formation and binary cell-fate decisions throughout development.
Boundary. The module contains ligands, receptor, the two proteolytic steps and the nuclear CSL complex. Notch appears twice, as the receptor and as the intracellular domain within the nuclear complex. E3 ligases that drive ligand endocytosis (Neuralized, Mind bomb 1), glycosyltransferases that modify Notch (Ofut1, Fringe, Rumi), the corepressor Hairless and the Enhancer of split target genes are FlyBase regulators and are not modelled as parts. Weary (wry) is included because FlyBase lists it among the core components, but its mechanism is not established. FlyBase groups realized by this module: CNM (FBgg0001066), NTCH (FBgg0001068). Subgroups folded into it: NTCH-C. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: NTCH-N (negative regulators of notch signaling pathway, 37 genes); NTCH-P (positive regulators of notch signaling pathway, 48 genes). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_notch_signaling.yaml. Member genes with a gene review in this repository: aph-1, Delta, kuz, mam, N, Nct, pen-2, Psn, Ser, Su(H), Tace, wry.
All recommended fields populated.
✗ none found
No MODULE:dmel_notch_signaling deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
8 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (8 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| notch_ligands_delta | Delta UniProtKB:P10041 Gene |
Notch binding GO:0005112 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| notch_ligands_ser | Ser UniProtKB:P18168 Gene |
Notch binding GO:0005112 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| notch_receptor_n | N UniProtKB:P07207 Gene |
transmembrane signaling receptor activity GO:0004888 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| s2_cleavage_kuz | kuz UniProtKB:Q9VJW9 Gene |
metalloendopeptidase activity GO:0004222 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| s2_cleavage_tace | Tace UniProtKB:Q9VAC5 Gene |
metalloendopeptidase activity GO:0004222 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| gamma_secretase_complex/psn | Psn UniProtKB:O02194 Complex Unit |
aspartic endopeptidase activity, intramembrane cleaving GO:0042500 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| csl_nicd_mam_complex_complex/su_h | Su(H) UniProtKB:P28159 Complex Unit |
DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| csl_nicd_mam_complex_complex/mam | mam UniProtKB:P21519 Complex Unit |
transcription coactivator activity GO:0003713 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
12 complete review(s) · 12 with deep research · 0 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| aph-1 Q9VQG2 | ✓ | ✓ | ✓ |
| Dl P10041 | ✓ | ✓ | ✓ |
| kuz Q9VJW9 | ✓ | ✓ | ✓ |
| mam P21519 | ✓ | ✓ | ✓ |
| N P07207 | ✓ | ✓ | ✓ |
| Nct Q9VC27 | ✓ | ✓ | ✓ |
| pen-2 Q86BE9 | ✓ | ✓ | ✓ |
| Psn O02194 | ✓ | ✓ | ✓ |
| Ser P18168 | ✓ | ✓ | ✓ |
| Su(H) P28159 | ✓ | ✓ | ✓ |
| Tace Q9VAC5 | ✓ | ✓ | ✓ |
| wry Q7KU08 | ✓ | ✓ | ✓ |
Juxtacrine pathway in which Delta/Serrate binding triggers sequential cleavage of Notch and activation of Su(H)-Mastermind target genes by the Notch intracellular domain.
Transmembrane DSL-domain ligands presented by the signal-sending cell.
Single-pass membrane protein with EGF-like repeats that FlyBase lists among the core components of Notch signaling; how it acts in the pathway is not well characterized.
Kuzbanian (ADAM10) performs the ligand-dependent S2 cleavage of Notch; the ADAM17 homolog Tace also cleaves Notch, mainly in ligand-independent contexts.
The Notch intracellular domain, the CSL DNA-binding protein Suppressor of Hairless and the coactivator Mastermind form the activation complex on Su(H) binding sites of target genes.