Neurogenic locus Notch protein
Also known as: N
Function
Essential signaling protein which has a major role in many developmental processes. Functions as a receptor for membrane-bound ligands Delta and Serrate to regulate cell-fate determination. Upon ligand activation, and releasing from the cell membrane, the Notch intracellular domain (NICD) forms a transcriptional activator complex with Su(H) (Suppressor of hairless) and activates genes of the E(spl) complex. Regulates oogenesis, the differentiation of the ectoderm and the development of the central and peripheral nervous system, eye, wing disk, muscles and segmental appendages such as antennae and legs, through lateral inhibition or induction. Regulates neuroblast self-renewal, identity and proliferation through the regulation of bHLH-O proteins; in larval brains, involved in the maintenance of type II neuroblast self-renewal and identity by suppressing erm expression together with pnt; might also regulate dpn expression through the activation of the transcriptional regulator Su(H). Targeted for ESCRT-mediated endosomal sequestration and lysosomal degradation by various E3 ubiquitin ligases to regulate the Notch signaling pathway. Can undergo ligand-dependent and non-canonical ligand-independent activation. Ligand-independent activation is dependent on endosome acidification and probably occurs in late endosomes or lysosome. Ectopic ligand-independent activation occurs when disruption of the endolysosomal pathway, particularly of the ESCRT-III complex, prevents sequestration of the receptor in intraluminal vesicles of multivesicular bodies.
Classification
- Family (Pfam)
- PF00023 Ank, PF12796 Ank_2, PF00008 EGF, PF07645 EGF_CA, PF25024 EGF_TEN, PF12661 hEGF, PF06816 NOD, PF07684 NODP, PF00066 Notch
- InterPro
- Ankyrin_rpt, Ankyrin_rpt-contain_sf, EGF, EGF-like_Ca-bd_dom, EGF-like_CS, EGF-type_Asp/Asn_hydroxyl_site, EGF_Ca-bd_CS, Growth_fac_rcpt_cys_sf, Notch, Notch-like_dom_sf, NOTCH1_EGF-like, Notch_C, Notch_Cell-Fate_Det, Notch_dom, Notch_NOD_dom, Notch_NODP_dom
- Functional cluster
- Venom Serine Proteases & Phospholipase A2
Experimental structures · PDB · 3
A predicted model is available from AlphaFold.
Gene Ontology · 131
- GO:0005912 adherens junction
- GO:0016324 apical plasma membrane
- GO:0009986 cell surface
- GO:1990433 CSL-Notch-Mastermind transcription factor complex
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005769 early endosome
- GO:0030139 endocytic vesicle
- GO:0005783 endoplasmic reticulum
- GO:0005788 endoplasmic reticulum lumen
- GO:0005768 endosome
- GO:0005796 Golgi lumen
- GO:0005770 late endosome
- GO:0016328 lateral plasma membrane
- GO:0016020 membrane
- GO:0005771 multivesicular body
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0032991 protein-containing complex
- GO:0005509 calcium ion binding
- GO:0003682 chromatin binding
- GO:0035035 histone acetyltransferase binding
- GO:0003713 transcription coactivator activity
- GO:0004888 transmembrane signaling receptor activity
- GO:0050699 WW domain binding
- GO:0007015 actin filament organization
- GO:0008356 asymmetric cell division
- GO:0007411 axon guidance
- GO:0007298 border follicle cell migration
- GO:0043697 cell dedifferentiation
- GO:0030154 cell differentiation
- GO:0045165 cell fate commitment
- GO:0022416 chaeta development
- GO:0008407 chaeta morphogenesis
- GO:0060289 compartment boundary maintenance
- GO:0048749 compound eye development
- GO:0001745 compound eye morphogenesis
- GO:0046667 compound eye retinal cell programmed cell death
- GO:0042688 crystal cell differentiation
- GO:0002213 defense response to insect
- GO:0008340 determination of adult lifespan
- GO:0006351 DNA-templated transcription
- GO:0046843 dorsal appendage formation
- GO:0007391 dorsal closure
- GO:0009950 dorsal/ventral axis specification
- GO:0035162 embryonic hemopoiesis
- GO:0061331 epithelial cell proliferation involved in Malpighian tubule morphogenesis
- GO:0035153 epithelial cell type specification, open tracheal system
- GO:0035214 eye-antennal disc development
- GO:0007455 eye-antennal disc morphogenesis
- GO:0036099 female germ-line stem cell population maintenance
- GO:0030707 follicle cell of egg chamber development
- GO:0007297 follicle cell of egg chamber migration
- GO:0030713 follicle cell of egg chamber stalk formation
- GO:0007440 foregut morphogenesis
- GO:0060288 formation of a compartment boundary
- GO:0030718 germ-line stem cell population maintenance
- GO:0060250 germ-line stem-cell niche homeostasis
- GO:0007293 germarium-derived egg chamber formation
- GO:0010001 glial cell differentiation
- GO:0007403 glial cell fate determination
- GO:0008347 glial cell migration
- GO:0035172 hemocyte proliferation
- GO:0016348 imaginal disc-derived leg joint morphogenesis
- GO:0007480 imaginal disc-derived leg morphogenesis
- GO:0036011 imaginal disc-derived leg segmentation
- GO:0048803 imaginal disc-derived male genitalia morphogenesis
- GO:0008587 imaginal disc-derived wing margin morphogenesis
- GO:0007476 imaginal disc-derived wing morphogenesis
- GO:0007474 imaginal disc-derived wing vein specification
- GO:0036335 intestinal stem cell homeostasis
- GO:0035171 lamellocyte differentiation
- GO:0035167 larval lymph gland hemopoiesis
- GO:0046331 lateral inhibition
- GO:0007478 leg disc morphogenesis
- GO:0007616 long-term memory
- GO:0048542 lymph gland development
- GO:0061382 Malpighian tubule tip cell differentiation
- GO:0007498 mesoderm development
- GO:0060571 morphogenesis of an epithelial fold
- GO:0008045 motor neuron axon guidance
- GO:0046716 muscle cell cellular homeostasis
- GO:0007521 muscle cell fate determination
- GO:0048627 myoblast development
- GO:2000048 negative regulation of cell-cell adhesion mediated by cadherin
- GO:0045316 negative regulation of compound eye photoreceptor development
- GO:0010629 negative regulation of gene expression
- GO:0035204 negative regulation of lamellocyte differentiation
- GO:0050768 negative regulation of neurogenesis
- GO:0050877 nervous system process
- GO:0014019 neuroblast development
- GO:0007400 neuroblast fate determination
- GO:0014018 neuroblast fate specification
- GO:0007405 neuroblast proliferation
- GO:0048664 neuron fate determination
- GO:0048665 neuron fate specification
- GO:0097150 neuronal stem cell population maintenance
- GO:0007219 Notch signaling pathway
- GO:0016318 ommatidial rotation
- GO:0030720 oocyte localization involved in germarium-derived egg chamber formation
- GO:0048477 oogenesis
- GO:0007422 peripheral nervous system development
- GO:0008284 positive regulation of cell population proliferation
- GO:0042691 positive regulation of crystal cell differentiation
- GO:0045893 positive regulation of DNA-templated transcription
- GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
- GO:0010628 positive regulation of gene expression
- GO:0002052 positive regulation of neuroblast proliferation
- GO:0043525 positive regulation of neuron apoptotic process
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0048052 R1/R6 cell differentiation
- GO:0048056 R3/R4 cell differentiation
- GO:0045466 R7 cell differentiation
- GO:0042686 regulation of cardioblast cell fate specification
- GO:0045595 regulation of cell differentiation
- GO:0051489 regulation of filopodium assembly
- GO:0006110 regulation of glycolytic process
- GO:0040008 regulation of growth
- GO:0007346 regulation of mitotic cell cycle
- GO:1902692 regulation of neuroblast proliferation
- GO:0050767 regulation of neurogenesis
- GO:2000035 regulation of stem cell division
- GO:0009608 response to symbiont
- GO:0046666 retinal cell programmed cell death
- GO:0016330 second mitotic wave involved in compound eye morphogenesis
- GO:0007423 sensory organ development
- GO:0016360 sensory organ precursor cell fate determination
- GO:0048863 stem cell differentiation
- GO:0048190 wing disc dorsal/ventral pattern formation
- GO:0035222 wing disc pattern formation
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Neurogenic locus notch homolog protein 1 0.96
- Neurogenic locus notch homolog protein 1 0.95
- Neurogenic locus notch homolog protein 1 0.95
- Neurogenic locus notch homolog protein 1 0.95
- Neurogenic locus notch homolog protein 2 0.94
- Neurogenic locus notch homolog protein 1 0.94
- Neurogenic locus notch homolog protein 1 0.94
- Neurogenic locus notch homolog protein 2 0.94
- Neurogenic locus notch homolog protein 2 0.94
- Neurogenic locus notch homolog protein 1 0.93
- Protein jagged-1 0.88
- Protein jagged-1 0.88
Co-cited proteins · studied together in the literature
- Protein deltex 3 shared papers
- Coiled-coil and C2 domain-containing protein 1-like 6 shared papers
- GDP-fucose protein O-fucosyltransferase 1 4 shared papers
- Presenilin homolog 2 shared papers
- E3 ubiquitin-protein ligase Su(dx) 1 shared papers
- O-glucosyltransferase rumi 1 shared papers
- E3 ubiquitin-protein ligase Nedd-4 2 shared papers
- Homeobox protein prospero 3 shared papers
- Charged multivesicular body protein 4 3 shared papers
- Protein deadpan 3 shared papers
- Fez family zinc finger protein erm 3 shared papers
- GDP-mannose 4,6-dehydratase 2 shared papers
Literature · 42 cited papers
- Lethal (2) giant discs (Lgd)/CC2D1 is required for the full activity of the ESCRT machinery. BMC Biol. · 2020
- AKAP200 promotes Notch stability by protecting it from Cbl/lysosome-mediated degradation in Drosophila melanogaster. PLoS Genet. · 2018
- bHLH-O proteins balance the self-renewal and differentiation of Drosophila neural stem cells by regulating Earmuff expression. Dev. Biol. · 2017
- Mapping sites of O-glycosylation and fringe elongation on Drosophila Notch. J. Biol. Chem. · 2016
- Notch maintains Drosophila type II neuroblasts by suppressing expression of the Fez transcription factor Earmuff. Development · 2016
- Lgd regulates the activity of the BMP/Dpp signalling pathway during Drosophila oogenesis. Development · 2015
- Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila. Mol. Biol. Cell · 2014
- Activation of Notch in lgd mutant cells requires the fusion of late endosomes with the lysosome. J. Cell Sci. · 2013
- The bHLH repressor Deadpan regulates the self-renewal and specification of Drosophila larval neural stem cells independently of Notch. PLoS ONE · 2012
- Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal. J. Cell Biol. · 2011
- The bHLH factor deadpan is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila. Dev. Biol. · 2011
- dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila. Dev. Cell · 2010
- … and 30 more in the literature graph