Protein: Neurogenic locus Notch protein [Cleaved into: Processed neurogenic locus Notch protein] (P07207)
Organism: Drosophila melanogaster (Fruit fly)
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).
Subcellular location: Cell membrane {ECO:0000269|PubMed:17329366}; Single-pass type I membrane protein {ECO:0000269|PubMed:17329366}. Endosome {ECO:0000269|PubMed:17329366}. Endosome, multivesicular body {ECO:0000269|PubMed:22162134}. Note=Transported to early endosomes by O-fut1 (PubMed:17329366). Targeting to the endolysosomal pathway is regulated by protein ubiquitination and reliant on the ESCRT-III complex (PubMed:22162134). Colocalizes with dx/deltex on multivesicular bodies (PubMed:22162134). {ECO:0000269|PubMed:22162134}.; SUBCELLULAR LOCATION: [Processed neurogenic locus Notch protein]: Nucleus. Note=Upon activation and S3 cleavage, it is released from the cell membrane and enters into the nucleus in conjunction with Su(H).
Sequence: MQSQRSRRRSRAPNTWICFWINKMHAVASLPASLPLLLLTLAFANLPNTVRGTDTALVAASCTSVGCQNGGTCVTQLNGKTYCACDSHYVGDYCEHRNPCNSMRCQNGGTCQVTFRNGRPGISCKCPLGFDESLCEIAVPNACDHVTCLNGGTCQLKTLEEYTCACANGYTGERCETKNLCASSPCRNGATCTALAGSSSFTCSCPPGFTGDTCSYDIEECQSNPCKYGGTCVNTHGSYQCMCPTGYTGKDCDTKYKPCSPSPCQNGGICRSNGLSYECKCPKGFEGKNCEQNYDDCLGHLCQNGGTCIDGISDYTCRCPPNFTGRFCQDDVDECAQRDHPVCQNGATCTNTHGSYSCICVNGWAGLDCSNNTDDCKQAACFYGATCIDGVGSFYCQCTKGKTGLLCHLDDACTSNPCHADAICDTSPINGSYACSCATGYKGVDCSEDIDECDQGSPCEHNGICVNTPGSYRCNCSQGFTGPRCETNINECESHPCQNEGSCLDDPGTFRCVCMPGFTGTQCEIDIDECQSNPCLNDGTCHDKINGFKCSCALGFTGARCQINIDDCQSQPCRNRGICHDSIAGYSCECPPGYTGTSCEININDCDSNPCHRGKCIDDVNSFKCLCDPGYTGYICQKQINECESNPCQFDGHCQDRVGSYYCQCQAGTSGKNCEVNVNECHSNPCNNGATCIDGINSYKCQCVPGFTGQHCEKNVDECISSPCANNGVCIDQVNGYKCECPRGFYDAHCLSDVDECASNPCVNEGRCEDGINEFICHCPPGYTGKRCELDIDECSSNPCQHGGTCYDKLNAFSCQCMPGYTGQKCETNIDDCVTNPCGNGGTCIDKVNGYKCVCKVPFTGRDCESKMDPCASNRCKNEAKCTPSSNFLDFSCTCKLGYTGRYCDEDIDECSLSSPCRNGASCLNVPGSYRCLCTKGYEGRDCAINTDDCASFPCQNGGTCLDGIGDYSCLCVDGFDGKHCETDINECLSQPCQNGATCSQYVNSYTCTCPLGFSGINCQTNDEDCTESSCLNGGSCIDGINGYNCSCLAGYSGANCQYKLNKCDSNPCLNGATCHEQNNEYTCHCPSGFTGKQCSEYVDWCGQSPCENGATCSQMKHQFSCKCSAGWTGKLCDVQTISCQDAADRKGLSLRQLCNNGTCKDYGNSHVCYCSQGYAGSYCQKEIDECQSQPCQNGGTCRDLIGAYECQCRQGFQGQNCELNIDDCAPNPCQNGGTCHDRVMNFSCSCPPGTMGIICEINKDDCKPGACHNNGSCIDRVGGFECVCQPGFVGARCEGDINECLSNPCSNAGTLDCVQLVNNYHCNCRPGHMGRHCEHKVDFCAQSPCQNGGNCNIRQSGHHCICNNGFYGKNCELSGQDCDSNPCRVGNCVVADEGFGYRCECPRGTLGEHCEIDTLDECSPNPCAQGAACEDLLGDYECLCPSKWKGKRCDIYDANYPGWNGGSGSGNDRYAADLEQQRAMCDKRGCTEKQGNGICDSDCNTYACNFDGNDCSLGINPWANCTANECWNKFKNGKCNEECNNAACHYDGHDCERKLKSCDSLFDAYCQKHYGDGFCDYGCNNAECSWDGLDCENKTQSPVLAEGAMSVVMLMNVEAFREIQAQFLRNMSHMLRTTVRLKKDALGHDIIINWKDNVRVPEIEDTDFARKNKILYTQQVHQTGIQIYLEIDNRKCTECFTHAVEAAEFLAATAAKHQLRNDFQIHSVRGIKNPGDEDNGEPPANVKYVITGIILVIIALAFFGMVLSTQRKRAHGVTWFPEGFRAPAAVMSRRRRDPHGQEMRNLNKQVAMQSQGVGQPGAHWSDDESDMPLPKRQRSDPVSGVGLGNNGGYASDHTMVSEYEEADQRVWSQAHLDVVDVRAIMTPPAHQDGGKHDVDARGPCGLTPLMIAAVRGGGLDTGEDIENNEDSTAQVISDLLAQGAELNATMDKTGETSLHLAARFARADAAKRLLDAGADANCQDNTGRTPLHAAVAADAMGVFQILLRNRATNLNARMHDGTTPLILAARLAIEGMVEDLITADADINAADNSGKTALHWAAAVNNTEAVNILLMHHANRDAQDDKDETPLFLAAREGSYEACKALLDNFANREITDHMDRLPRDVASERLHHDIVRLLDEHVPRSPQMLSMTPQAMIGSPPPGQQQPQLITQPTVISAGNGGNNGNGNASGKQSNQTAKQKAAKKAKLIEGSPDNGLDATGSLRRKASSKKTSAASKKAANLNGLNPGQLTGGVSGVPGVPPTNSAAQAAAAAAAAVAAMSHELEGSPVGVGMGGNLPSPYDTSSMYSNAMAAPLANGNPNTGAKQPPSYEDCIKNAQSMQSLQGNGLDMIKLDNYAYSMGSPFQQELLNGQGLGMNGNGQRNGVGPGVLPGGLCGMGGLSGAGNGNSHEQGLSPPYSNQSPPHSVQSSLALSPHAYLGSPSPAKSRPSLPTSPTHIQAMRHATQQKQFGGSNLNSLLGGANGGGVVGGGGGGGGGVGQGPQNSPVSLGIISPTGSDMGIMLAPPQSSKNSAIMQTISPQQQQQQQQQQQQQHQQQQQQQQQQQQQQQQQLGGLEFGSAGLDLNGFCGSPDSFHSGQMNPPSIQSSMSGSSPSTNMLSPSSQHNQQAFYQYLTPSSQHSGGHTPQHLVQTLDSYPTPSPESPGHWSSSSPRSNSDWSEGVQSPAANNLYISGGHQANKGSEAIYI
InterPro domains: - IPR051022: Notch Signaling and Cell Fate Determination (family) [555-780]
- IPR001881: EGF-like calcium-binding domain (domain) [96-1451]
- IPR011656: Notch, NODP domain (domain) [1678-1736]
- IPR024600: Notch, C-terminal (domain) [2626-2683]
- IPR036770: Ankyrin repeat-containing domain superfamily (homologous_superfamily) [1892-2143]
- IPR018097: EGF-like calcium-binding, conserved site (conserved_site) [217-1283]
- IPR000152: EGF-type aspartate/asparagine hydroxylation site (ptm) [232-1441]
- IPR049883: NOTCH1 EGF-like calcium-binding domain (domain) [331-481]
- IPR013032: EGF-like, conserved site (conserved_site) [302-1052]
- IPR002110: Ankyrin repeat (repeat) [1901-2146]
- IPR000800: Notch domain (domain) [1475-1599]
- IPR000742: EGF-like domain (domain) [58-1451]
- IPR009030: Growth factor receptor cysteine-rich domain superfamily (homologous_superfamily) [205-1344]
- IPR035993: Notch-like domain superfamily (homologous_superfamily) [1481-1593]
- IPR008297: Notch (family) [27-2702]
- IPR010660: Notch, NOD domain (domain) [1598-1654]
Interaction partners: - Suppressor of hairless protein
- Protein serrate
- Neurogenic locus protein delta
- Protein numb
- Protein deltex
- Presenilin homolog
- Fringe glycosyltransferase
- Nicastrin
- Neurogenic protein mastermind
- Segment polarity protein dishevelled
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0060089 (molecular transducer activity), GO:0038023 (signaling receptor activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0022414 (reproductive process), GO:0040007 (growth), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0019953 (sexual reproduction), GO:0048589 (developmental growth), GO:0048856 (anatomical structure development), GO:0009653 (anatomical structure morphogenesis), GO:0048870 (cell motility), GO:0042221 (response to chemical), GO:0090130 (tissue migration), GO:0007389 (pattern specification process), GO:0051301 (cell division), GO:0051241 (negative regulation of multicellular organismal process), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0032504 (multicellular organism reproduction), GO:0003006 (developmental process involved in reproduction), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0009791 (post-embryonic development), GO:0007267 (cell-cell signaling), GO:0050793 (regulation of developmental process), GO:0022412 (cellular process involved in reproduction in multicellular organism), GO:0048522 (positive regulation of cellular process), GO:0009607 (response to biotic stimulus), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0007165 (signal transduction), GO:0048869 (cellular developmental process), GO:0007275 (multicellular organism development), GO:0002682 (regulation of immune system process), GO:0006950 (response to stress), GO:0048609 (multicellular organismal reproductive process), GO:0007154 (cell communication), GO:0002165 (instar larval or pupal development), GO:0007552 (metamorphosis), GO:0048729 (tissue morphogenesis), GO:0043207 (response to external biotic stimulus), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0051961 (negative regulation of nervous system development), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0070848 (response to growth factor), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:0009617 (response to bacterium), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0048589 (developmental growth), GO:0009887 (animal organ morphogenesis), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0045595 (regulation of cell differentiation), GO:0009790 (embryo development), GO:0007166 (cell surface receptor signaling pathway), GO:0016043 (cellular component organization), GO:0009886 (post-embryonic animal morphogenesis), GO:0042246 (tissue regeneration), GO:0007297 (follicle cell of egg chamber migration), GO:0016477 (cell migration), GO:0007276 (gamete generation), GO:0048736 (appendage development), GO:0030707 (follicle cell of egg chamber development), GO:0007281 (germ cell development), GO:0009798 (axis specification), GO:0009611 (response to wounding), GO:0090132 (epithelium migration), GO:0006952 (defense response), GO:0090132 (epithelium migration), GO:1901700 (response to oxygen-containing compound), GO:0035107 (appendage morphogenesis), GO:0009880 (embryonic pattern specification), GO:0010033 (response to organic substance), GO:0098542 (defense response to other organism), GO:0045165 (cell fate commitment), GO:0001709 (cell fate determination), GO:2000026 (regulation of multicellular organismal development), GO:0048598 (embryonic morphogenesis), GO:0009888 (tissue development), GO:0003002 (regionalization), GO:0060322 (head development), GO:0045596 (negative regulation of cell differentiation), GO:0070887 (cellular response to chemical stimulus), GO:0045596 (negative regulation of cell differentiation), GO:0009617 (response to bacterium), GO:0009889 (regulation of biosynthetic process), GO:0031323 (regulation of cellular metabolic process), GO:0008354 (germ cell migration), GO:0080090 (regulation of primary metabolic process), GO:0010631 (epithelial cell migration), GO:0097305 (response to alcohol), GO:0060562 (epithelial tube morphogenesis), GO:0030030 (cell projection organization), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0036314 (response to sterol), GO:0048880 (sensory system development), GO:0048707 (instar larval or pupal morphogenesis), GO:0090596 (sensory organ morphogenesis), GO:0035114 (imaginal disc-derived appendage morphogenesis), GO:0002009 (morphogenesis of an epithelium), GO:0007298 (border follicle cell migration), GO:0010468 (regulation of gene expression), GO:0048666 (neuron development), GO:0007447 (imaginal disc pattern formation), GO:0050768 (negative regulation of neurogenesis), GO:0007399 (nervous system development), GO:0007292 (female gamete generation), GO:0002064 (epithelial cell development), GO:0048737 (imaginal disc-derived appendage development), GO:0045995 (regulation of embryonic development), GO:0008544 (epidermis development), GO:0009954 (proximal/distal pattern formation), GO:0072359 (circulatory system development), GO:0009953 (dorsal/ventral pattern formation), GO:0048563 (post-embryonic animal organ morphogenesis), GO:0007560 (imaginal disc morphogenesis), GO:0051252 (regulation of RNA metabolic process), GO:0007444 (imaginal disc development), GO:0048858 (cell projection morphogenesis), GO:1901701 (cellular response to oxygen-containing compound), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0007507 (heart development), GO:0071310 (cellular response to organic substance), GO:0035120 (post-embryonic appendage morphogenesis), GO:0060284 (regulation of cell development), GO:0007423 (sensory organ development), GO:0048477 (oogenesis), GO:0035114 (imaginal disc-derived appendage morphogenesis), GO:0051960 (regulation of nervous system development), GO:0001667 (ameboidal-type cell migration), GO:0007219 (Notch signaling pathway), GO:0030855 (epithelial cell differentiation), GO:0022008 (neurogenesis), GO:0042060 (wound healing), GO:0032870 (cellular response to hormone stimulus), GO:0098742 (cell-cell adhesion via plasma-membrane adhesion molecules), GO:0033993 (response to lipid), GO:0042742 (defense response to bacterium), GO:0048569 (post-embryonic animal organ development), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0072002 (Malpighian tubule development), GO:0060429 (epithelium development), GO:0051253 (negative regulation of RNA metabolic process), GO:0030182 (neuron differentiation), GO:0071363 (cellular response to growth factor stimulus), GO:0009952 (anterior/posterior pattern specification), GO:0009792 (embryo development ending in birth or egg hatching), GO:0060541 (respiratory system development), GO:0048592 (eye morphogenesis), GO:0046552 (photoreceptor cell fate commitment), GO:0007472 (wing disc morphogenesis), GO:2001141 (regulation of RNA biosynthetic process), GO:0120039 (plasma membrane bounded cell projection morphogenesis), GO:0007448 (anterior/posterior pattern specification, imaginal disc), GO:0150063 (visual system development), GO:0007424 (open tracheal system development), GO:0035220 (wing disc development), GO:0042461 (photoreceptor cell development), GO:0035315 (hair cell differentiation), GO:0050767 (regulation of neurogenesis), GO:0048699 (generation of neurons), GO:0007476 (imaginal disc-derived wing morphogenesis), GO:0007391 (dorsal closure), GO:0035222 (wing disc pattern formation), GO:0008360 (regulation of cell shape), GO:0048667 (cell morphogenesis involved in neuron differentiation), GO:0001654 (eye development), GO:0001700 (embryonic development via the syncytial blastoderm), GO:0046530 (photoreceptor cell differentiation), GO:0120036 (plasma membrane bounded cell projection organization), GO:0006355 (regulation of DNA-templated transcription), GO:0035220 (wing disc development), GO:0043704 (photoreceptor cell fate specification), GO:0031175 (neuron projection development), GO:0035218 (leg disc development), GO:0009913 (epidermal cell differentiation), GO:0010002 (cardioblast differentiation), GO:0048812 (neuron projection morphogenesis), GO:0071326 (cellular response to monosaccharide stimulus), GO:0061564 (axon development), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0048190 (wing disc dorsal/ventral pattern formation), GO:0007409 (axonogenesis), GO:0048749 (compound eye development)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0031974 (membrane-enclosed lumen), GO:0005829 (cytosol), GO:0071944 (cell periphery), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0005783 (endoplasmic reticulum), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)