| IED ID | IndEnz0002008648 |
| Enzyme Type ID | protease008648 |
| Protein Name |
Neurogenic locus notch homolog protein 1 Notch 1 Cleaved into: Notch 1 extracellular truncation NEXT ; Notch 1 intracellular domain NICD |
| Gene Name | notch1a notch |
| Organism | Danio rerio (Zebrafish) (Brachydanio rerio) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Actinopterygii Actinopteri Neopterygii Teleostei Osteoglossocephalai Clupeocephala Otomorpha Ostariophysi Otophysi Cypriniphysae Cypriniformes (carps and others) Cyprinoidei Danionidae Danioninae Danio Danio rerio (Zebrafish) (Brachydanio rerio) |
| Enzyme Sequence | MNRFLVKLTLLTAASLATVAQGQRCSEYCQNGGICEYKPSGEASCRCPADFVGAQCQFPNPCNPSPCRNGGVCRPQMQGNEVGVKCDCVLGFSDRLCLTPVNHACMNSPCRNGGTCSLLTLDTFTCRCQPGWSGKTCQLADPCASNPCANGGQCSAFESHYICTCPPNFHGQTCRQDVNECAVSPSPCRNGGTCINEVGSYLCRCPPEYTGPHCQRLYQPCLPSPCRSGGTCVQTSDTTHTCSCLPGFTGQTCEHNVDDCTQHACENGGPCIDGINTYNCHCDKHWTGQYCTEDVDECELSPNACQNGGTCHNTIGGFHCVCVNGWTGDDCSENIDDCASAACSHGATCHDRVASFFCECPHGRTGLLCHLDDACISNPCQKGSNCDTNPVSGKAICTCPPGYTGSACNQDIDECSLGANPCEHGGRCLNTKGSFQCKCLQGYEGPRCEMDVNECKSNPCQNDATCLDQIGGFHCICMPGYEGVFCQINSDDCASQPCLNGKCIDKINSFHCECPKGFSGSLCQVDVDECASTPCKNGAKCTDGPNKYTCECTPGFSGIHCELDINECASSPCHYGVCRDGVASFTCDCRPGYTGRLCETNINECLSQPCRNGGTCQDRENAYICTCPKGTTGVNCEINIDDCKRKPCDYGKCIDKINGYECVCEPGYSGSMCNINIDDCALNPCHNGGTCIDGVNSFTCLCPDGFRDATCLSQHNECSSNPCIHGSCLDQINSYRCVCEAGWMGRNCDININECLSNPCVNGGTCKDMTSGYLCTCRAGFSGPNCQMNINECASNPCLNQGSCIDDVAGFKCNCMLPYTGEVCENVLAPCSPRPCKNGGVCRESEDFQSFSCNCPAGWQGQTCEVDINECVRNPCTNGGVCENLRGGFQCRCNPGFTGALCENDIDDCEPNPCSNGGVCQDRVNGFVCVCLAGFRGERCAEDIDECVSAPCRNGGNCTDCVNSYTCSCPAGFSGINCEINTPDCTESSCFNGGTCVDGISSFSCVCLPGFTGNYCQHDVNECDSRPCQNGGSCQDGYGTYKCTCPHGYTGLNCQSLVRWCDSSPCKNGGSCWQQGASFTCQCASGWTGIYCDVPSVSCEVAARQQGVSVAVLCRHAGQCVDAGNTHLCRCQAGYTGSYCQEQVDECQPNPCQNGATCTDYLGGYSCECVPGYHGMNCSKEINECLSQPCQNGGTCIDLVNTYKCSCPRGTQGVHCEIDIDDCSPSVDPLTGEPRCFNGGRCVDRVGGYGCVCPAGFVGERCEGDVNECLSDPCDPSGSYNCVQLINDFRCECRTGYTGKRCETVFNGCKDTPCKNGGTCAVASNTKHGYICKCQPGYSGSSCEYDSQSCGSLRCRNGATCVSGHLSPRCLCAPGFSGHECQTRMDSPCLVNPCYNGGTCQPISDAPFYRCSCPANFNGLLCHILDYSFSGGQGRDIAPPVEVEIRCEIAQCEGRGGNAICDTQCNNHACGWDGGDCSLNFDDPWQNCSAALQCWRYFNDGKCDEQCATAGCLYDGFDCQRLEGQCNPLYDQYCRDHYADGHCDQGCNNAECEWDGLDCADDVPQKLAVGSLVLVVHIPPDELRNRSSSFLRELSSLLHTNVVFRRDANGEALIFPYYGSEHELSKHKRSDWTDPGQLMQRARRSLTSFLKPRTRRELDHMEVKGSIVYLEIDNRQCFQQSDECFQSATDVAAFLGALASSGNLNVPYIIEAVTSEGGPPKTGEMYPMFLVLLALAVLALAAVGVVVSRKRKREHGQLWFPEGFKVNEPKKKRREPVGEDSVGLKPLKNSDSSLMDEQLSEWAEDDTNKRFRFEGQSILEMSGQLDHRQWTQQHLDAADLRLNSMAPTPPQGQIENDCMDVNVRGPDGFTPLMIASCSGGGLENENGEAEEDPSADVITDFIYHGANLHNQTDRTGETALHLAARYARSDAAKRLLESCADANVQDNMGRTPLHAAVAADAQGVFQILIRNRATDLDARMHDGTTPLILATRLAVEGMVEELINCHADPNAVDDSGKSALHWAAAVNNVDAAVVLLKNGANKDLQNNKEETPLFLAAREGSYETAKVLLDHLANRDIADHLDQLPRDIAHERMHHDIVRLLEEYNLVRSPPLPLSPPLCCPNTYLGIKPSPGNNNNTAKKTRKPGGKGVGGKDSGKDIRTKKKKSGDGKNGGIMEVGVLSPVDSLESPHGYLSDVSSPPMMTSPFQQSPPISLNQLQGLADSHMGGALQGLGKPFDSAPRLSHLPVANNVGGAQAGACDWLQRVQQQQQQQQQQQQAGMLMPTMLSATNMPQVMGYPTMQSSHLGAPSHMIAHQNMAPMQHQNISHHFLGDLSGLDLQSSSGHAPIQTILPQDSQRMAPPISSTQFLTPPSQHSYSNPMDNTPNHQQVPDHPFLTPSAGSPDQWSSSSPHSNLSDWSEGISSPPTSMQMNHIPEAFK |
| Enzyme Length | 2437 |
| Uniprot Accession Number | P46530 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis (By similarity). Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO) (By similarity). {ECO:0000250|UniProtKB:Q01705}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (3); Compositional bias (3); Disulfide bond (117); Domain (36); Glycosylation (8); Region (3); Repeat (9); Signal peptide (1); Site (2); Topological domain (2); Transmembrane (1) |
| Keywords | ANK repeat;Activator;Angiogenesis;Calcium;Cell membrane;Developmental protein;Differentiation;Disulfide bond;EGF-like domain;Glycoprotein;Membrane;Metal-binding;Notch signaling pathway;Nucleus;Receptor;Reference proteome;Repeat;Signal;Transcription;Transcription regulation;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q01705}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q01705}.; SUBCELLULAR LOCATION: [Notch 1 intracellular domain]: Nucleus {ECO:0000250|UniProtKB:Q01705}. Note=Following proteolytical processing NICD is translocated to the nucleus. {ECO:0000250|UniProtKB:Q01705}. |
| Modified Residue | |
| Post Translational Modification | PTM: Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by adam17 to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). Following endocytosis, this fragment is then cleaved by presenilin dependent gamma-secretase to release a Notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity). {ECO:0000250|UniProtKB:Q01705}.; PTM: O-glycosylated on the EGF-like domains. Contains both O-linked fucose and O-linked glucose. O-linked glycosylation by galnt11 is involved in determination of left/right symmetry: glycosylation promotes activation of notch1, possibly by promoting cleavage by adam17, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO) (By similarity). {ECO:0000250|UniProtKB:Q01705}. |
| Signal Peptide | SIGNAL 1..20; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11543616; 12954879; 14518000; 15042699; 15256591; 15280211; 15766754; 15809039; 15963491; 16225858; 16760970; 16876779; 17134690; 17199043; 17555741; 18627107; 18769591; 19056830; 19084503; 19553285; 20118921; 20637620; 20876649; 21060795; 21654806; 24598161; 24768892; 25230933; 25416946; 26994945; 29339404; 29628374; 31668618; 9007237; 9706695; |
| Motif | |
| Gene Encoded By | |
| Mass | 262,308 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |