| Post Translational Modifications | 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 TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane. Hydroxylated by HIF1AN. Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1. Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway. |
| 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 bone remodeling and homeostasis. In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. Positively regulates self-renewal of liver cancer cells. |
| Protein Name | Neurogenic Locus Notch Homolog Protein 2Notch 2Hn2 Cleaved Into - Notch 2 Extracellular TruncationN2ecd - Notch 2 Intracellular DomainN2icd |
| Database Links | Reactome: R-HSA-1912399Reactome: R-HSA-1912408Reactome: R-HSA-1912420Reactome: R-HSA-2197563Reactome: R-HSA-2979096Reactome: R-HSA-350054Reactome: R-HSA-5083630Reactome: R-HSA-9013695 |
| Cellular Localisation | Notch 2 Extracellular Truncation: Cell MembraneSingle-Pass Type I Membrane ProteinNotch 2 Intracellular Domain: NucleusCytoplasmFollowing Proteolytical Processing Nicd Is Translocated To The NucleusRetained At The Cytoplasm By Tcim |
| Alternative Protein Names | Neurogenic Locus Notch Homolog Protein 2 proteinNotch 2 proteinHn2 Cleaved Into - Notch 2 Extracellular Truncation proteinN2ecd - Notch 2 Intracellular Domain proteinN2icd proteinNOTCH2 protein |
Information sourced from Uniprot.org
