Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:P46531 NOTCH1
| Class:Id | ReferenceGeneProduct:60520 |
|---|---|
| _chainChangeLog | signal peptide:1-18 added on Fri February 6 2015;chain:19-2555 added on Fri February 6 2015;chain:1721-2555 added on Fri February 6 2015;chain:1754-2555 added on Fri February 6 2015 |
| _displayName | UniProt:P46531 NOTCH1 |
| _timestamp | 2026-02-20 22:01:59 |
| chain | signal peptide:1-18 chain:19-2555 chain:1721-2555 chain:1754-2555 |
| checksum | E173C872D195F028 |
| comment | 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. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).SUBUNIT Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1 (PubMed:11101851, PubMed:12370315). The NOTCH1 intracellular domain interacts with SNW1; the interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ (PubMed:10713164). The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation (PubMed:17573339). Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A. Interacts (via NICD) with BCL6; the interaction decreases MAML1 recruitment by NOTCH1 NICD on target genes DNA and inhibits NOTCH1 transactivation activity. Interacts with THBS4 (By similarity). Interacts (via the EGF-like repeat region) with CCN3 (via CTCK domain) (PubMed:12050162). Interacts (via EGF-like domains) with DLL4 (via N-terminal DSL and MNNL domains) (By similarity). Interacts with ZMIZ1. Interacts (via NICD domain) with MEGF10 (via the cytoplasmic domain). Interacts with DLL1 and JAG1 (By similarity). Interacts (via NICD domain) with PRAG1 (By similarity). Forms a complex with PRAG1, N1ICD and MAML1, in a MAML1-dependent manner (By similarity). Interacts (via transmembrane region) with PSEN1; the interaction is direct (PubMed:30598546). Interacts with ZFP64 (By similarity).INTERACTION Non-activated receptor is targeted for lysosomal degradation via the endosomal pathway; transport from late endosomes to lysosomes requires deubiquitination by USP12.SUBCELLULAR LOCATION Following proteolytical processing NICD is translocated to the nucleus. Nuclear location may require MEGF10.TISSUE SPECIFICITY In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues.DOMAIN Interaction with PSEN1 causes partial unwinding of the transmembrane helix, facilitating access to the scissile peptide bond.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 (By similarity). 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) (PubMed:24226769). Following endocytosis, this fragment is then cleaved by one of the catalytic subunits of gamma-secretase (PSEN1 or PSEN2), to release a Notch-derived peptide containing the intracellular domain (NICD) from the membrane (PubMed:30598546).PTM Phosphorylated.PTM O-glycosylated on the EGF-like domains (PubMed:24226769). O-glucosylated at Ser-435 by KDELC1 and KDELC2 (PubMed:30127001). Contains both O-linked fucose and O-linked glucose in the EGF-like domains 11, 12 and 13, which are interacting with the residues on DLL4 (By similarity). 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) (PubMed:24226769). MFNG-, RFNG- and LFNG-mediated modification of O-fucose residues at specific EGF-like domains results in inhibition of its activation by JAG1 and enhancement of its activation by DLL1 via an increased binding to DLL1 (By similarity).PTM Ubiquitinated. Undergoes 'Lys-29'-linked polyubiquitination by ITCH; promotes the lysosomal degradation of non-activated internalized NOTCH1 (PubMed:18628966, PubMed:23886940). Deubiquitination by USP12 is required for transport of internalized non-activated receptor from late endosomes to lysosomes for degradation (PubMed:22778262). Monoubiquitination at Lys-1759 is required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it. Deubiquitination by EIF3F is necessary for nuclear import of activated Notch (PubMed:24226769).PTM Hydroxylated at Asn-1955 by HIF1AN. Hydroxylated at Asn-2022 by HIF1AN (By similarity). Hydroxylation reduces affinity for HI1AN and may thus indirectly modulate negative regulation of NICD (By similarity).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the NOTCH family. |
| description | recommendedName: Neurogenic locus notch homolog protein 1 shortName: Notch 1 shortName: hN1 alternativeName: Translocation-associated notch protein TAN-1 component recommendedName: Notch 1 extracellular truncation shortName: NEXT /component component recommendedName: Notch 1 intracellular domain shortName: NICD /component |
| geneName | NOTCH1 TAN1 |
| identifier | P46531 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Activator Angiogenesis ANK repeat Calcium Cell membrane Developmental protein Differentiation Direct protein sequencing Disease variant Disulfide bond EGF-like domain Endosome Glycoprotein Hydroxylation Isopeptide bond Membrane Metal-binding Notch signaling pathway Nucleus Phosphoprotein Proteomics identification Receptor Reference proteome Repeat Signal Transcription Transcription regulation Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | NOTCH1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:1606483] ENSEMBL:ENSG00000148400 NOTCH1 [Homo sapiens] |
| secondaryIdentifier | NOTC1_HUMAN Q59ED8 Q5SXM3 |
| sequenceLength | 2555 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:157024] Pre-NOTCH1 [endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:157092] NOTCH1(1665-2555) [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:157104] NOTCH1(19-2555) [Golgi lumen] [Homo sapiens] [EntityWithAccessionedSequence:157200] NEXT1 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:157239] NOTCH1(1665-2555) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:157634] NICD1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:157654] NOTCH1(1665-1720) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:157656] NOTCH1(1721-1753) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:157939] NICD1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:1467396] 17xFucT-2xFucS-NOTCH1(19-2555) [endoplasmic reticulum membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:1467296] O-glucosyl-L-serine at 534 [ModifiedResidue:1467302] O-glucosyl-L-serine at 496 [ModifiedResidue:1467303] O-fucosyl-L-threonine at 1197 [ModifiedResidue:1467309] O-fucosyl-L-threonine at 1402 [ModifiedResidue:1467314] O-fucosyl-L-threonine at 73 [ModifiedResidue:1467315] O-fucosyl-L-threonine at 194 [ModifiedResidue:1467322] O-fucosyl-L-threonine at 767 [ModifiedResidue:1467324] O-fucosyl-L-threonine at 1362 [ModifiedResidue:1467329] O-fucosyl-L-threonine at 1243 [ModifiedResidue:1467331] O-fucosyl-L-threonine at 997 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P46531 NOTCH1 (60520)
