UniProtKB - P46531 (NOTC1_HUMAN)
Neurogenic locus notch homolog protein 1
NOTCH1
Functioni
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).
1 PublicationSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 432 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 435 | Calcium 1; via amide nitrogenBy similarity | 1 | |
Metal bindingi | 452 | Calcium 2By similarity | 1 | |
Metal bindingi | 453 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 455 | Calcium 2By similarity | 1 | |
Metal bindingi | 469 | Calcium 2By similarity | 1 | |
Metal bindingi | 470 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 490 | Calcium 3By similarity | 1 | |
Metal bindingi | 491 | Calcium 3; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 493 | Calcium 3By similarity | 1 | |
Metal bindingi | 507 | Calcium 3By similarity | 1 | |
Metal bindingi | 508 | Calcium 3; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 1457 | Calcium 4; via carbonyl oxygen | 1 | |
Metal bindingi | 1460 | Calcium 4 | 1 | |
Metal bindingi | 1475 | Calcium 4 | 1 | |
Metal bindingi | 1478 | Calcium 4 | 1 |
GO - Molecular functioni
- calcium ion binding Source: InterPro
- chromatin DNA binding Source: Ensembl
- enzyme binding Source: UniProtKB
- enzyme inhibitor activity Source: UniProtKB
- identical protein binding Source: IntAct
- Notch binding Source: Ensembl
- transcription coactivator activity Source: BHF-UCL
- transmembrane signaling receptor activity Source: Ensembl
GO - Biological processi
- animal organ regeneration Source: Ensembl
- aortic valve morphogenesis Source: BHF-UCL
- apoptotic process involved in embryonic digit morphogenesis Source: Ensembl
- arterial endothelial cell differentiation Source: BHF-UCL
- astrocyte differentiation Source: Ensembl
- atrioventricular node development Source: Ensembl
- atrioventricular valve morphogenesis Source: BHF-UCL
- auditory receptor cell fate commitment Source: Ensembl
- axon guidance Source: GO_Central
- branching morphogenesis of an epithelial tube Source: Ensembl
- cardiac atrium morphogenesis Source: BHF-UCL
- cardiac chamber formation Source: BHF-UCL
- cardiac epithelial to mesenchymal transition Source: BHF-UCL
- cardiac left ventricle morphogenesis Source: BHF-UCL
- cardiac muscle cell proliferation Source: Ensembl
- cardiac muscle tissue morphogenesis Source: BHF-UCL
- cardiac right atrium morphogenesis Source: BHF-UCL
- cardiac right ventricle formation Source: Ensembl
- cardiac septum morphogenesis Source: BHF-UCL
- cardiac vascular smooth muscle cell development Source: BHF-UCL
- cardiac ventricle morphogenesis Source: BHF-UCL
- cell differentiation in spinal cord Source: Ensembl
- cell fate specification Source: Ensembl
- cell migration involved in endocardial cushion formation Source: BHF-UCL
- cellular response to follicle-stimulating hormone stimulus Source: BHF-UCL
- cellular response to tumor cell Source: UniProtKB
- cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
- cilium assembly Source: UniProtKB
- collecting duct development Source: Ensembl
- compartment pattern specification Source: Ensembl
- coronary artery morphogenesis Source: BHF-UCL
- coronary sinus valve morphogenesis Source: Ensembl
- coronary vein morphogenesis Source: BHF-UCL
- determination of left/right symmetry Source: BHF-UCL
- distal tubule development Source: Ensembl
- embryonic hindlimb morphogenesis Source: Ensembl
- endocardial cell differentiation Source: BHF-UCL
- endocardial cushion morphogenesis Source: BHF-UCL
- endocardium development Source: BHF-UCL
- endocardium morphogenesis Source: BHF-UCL
- endoderm development Source: Ensembl
- epithelial to mesenchymal transition Source: BHF-UCL
- epithelial to mesenchymal transition involved in endocardial cushion formation Source: BHF-UCL
- forebrain development Source: Ensembl
- foregut morphogenesis Source: Ensembl
- gene expression Source: Ensembl
- glomerular mesangial cell development Source: Ensembl
- growth involved in heart morphogenesis Source: BHF-UCL
- hair follicle morphogenesis Source: Ensembl
- heart development Source: DFLAT
- heart looping Source: BHF-UCL
- heart trabecula morphogenesis Source: BHF-UCL
- homeostasis of number of cells within a tissue Source: BHF-UCL
- humoral immune response Source: Ensembl
- immune response Source: UniProtKB
- inflammatory response to antigenic stimulus Source: Ensembl
- interleukin-17-mediated signaling pathway Source: Ensembl
- in utero embryonic development Source: Ensembl
- keratinocyte differentiation Source: Ensembl
- left/right axis specification Source: Ensembl
- liver development Source: Ensembl
- lung development Source: Ensembl
- mesenchymal cell development Source: BHF-UCL
- mitral valve formation Source: BHF-UCL
- negative regulation of anoikis Source: BHF-UCL
- negative regulation of biomineral tissue development Source: BHF-UCL
- negative regulation of BMP signaling pathway Source: BHF-UCL
- negative regulation of calcium ion-dependent exocytosis Source: Ensembl
- negative regulation of canonical Wnt signaling pathway Source: Ensembl
- negative regulation of cardiac muscle hypertrophy Source: BHF-UCL
- negative regulation of catalytic activity Source: UniProtKB
- negative regulation of cell adhesion molecule production Source: ARUK-UCL
- negative regulation of cell-cell adhesion mediated by cadherin Source: ARUK-UCL
- negative regulation of cell migration involved in sprouting angiogenesis Source: UniProtKB
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of cell proliferation involved in heart valve morphogenesis Source: BHF-UCL
- negative regulation of cell-substrate adhesion Source: BHF-UCL
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- negative regulation of endothelial cell chemotaxis Source: UniProtKB
- negative regulation of extracellular matrix constituent secretion Source: BHF-UCL
- negative regulation of gene expression Source: UniProtKB
- negative regulation of glial cell proliferation Source: UniProtKB
- negative regulation of inner ear auditory receptor cell differentiation Source: Ensembl
- negative regulation of myoblast differentiation Source: UniProtKB
- negative regulation of myotube differentiation Source: UniProtKB
- negative regulation of neurogenesis Source: UniProtKB
- negative regulation of oligodendrocyte differentiation Source: UniProtKB
- negative regulation of ossification Source: BHF-UCL
- negative regulation of osteoblast differentiation Source: BHF-UCL
- negative regulation of photoreceptor cell differentiation Source: Ensembl
- negative regulation of pro-B cell differentiation Source: UniProtKB
- negative regulation of stem cell differentiation Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: BHF-UCL
- negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
- neural tube development Source: Ensembl
- neuronal stem cell population maintenance Source: UniProtKB
- Notch signaling involved in heart development Source: BHF-UCL
- Notch signaling pathway Source: UniProtKB
- Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation Source: Ensembl
- oligodendrocyte differentiation Source: Ensembl
- outflow tract morphogenesis Source: BHF-UCL
- pericardium morphogenesis Source: BHF-UCL
- positive regulation of aorta morphogenesis Source: Ensembl
- positive regulation of apoptotic process involved in morphogenesis Source: BHF-UCL
- positive regulation of astrocyte differentiation Source: UniProtKB
- positive regulation of BMP signaling pathway Source: UniProtKB
- positive regulation of cardiac epithelial to mesenchymal transition Source: BHF-UCL
- positive regulation of cardiac muscle cell proliferation Source: BHF-UCL
- positive regulation of cell migration Source: BHF-UCL
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of endothelial cell differentiation Source: Ensembl
- positive regulation of epithelial cell proliferation Source: Ensembl
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of gene expression Source: BHF-UCL
- positive regulation of keratinocyte differentiation Source: Ensembl
- positive regulation of neuroblast proliferation Source: Ensembl
- positive regulation of Notch signaling pathway Source: Ensembl
- positive regulation of Ras protein signal transduction Source: UniProtKB
- positive regulation of receptor signaling pathway via JAK-STAT Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
- positive regulation of transcription of Notch receptor target Source: BHF-UCL
- positive regulation of viral genome replication Source: Ensembl
- prostate gland epithelium morphogenesis Source: Ensembl
- protein catabolic process Source: Ensembl
- protein import into nucleus Source: Ensembl
- pulmonary valve morphogenesis Source: BHF-UCL
- regulation of epithelial cell proliferation involved in prostate gland development Source: Ensembl
- regulation of extracellular matrix assembly Source: BHF-UCL
- regulation of somitogenesis Source: Ensembl
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation Source: BHF-UCL
- response to corticosteroid Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- response to muramyl dipeptide Source: Ensembl
- secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development Source: Ensembl
- skeletal muscle cell differentiation Source: Ensembl
- somatic stem cell division Source: Ensembl
- spermatogenesis Source: Ensembl
- sprouting angiogenesis Source: Ensembl
- T-helper 17 type immune response Source: Ensembl
- tissue regeneration Source: Ensembl
- tube formation Source: UniProtKB
- vasculogenesis involved in coronary vascular morphogenesis Source: BHF-UCL
- venous endothelial cell differentiation Source: BHF-UCL
- ventricular septum morphogenesis Source: BHF-UCL
- ventricular trabecula myocardium morphogenesis Source: BHF-UCL
Keywordsi
Molecular function | Activator, Developmental protein, Receptor |
Biological process | Angiogenesis, Differentiation, Notch signaling pathway, Transcription, Transcription regulation |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | P46531 |
Reactomei | R-HSA-1912399, Pre-NOTCH Processing in the Endoplasmic Reticulum R-HSA-1912408, Pre-NOTCH Transcription and Translation R-HSA-1912420, Pre-NOTCH Processing in Golgi R-HSA-210744, Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells R-HSA-2122947, NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-2644606, Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2644607, Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling R-HSA-2660826, Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant R-HSA-2691232, Constitutive Signaling by NOTCH1 HD Domain Mutants R-HSA-2894862, Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-350054, Notch-HLH transcription pathway R-HSA-5083630, Defective LFNG causes SCDO3 R-HSA-8941856, RUNX3 regulates NOTCH signaling R-HSA-9013508, NOTCH3 Intracellular Domain Regulates Transcription R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription |
SignaLinki | P46531 |
SIGNORi | P46531 |
Protein family/group databases
TCDBi | 9.B.87.1.12, the selenoprotein p receptor (selp-receptor) family |
Names & Taxonomyi
Protein namesi | Recommended name: Neurogenic locus notch homolog protein 1Short name: Notch 1 Short name: hN1 Alternative name(s): Translocation-associated notch protein TAN-1 Cleaved into the following 2 chains: |
Gene namesi | Name:NOTCH1 Synonyms:TAN1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7881, NOTCH1 |
MIMi | 190198, gene |
neXtProti | NX_P46531 |
VEuPathDBi | HostDB:ENSG00000148400 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein 1 Publication
Nucleus
- Nucleus By similarity
Note: Following proteolytical processing NICD is translocated to the nucleus. Nuclear location may require MEGF10.By similarity
Cytosol
- cytosol Source: Reactome
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: Reactome
Extracellular region or secreted
- extracellular region Source: Reactome
Golgi apparatus
- Golgi membrane Source: Reactome
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- plasma membrane Source: BHF-UCL
Other locations
- acrosomal vesicle Source: Ensembl
- adherens junction Source: UniProtKB
- cell surface Source: GO_Central
- integral component of membrane Source: UniProtKB-KW
- MAML1-RBP-Jkappa- ICN1 complex Source: UniProtKB
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 19 – 1735 | Extracellular2 PublicationsAdd BLAST | 1717 | |
Transmembranei | 1736 – 1756 | Helical2 PublicationsAdd BLAST | 21 | |
Topological domaini | 1757 – 2555 | Cytoplasmic2 PublicationsAdd BLAST | 799 |
Keywords - Cellular componenti
Cell membrane, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Aortic valve disease 1 (AOVD1)1 Publication
Adams-Oliver syndrome 5 (AOS5)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071960 | 429 | C → R in AOS5. 1 PublicationCorresponds to variant dbSNP:rs587777736EnsemblClinVar. | 1 | |
Natural variantiVAR_071961 | 1496 | C → Y in AOS5. 1 PublicationCorresponds to variant dbSNP:rs587781259EnsemblClinVar. | 1 | |
Natural variantiVAR_071962 | 1989 | D → N in AOS5. 1 PublicationCorresponds to variant dbSNP:rs587777734EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1728 | P → C: Formation of an artifactual disulfide bond with PSEN1. 1 Publication | 1 | |
Mutagenesisi | 1755 – 1761 | Missing : Loss of proteolytic cleavage by gamma-secretase. 1 Publication | 7 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 4851 |
GeneReviewsi | NOTCH1 |
MalaCardsi | NOTCH1 |
MIMi | 109730, phenotype 616028, phenotype |
OpenTargetsi | ENSG00000148400 |
Orphaneti | 974, Adams-Oliver syndrome 402075, Familial bicuspid aortic valve |
PharmGKBi | PA31683 |
Miscellaneous databases
Pharosi | P46531, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2146346 |
GuidetoPHARMACOLOGYi | 2861 |
Genetic variation databases
BioMutai | NOTCH1 |
DMDMi | 206729936 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | Sequence analysisAdd BLAST | 18 | |
ChainiPRO_0000007674 | 19 – 2555 | Neurogenic locus notch homolog protein 1Add BLAST | 2537 | |
ChainiPRO_0000007675 | 1721 – 2555 | Notch 1 extracellular truncationBy similarityAdd BLAST | 835 | |
ChainiPRO_0000007676 | 1754 – 2555 | Notch 1 intracellular domainBy similarityAdd BLAST | 802 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 24 ↔ 37 | PROSITE-ProRule annotation | ||
Disulfide bondi | 31 ↔ 46 | PROSITE-ProRule annotation | ||
Glycosylationi | 41 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 48 ↔ 57 | PROSITE-ProRule annotation | ||
Disulfide bondi | 63 ↔ 74 | PROSITE-ProRule annotation | ||
Glycosylationi | 65 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 68 ↔ 87 | PROSITE-ProRule annotation | ||
Glycosylationi | 73 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 89 ↔ 98 | PROSITE-ProRule annotation | ||
Disulfide bondi | 106 ↔ 117 | PROSITE-ProRule annotation | ||
Disulfide bondi | 111 ↔ 127 | PROSITE-ProRule annotation | ||
Glycosylationi | 116 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 129 ↔ 138 | PROSITE-ProRule annotation | ||
Disulfide bondi | 144 ↔ 155 | PROSITE-ProRule annotation | ||
Glycosylationi | 146 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 149 ↔ 164 | PROSITE-ProRule annotation | ||
Disulfide bondi | 166 ↔ 175 | PROSITE-ProRule annotation | ||
Disulfide bondi | 182 ↔ 195 | PROSITE-ProRule annotation | ||
Disulfide bondi | 189 ↔ 204 | PROSITE-ProRule annotation | ||
Glycosylationi | 194 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 206 ↔ 215 | PROSITE-ProRule annotation | ||
Disulfide bondi | 222 ↔ 233 | PROSITE-ProRule annotation | ||
Disulfide bondi | 227 ↔ 243 | PROSITE-ProRule annotation | ||
Glycosylationi | 232 | O-linked (Fuc...) threonine; alternate1 Publication | 1 | |
Glycosylationi | 232 | O-linked (GalNAc...) threonine; alternate1 Publication | 1 | |
Disulfide bondi | 245 ↔ 254 | PROSITE-ProRule annotation | ||
Disulfide bondi | 261 ↔ 272 | PROSITE-ProRule annotation | ||
Disulfide bondi | 266 ↔ 281 | PROSITE-ProRule annotation | ||
Disulfide bondi | 283 ↔ 292 | PROSITE-ProRule annotation | ||
Disulfide bondi | 299 ↔ 312 | PROSITE-ProRule annotation | ||
Disulfide bondi | 306 ↔ 321 | PROSITE-ProRule annotation | ||
Glycosylationi | 311 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 323 ↔ 332 | PROSITE-ProRule annotation | ||
Disulfide bondi | 339 ↔ 350 | PROSITE-ProRule annotation | ||
Glycosylationi | 341 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 344 ↔ 359 | PROSITE-ProRule annotation | ||
Glycosylationi | 349 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 361 ↔ 370 | PROSITE-ProRule annotation | ||
Disulfide bondi | 376 ↔ 387 | PROSITE-ProRule annotation | ||
Glycosylationi | 378 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 381 ↔ 398 | PROSITE-ProRule annotation | ||
Disulfide bondi | 400 ↔ 409 | PROSITE-ProRule annotation | ||
Disulfide bondi | 416 ↔ 429 | By similarity | ||
Disulfide bondi | 423 ↔ 438 | By similarity | ||
Glycosylationi | 435 | O-linked (Glc...) serine1 Publication | 1 | |
Disulfide bondi | 440 ↔ 449 | By similarity | ||
Disulfide bondi | 456 ↔ 467 | By similarity | ||
Glycosylationi | 458 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 461 ↔ 476 | By similarity | ||
Glycosylationi | 466 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 478 ↔ 487 | By similarity | ||
Disulfide bondi | 494 ↔ 505 | By similarity | ||
Glycosylationi | 496 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 499 ↔ 514 | By similarity | ||
Disulfide bondi | 516 ↔ 525 | By similarity | ||
Disulfide bondi | 532 ↔ 543 | PROSITE-ProRule annotation | ||
Glycosylationi | 534 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 537 ↔ 552 | PROSITE-ProRule annotation | ||
Disulfide bondi | 554 ↔ 563 | PROSITE-ProRule annotation | ||
Disulfide bondi | 570 ↔ 580 | PROSITE-ProRule annotation | ||
Disulfide bondi | 575 ↔ 589 | PROSITE-ProRule annotation | ||
Disulfide bondi | 591 ↔ 600 | PROSITE-ProRule annotation | ||
Disulfide bondi | 607 ↔ 618 | PROSITE-ProRule annotation | ||
Glycosylationi | 609 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 612 ↔ 627 | PROSITE-ProRule annotation | ||
Glycosylationi | 617 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 629 ↔ 638 | PROSITE-ProRule annotation | ||
Disulfide bondi | 645 ↔ 655 | PROSITE-ProRule annotation | ||
Glycosylationi | 647 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 650 ↔ 664 | PROSITE-ProRule annotation | ||
Disulfide bondi | 666 ↔ 675 | PROSITE-ProRule annotation | ||
Disulfide bondi | 682 ↔ 693 | PROSITE-ProRule annotation | ||
Disulfide bondi | 687 ↔ 702 | PROSITE-ProRule annotation | ||
Glycosylationi | 692 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 704 ↔ 713 | PROSITE-ProRule annotation | ||
Disulfide bondi | 720 ↔ 730 | PROSITE-ProRule annotation | ||
Glycosylationi | 722 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 725 ↔ 739 | PROSITE-ProRule annotation | ||
Disulfide bondi | 741 ↔ 750 | PROSITE-ProRule annotation | ||
Disulfide bondi | 757 ↔ 768 | PROSITE-ProRule annotation | ||
Glycosylationi | 759 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 762 ↔ 777 | PROSITE-ProRule annotation | ||
Glycosylationi | 767 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 779 ↔ 788 | PROSITE-ProRule annotation | ||
Glycosylationi | 784 | O-linked (GlcNAc) serineBy similarity | 1 | |
Disulfide bondi | 795 ↔ 806 | PROSITE-ProRule annotation | ||
Glycosylationi | 797 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 800 ↔ 815 | PROSITE-ProRule annotation | ||
Glycosylationi | 805 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 817 ↔ 826 | PROSITE-ProRule annotation | ||
Disulfide bondi | 833 ↔ 844 | PROSITE-ProRule annotation | ||
Disulfide bondi | 838 ↔ 855 | PROSITE-ProRule annotation | ||
Disulfide bondi | 857 ↔ 866 | PROSITE-ProRule annotation | ||
Disulfide bondi | 873 ↔ 884 | PROSITE-ProRule annotation | ||
Disulfide bondi | 878 ↔ 893 | PROSITE-ProRule annotation | ||
Disulfide bondi | 895 ↔ 904 | PROSITE-ProRule annotation | ||
Disulfide bondi | 911 ↔ 922 | PROSITE-ProRule annotation | ||
Disulfide bondi | 916 ↔ 931 | PROSITE-ProRule annotation | ||
Glycosylationi | 921 | O-linked (Fuc) serineBy similarity | 1 | |
Disulfide bondi | 933 ↔ 942 | PROSITE-ProRule annotation | ||
Disulfide bondi | 949 ↔ 960 | PROSITE-ProRule annotation | ||
Glycosylationi | 951 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 954 ↔ 969 | PROSITE-ProRule annotation | ||
Glycosylationi | 959 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 971 ↔ 980 | PROSITE-ProRule annotation | ||
Disulfide bondi | 987 ↔ 998 | PROSITE-ProRule annotation | ||
Disulfide bondi | 992 ↔ 1007 | PROSITE-ProRule annotation | ||
Glycosylationi | 997 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 1009 ↔ 1018 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1025 ↔ 1036 | PROSITE-ProRule annotation | ||
Glycosylationi | 1027 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 1030 ↔ 1045 | PROSITE-ProRule annotation | ||
Glycosylationi | 1035 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 1047 ↔ 1056 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1063 ↔ 1074 | PROSITE-ProRule annotation | ||
Glycosylationi | 1065 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 1068 ↔ 1083 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1085 ↔ 1094 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1101 ↔ 1122 | Curated | ||
Disulfide bondi | 1116 ↔ 1131 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1133 ↔ 1142 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1149 ↔ 1160 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1154 ↔ 1169 | PROSITE-ProRule annotation | ||
Glycosylationi | 1159 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 1171 ↔ 1180 | PROSITE-ProRule annotation | ||
Glycosylationi | 1179 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1187 ↔ 1198 | PROSITE-ProRule annotation | ||
Glycosylationi | 1189 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 1192 ↔ 1207 | PROSITE-ProRule annotation | ||
Glycosylationi | 1197 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 1209 ↔ 1218 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1238 ↔ 1253 | PROSITE-ProRule annotation | ||
Glycosylationi | 1241 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1255 ↔ 1264 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1271 ↔ 1284 | PROSITE-ProRule annotation | ||
Glycosylationi | 1273 | O-linked (Glc...) serineBy similarity | 1 | |
Disulfide bondi | 1276 ↔ 1293 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1295 ↔ 1304 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1311 ↔ 1322 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1316 ↔ 1334 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1336 ↔ 1345 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1352 ↔ 1363 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1357 ↔ 1372 | PROSITE-ProRule annotation | ||
Glycosylationi | 1362 | O-linked (Fuc...) threonineBy similarity | 1 | |
Disulfide bondi | 1374 ↔ 1383 | PROSITE-ProRule annotation | ||
Glycosylationi | 1379 | O-linked (GlcNAc...) threonineBy similarity | 1 | |
Disulfide bondi | 1391 ↔ 1403 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1397 ↔ 1414 | PROSITE-ProRule annotation | ||
Glycosylationi | 1402 | O-linked (Fuc...) threonine; alternate1 Publication | 1 | |
Glycosylationi | 1402 | O-linked (GalNAc...) threonine; alternate1 Publication | 1 | |
Disulfide bondi | 1416 ↔ 1425 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1449 ↔ 1472 | 1 Publication | ||
Disulfide bondi | 1454 ↔ 1467 | 1 Publication | ||
Disulfide bondi | 1463 ↔ 1479 | 1 Publication | ||
Glycosylationi | 1489 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1490 ↔ 1514 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1496 ↔ 1509 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1505 ↔ 1521 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1536 ↔ 1549 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1545 ↔ 1561 | PROSITE-ProRule annotation | ||
Glycosylationi | 1587 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1725 | O-linked (GalNAc...) threonine1 Publication | 1 | |
Cross-linki | 1759 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 1861 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 1955 | (3S)-3-hydroxyasparagine; by HIF1AN; partial1 Publication | 1 | |
Modified residuei | 2022 | (3S)-3-hydroxyasparagine; by HIF1ANBy similarity | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 1664 – 1665 | Cleavage; by furin-like proteaseBy similarity | 2 | |
Sitei | 1710 – 1711 | Cleavage; by ADAM17By similarity | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, Hydroxylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P46531 |
jPOSTi | P46531 |
MassIVEi | P46531 |
MaxQBi | P46531 |
PaxDbi | P46531 |
PeptideAtlasi | P46531 |
PRIDEi | P46531 |
ProteomicsDBi | 55742 |
PTM databases
GlyGeni | P46531, 54 sites, 2 O-linked glycans (9 sites) |
iPTMneti | P46531 |
PhosphoSitePlusi | P46531 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000148400, Expressed in ventricular zone and 229 other tissues |
Genevisiblei | P46531, HS |
Organism-specific databases
HPAi | ENSG00000148400, Low tissue specificity |
Interactioni
Subunit structurei
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 transcractivation 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).
By similarity8 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 469 | Interaction with DLL4By similarity | 1 |
Binary interactionsi
P46531
Notch 1 intracellular domain (PRO_0000007676)
With | #Exp. | IntAct |
---|---|---|
MAML2 [Q8IZL2] | 2 | EBI-9692333,EBI-2864946 |
MAML3 [Q96JK9] | 2 | EBI-9692333,EBI-1043855 |
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- identical protein binding Source: IntAct
- Notch binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 110913, 302 interactors |
CORUMi | P46531 |
DIPi | DIP-29919N |
IntActi | P46531, 181 interactors |
MINTi | P46531 |
STRINGi | 9606.ENSP00000277541 |
Chemistry databases
BindingDBi | P46531 |
Miscellaneous databases
RNActi | P46531, protein |
Structurei
Secondary structure
3D structure databases
SASBDBi | P46531 |
SMRi | P46531 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P46531 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 20 – 58 | EGF-like 1PROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 59 – 99 | EGF-like 2PROSITE-ProRule annotationAdd BLAST | 41 | |
Domaini | 102 – 139 | EGF-like 3PROSITE-ProRule annotationAdd BLAST | 38 | |
Domaini | 140 – 176 | EGF-like 4PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 178 – 216 | EGF-like 5; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 218 – 255 | EGF-like 6PROSITE-ProRule annotationAdd BLAST | 38 | |
Domaini | 257 – 293 | EGF-like 7; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 295 – 333 | EGF-like 8; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 335 – 371 | EGF-like 9; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 372 – 410 | EGF-like 10PROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 412 – 450 | EGF-like 11; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 452 – 488 | EGF-like 12; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 490 – 526 | EGF-like 13; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 528 – 564 | EGF-like 14; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 566 – 601 | EGF-like 15; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 603 – 639 | EGF-like 16; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 641 – 676 | EGF-like 17; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 678 – 714 | EGF-like 18; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 716 – 751 | EGF-like 19; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 753 – 789 | EGF-like 20PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 791 – 827 | EGF-like 21; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 829 – 867 | EGF-like 22PROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 869 – 905 | EGF-like 23; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 907 – 943 | EGF-like 24PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 945 – 981 | EGF-like 25; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 983 – 1019 | EGF-like 26PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 1021 – 1057 | EGF-like 27PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 1059 – 1095 | EGF-like 28PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 1097 – 1143 | EGF-like 29CuratedAdd BLAST | 47 | |
Domaini | 1145 – 1181 | EGF-like 30PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 1183 – 1219 | EGF-like 31; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 1221 – 1265 | EGF-like 32; calcium-bindingPROSITE-ProRule annotationAdd BLAST | 45 | |
Domaini | 1267 – 1305 | EGF-like 33PROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 1307 – 1346 | EGF-like 34PROSITE-ProRule annotationAdd BLAST | 40 | |
Domaini | 1348 – 1384 | EGF-like 35PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 1387 – 1426 | EGF-like 36PROSITE-ProRule annotationAdd BLAST | 40 | |
Repeati | 1449 – 1489 | LNR 1PROSITE-ProRule annotationAdd BLAST | 41 | |
Repeati | 1490 – 1531 | LNR 2PROSITE-ProRule annotationAdd BLAST | 42 | |
Repeati | 1532 – 1571 | LNR 3PROSITE-ProRule annotationAdd BLAST | 40 | |
Repeati | 1927 – 1956 | ANK 1Sequence analysisAdd BLAST | 30 | |
Repeati | 1960 – 1990 | ANK 2Sequence analysisAdd BLAST | 31 | |
Repeati | 1994 – 2023 | ANK 3Sequence analysisAdd BLAST | 30 | |
Repeati | 2027 – 2056 | ANK 4Sequence analysisAdd BLAST | 30 | |
Repeati | 2060 – 2089 | ANK 5Sequence analysisAdd BLAST | 30 | |
Repeati | 2095 – 2122 | ANK 6Add BLAST | 28 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 420 – 421 | Interaction with DLL4By similarity | 2 | |
Regioni | 448 – 452 | Interaction with DLL4By similarity | 5 | |
Regioni | 1728 – 1760 | Interaction with PSEN11 PublicationAdd BLAST | 33 | |
Regioni | 1780 – 1808 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 1947 – 1955 | HIF1AN-bindingBy similarity | 9 | |
Regioni | 2014 – 2022 | HIF1AN-bindingBy similarity | 9 | |
Regioni | 2151 – 2194 | DisorderedSequence analysisAdd BLAST | 44 | |
Regioni | 2379 – 2447 | DisorderedSequence analysisAdd BLAST | 69 | |
Regioni | 2483 – 2555 | DisorderedSequence analysisAdd BLAST | 73 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 2170 – 2187 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 2379 – 2405 | Polar residuesSequence analysisAdd BLAST | 27 | |
Compositional biasi | 2483 – 2506 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 2514 – 2548 | Polar residuesSequence analysisAdd BLAST | 35 |
Domaini
Sequence similaritiesi
Keywords - Domaini
ANK repeat, EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1217, Eukaryota |
GeneTreei | ENSGT00940000157157 |
HOGENOMi | CLU_000576_2_0_1 |
InParanoidi | P46531 |
OMAi | NEGSCLD |
OrthoDBi | 7525at2759 |
PhylomeDBi | P46531 |
TreeFami | TF351641 |
Family and domain databases
DisProti | DP01104 |
Gene3Di | 1.25.40.20, 1 hit |
IDEALi | IID00199 |
InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR036770, Ankyrin_rpt-contain_sf IPR001881, EGF-like_Ca-bd_dom IPR013032, EGF-like_CS IPR000742, EGF-like_dom IPR000152, EGF-type_Asp/Asn_hydroxyl_site IPR018097, EGF_Ca-bd_CS IPR009030, Growth_fac_rcpt_cys_sf IPR008297, Notch IPR035993, Notch-like_dom_sf IPR022362, Notch_1 IPR024600, Notch_C IPR000800, Notch_dom IPR010660, Notch_NOD_dom IPR011656, Notch_NODP_dom |
Pfami | View protein in Pfam PF12796, Ank_2, 2 hits PF00008, EGF, 25 hits PF07645, EGF_CA, 4 hits PF12661, hEGF, 2 hits PF06816, NOD, 1 hit PF07684, NODP, 1 hit PF00066, Notch, 3 hits |
PIRSFi | PIRSF002279, Notch, 1 hit |
PRINTSi | PR01452, LNOTCHREPEAT PR01984, NOTCH1 |
SMARTi | View protein in SMART SM00248, ANK, 6 hits SM01334, DUF3454, 1 hit SM00181, EGF, 36 hits SM00179, EGF_CA, 33 hits SM00004, NL, 3 hits SM01338, NOD, 1 hit SM01339, NODP, 1 hit |
SUPFAMi | SSF48403, SSF48403, 1 hit SSF57184, SSF57184, 6 hits SSF90193, SSF90193, 3 hits |
PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit PS50088, ANK_REPEAT, 4 hits PS00010, ASX_HYDROXYL, 22 hits PS00022, EGF_1, 35 hits PS01186, EGF_2, 27 hits PS50026, EGF_3, 36 hits PS01187, EGF_CA, 20 hits PS50258, LNR, 3 hits |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MPPLLAPLLC LALLPALAAR GPRCSQPGET CLNGGKCEAA NGTEACVCGG
60 70 80 90 100
AFVGPRCQDP NPCLSTPCKN AGTCHVVDRR GVADYACSCA LGFSGPLCLT
110 120 130 140 150
PLDNACLTNP CRNGGTCDLL TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA
160 170 180 190 200
NGGQCLPFEA SYICHCPPSF HGPTCRQDVN ECGQKPGLCR HGGTCHNEVG
210 220 230 240 250
SYRCVCRATH TGPNCERPYV PCSPSPCQNG GTCRPTGDVT HECACLPGFT
260 270 280 290 300
GQNCEENIDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ
310 320 330 340 350
LMPNACQNGG TCHNTHGGYN CVCVNGWTGE DCSENIDDCA SAACFHGATC
360 370 380 390 400
HDRVASFYCE CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC
410 420 430 440 450
PSGYTGPACS QDVDECSLGA NPCEHAGKCI NTLGSFECQC LQGYTGPRCE
460 470 480 490 500
IDVNECVSNP CQNDATCLDQ IGEFQCICMP GYEGVHCEVN TDECASSPCL
510 520 530 540 550
HNGRCLDKIN EFQCECPTGF TGHLCQYDVD ECASTPCKNG AKCLDGPNTY
560 570 580 590 600
TCVCTEGYTG THCEVDIDEC DPDPCHYGSC KDGVATFTCL CRPGYTGHHC
610 620 630 640 650
ETNINECSSQ PCRHGGTCQD RDNAYLCFCL KGTTGPNCEI NLDDCASSPC
660 670 680 690 700
DSGTCLDKID GYECACEPGY TGSMCNINID ECAGNPCHNG GTCEDGINGF
710 720 730 740 750
TCRCPEGYHD PTCLSEVNEC NSNPCVHGAC RDSLNGYKCD CDPGWSGTNC
760 770 780 790 800
DINNNECESN PCVNGGTCKD MTSGYVCTCR EGFSGPNCQT NINECASNPC
810 820 830 840 850
LNQGTCIDDV AGYKCNCLLP YTGATCEVVL APCAPSPCRN GGECRQSEDY
860 870 880 890 900
ESFSCVCPTG WQGQTCEVDI NECVLSPCRH GASCQNTHGG YRCHCQAGYS
910 920 930 940 950
GRNCETDIDD CRPNPCHNGG SCTDGINTAF CDCLPGFRGT FCEEDINECA
960 970 980 990 1000
SDPCRNGANC TDCVDSYTCT CPAGFSGIHC ENNTPDCTES SCFNGGTCVD
1010 1020 1030 1040 1050
GINSFTCLCP PGFTGSYCQH DVNECDSQPC LHGGTCQDGC GSYRCTCPQG
1060 1070 1080 1090 1100
YTGPNCQNLV HWCDSSPCKN GGKCWQTHTQ YRCECPSGWT GLYCDVPSVS
1110 1120 1130 1140 1150
CEVAAQRQGV DVARLCQHGG LCVDAGNTHH CRCQAGYTGS YCEDLVDECS
1160 1170 1180 1190 1200
PSPCQNGATC TDYLGGYSCK CVAGYHGVNC SEEIDECLSH PCQNGGTCLD
1210 1220 1230 1240 1250
LPNTYKCSCP RGTQGVHCEI NVDDCNPPVD PVSRSPKCFN NGTCVDQVGG
1260 1270 1280 1290 1300
YSCTCPPGFV GERCEGDVNE CLSNPCDARG TQNCVQRVND FHCECRAGHT
1310 1320 1330 1340 1350
GRRCESVING CKGKPCKNGG TCAVASNTAR GFICKCPAGF EGATCENDAR
1360 1370 1380 1390 1400
TCGSLRCLNG GTCISGPRSP TCLCLGPFTG PECQFPASSP CLGGNPCYNQ
1410 1420 1430 1440 1450
GTCEPTSESP FYRCLCPAKF NGLLCHILDY SFGGGAGRDI PPPLIEEACE
1460 1470 1480 1490 1500
LPECQEDAGN KVCSLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF
1510 1520 1530 1540 1550
SDGHCDSQCN SAGCLFDGFD CQRAEGQCNP LYDQYCKDHF SDGHCDQGCN
1560 1570 1580 1590 1600
SAECEWDGLD CAEHVPERLA AGTLVVVVLM PPEQLRNSSF HFLRELSRVL
1610 1620 1630 1640 1650
HTNVVFKRDA HGQQMIFPYY GREEELRKHP IKRAAEGWAA PDALLGQVKA
1660 1670 1680 1690 1700
SLLPGGSEGG RRRRELDPMD VRGSIVYLEI DNRQCVQASS QCFQSATDVA
1710 1720 1730 1740 1750
AFLGALASLG SLNIPYKIEA VQSETVEPPP PAQLHFMYVA AAAFVLLFFV
1760 1770 1780 1790 1800
GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA
1810 1820 1830 1840 1850
SDGALMDDNQ NEWGDEDLET KKFRFEEPVV LPDLDDQTDH RQWTQQHLDA
1860 1870 1880 1890 1900
ADLRMSAMAP TPPQGEVDAD CMDVNVRGPD GFTPLMIASC SGGGLETGNS
1910 1920 1930 1940 1950
EEEEDAPAVI SDFIYQGASL HNQTDRTGET ALHLAARYSR SDAAKRLLEA
1960 1970 1980 1990 2000
SADANIQDNM GRTPLHAAVS ADAQGVFQIL IRNRATDLDA RMHDGTTPLI
2010 2020 2030 2040 2050
LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN VDAAVVLLKN
2060 2070 2080 2090 2100
GANKDMQNNR EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI
2110 2120 2130 2140 2150
AQERMHHDIV RLLDEYNLVR SPQLHGAPLG GTPTLSPPLC SPNGYLGSLK
2160 2170 2180 2190 2200
PGVQGKKVRK PSSKGLACGS KEAKDLKARR KKSQDGKGCL LDSSGMLSPV
2210 2220 2230 2240 2250
DSLESPHGYL SDVASPPLLP SPFQQSPSVP LNHLPGMPDT HLGIGHLNVA
2260 2270 2280 2290 2300
AKPEMAALGG GGRLAFETGP PRLSHLPVAS GTSTVLGSSS GGALNFTVGG
2310 2320 2330 2340 2350
STSLNGQCEW LSRLQSGMVP NQYNPLRGSV APGPLSTQAP SLQHGMVGPL
2360 2370 2380 2390 2400
HSSLAASALS QMMSYQGLPS TRLATQPHLV QTQQVQPQNL QMQQQNLQPA
2410 2420 2430 2440 2450
NIQQQQSLQP PPPPPQPHLG VSSAASGHLG RSFLSGEPSQ ADVQPLGPSS
2460 2470 2480 2490 2500
LAVHTILPQE SPALPTSLPS SLVPPVTAAQ FLTPPSQHSY SSPVDNTPSH
2510 2520 2530 2540 2550
QLQVPEHPFL TPSPESPDQW SSSSPHSNVS DWSEGVSSPP TSMQSQIARI
PEAFK
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A7P0T8U6 | A0A7P0T8U6_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 2,517 | Annotation score: | ||
A0A7P0T8W1 | A0A7P0T8W1_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 2,515 | Annotation score: | ||
A0A7P0TB20 | A0A7P0TB20_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 2,517 | Annotation score: | ||
A0A7P0TA56 | A0A7P0TA56_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 1,754 | Annotation score: | ||
A0A7P0TAK8 | A0A7P0TAK8_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 1,748 | Annotation score: | ||
A0A7P0TBG2 | A0A7P0TBG2_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 823 | Annotation score: | ||
A0A7P0Z4H9 | A0A7P0Z4H9_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 864 | Annotation score: | ||
A0A7P0T9V1 | A0A7P0T9V1_HUMAN | Neurogenic locus notch homolog prot... | NOTCH1 | 53 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 187 | G → R in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 187 | G → R in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 282 | R → P in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 282 | R → P in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 477 | I → M in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 477 | I → M in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 614 – 615 | HG → LR in AAG33848 (Ref. 1) Curated | 2 | |
Sequence conflicti | 614 – 615 | HG → LR in AAA60614 (PubMed:1831692).Curated | 2 | |
Sequence conflicti | 621 | R → P in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 621 | R → P in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 677 | I → S in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 677 | I → S in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 775 | Y → I in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 775 | Y → I in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 803 | Q → K in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 803 | Q → K in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 860 – 862 | GWQ → AGAK in AAG33848 (Ref. 1) Curated | 3 | |
Sequence conflicti | 860 – 862 | GWQ → AGAK in AAA60614 (PubMed:1831692).Curated | 3 | |
Sequence conflicti | 1021 | D → V in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 1021 | D → V in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 1028 | Q → R in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 1028 | Q → R in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 1032 | H → L in AAG33848 (Ref. 1) Curated | 1 | |
Sequence conflicti | 1032 | H → L in AAA60614 (PubMed:1831692).Curated | 1 | |
Sequence conflicti | 1040 – 1043 | CGSY → RGLH in AAG33848 (Ref. 1) Curated | 4 | |
Sequence conflicti | 1040 – 1043 | CGSY → RGLH in AAA60614 (PubMed:1831692).Curated | 4 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034898 | 300 | Q → R. Corresponds to variant dbSNP:rs11574885Ensembl. | 1 | |
Natural variantiVAR_071960 | 429 | C → R in AOS5. 1 PublicationCorresponds to variant dbSNP:rs587777736EnsemblClinVar. | 1 | |
Natural variantiVAR_048990 | 879 | R → W. Corresponds to variant dbSNP:rs11574895Ensembl. | 1 | |
Natural variantiVAR_071961 | 1496 | C → Y in AOS5. 1 PublicationCorresponds to variant dbSNP:rs587781259EnsemblClinVar. | 1 | |
Natural variantiVAR_046618 | 1671 | V → I. Corresponds to variant dbSNP:rs2229968EnsemblClinVar. | 1 | |
Natural variantiVAR_071962 | 1989 | D → N in AOS5. 1 PublicationCorresponds to variant dbSNP:rs587777734EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF308602 mRNA Translation: AAG33848.1 AL592301 Genomic DNA No translation available. AL354671 Genomic DNA No translation available. M73980 mRNA Translation: AAA60614.1 AB209873 mRNA Translation: BAD93110.1 |
CCDSi | CCDS43905.1 |
PIRi | A40043 |
RefSeqi | NP_060087.3, NM_017617.4 |
Genome annotation databases
Ensembli | ENST00000651671; ENSP00000498587; ENSG00000148400 |
GeneIDi | 4851 |
KEGGi | hsa:4851 |
MANE-Selecti | ENST00000651671.1; ENSP00000498587.1; NM_017617.5; NP_060087.3 |
UCSCi | uc004chz.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF308602 mRNA Translation: AAG33848.1 AL592301 Genomic DNA No translation available. AL354671 Genomic DNA No translation available. M73980 mRNA Translation: AAA60614.1 AB209873 mRNA Translation: BAD93110.1 |
CCDSi | CCDS43905.1 |
PIRi | A40043 |
RefSeqi | NP_060087.3, NM_017617.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1PB5 | NMR | - | A | 1446-1480 | [»] | |
1TOZ | NMR | - | A | 411-526 | [»] | |
1YYH | X-ray | 1.90 | A/B | 1872-2114 | [»] | |
2F8X | X-ray | 3.25 | K | 1872-2126 | [»] | |
2F8Y | X-ray | 1.55 | A/B | 1905-2126 | [»] | |
2HE0 | X-ray | 1.90 | A/B | 1872-2114 | [»] | |
2VJ3 | X-ray | 2.60 | A | 411-526 | [»] | |
3ETO | X-ray | 2.00 | A/B | 1446-1733 | [»] | |
3I08 | X-ray | 3.20 | A/C | 1446-1664 | [»] | |
B/D | 1665-1733 | [»] | ||||
3L95 | X-ray | 2.19 | X/Y | 1448-1728 | [»] | |
3NBN | X-ray | 3.45 | B/E | 1872-2126 | [»] | |
3V79 | X-ray | 3.85 | K | 1872-2126 | [»] | |
R | 1759-1777 | [»] | ||||
4CUD | X-ray | 1.85 | A | 411-526 | [»] | |
4CUE | X-ray | 3.00 | A | 411-526 | [»] | |
4CUF | X-ray | 2.29 | A | 411-526 | [»] | |
4D0E | X-ray | 1.61 | A | 411-526 | [»] | |
4D0F | X-ray | 2.80 | A | 411-526 | [»] | |
5FM9 | X-ray | 2.92 | A | 140-294 | [»] | |
5FMA | X-ray | 2.46 | A/B | 142-294 | [»] | |
5KZO | NMR | - | A | 1721-1771 | [»] | |
5L0R | X-ray | 1.50 | B | 452-491 | [»] | |
5UB5 | X-ray | 2.09 | B | 452-491 | [»] | |
6IDF | electron microscopy | 2.70 | E | 1721-1821 | [»] | |
6PY8 | X-ray | 3.75 | F/K | 1759-2127 | [»] | |
SASBDBi | P46531 | |||||
SMRi | P46531 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110913, 302 interactors |
CORUMi | P46531 |
DIPi | DIP-29919N |
IntActi | P46531, 181 interactors |
MINTi | P46531 |
STRINGi | 9606.ENSP00000277541 |
Chemistry databases
BindingDBi | P46531 |
ChEMBLi | CHEMBL2146346 |
GuidetoPHARMACOLOGYi | 2861 |
Protein family/group databases
TCDBi | 9.B.87.1.12, the selenoprotein p receptor (selp-receptor) family |
PTM databases
GlyGeni | P46531, 54 sites, 2 O-linked glycans (9 sites) |
iPTMneti | P46531 |
PhosphoSitePlusi | P46531 |
Genetic variation databases
BioMutai | NOTCH1 |
DMDMi | 206729936 |
Proteomic databases
EPDi | P46531 |
jPOSTi | P46531 |
MassIVEi | P46531 |
MaxQBi | P46531 |
PaxDbi | P46531 |
PeptideAtlasi | P46531 |
PRIDEi | P46531 |
ProteomicsDBi | 55742 |
Protocols and materials databases
ABCDi | P46531, 196 sequenced antibodies |
Antibodypediai | 8424, 1378 antibodies from 53 providers |
DNASUi | 4851 |
Genome annotation databases
Ensembli | ENST00000651671; ENSP00000498587; ENSG00000148400 |
GeneIDi | 4851 |
KEGGi | hsa:4851 |
MANE-Selecti | ENST00000651671.1; ENSP00000498587.1; NM_017617.5; NP_060087.3 |
UCSCi | uc004chz.4, human |
Organism-specific databases
CTDi | 4851 |
DisGeNETi | 4851 |
GeneCardsi | NOTCH1 |
GeneReviewsi | NOTCH1 |
HGNCi | HGNC:7881, NOTCH1 |
HPAi | ENSG00000148400, Low tissue specificity |
MalaCardsi | NOTCH1 |
MIMi | 109730, phenotype 190198, gene 616028, phenotype |
neXtProti | NX_P46531 |
OpenTargetsi | ENSG00000148400 |
Orphaneti | 974, Adams-Oliver syndrome 402075, Familial bicuspid aortic valve |
PharmGKBi | PA31683 |
VEuPathDBi | HostDB:ENSG00000148400 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1217, Eukaryota |
GeneTreei | ENSGT00940000157157 |
HOGENOMi | CLU_000576_2_0_1 |
InParanoidi | P46531 |
OMAi | NEGSCLD |
OrthoDBi | 7525at2759 |
PhylomeDBi | P46531 |
TreeFami | TF351641 |
Enzyme and pathway databases
PathwayCommonsi | P46531 |
Reactomei | R-HSA-1912399, Pre-NOTCH Processing in the Endoplasmic Reticulum R-HSA-1912408, Pre-NOTCH Transcription and Translation R-HSA-1912420, Pre-NOTCH Processing in Golgi R-HSA-210744, Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells R-HSA-2122947, NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-2644606, Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2644607, Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling R-HSA-2660826, Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant R-HSA-2691232, Constitutive Signaling by NOTCH1 HD Domain Mutants R-HSA-2894862, Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-350054, Notch-HLH transcription pathway R-HSA-5083630, Defective LFNG causes SCDO3 R-HSA-8941856, RUNX3 regulates NOTCH signaling R-HSA-9013508, NOTCH3 Intracellular Domain Regulates Transcription R-HSA-9013695, NOTCH4 Intracellular Domain Regulates Transcription |
SignaLinki | P46531 |
SIGNORi | P46531 |
Miscellaneous databases
BioGRID-ORCSi | 4851, 10 hits in 1055 CRISPR screens |
ChiTaRSi | NOTCH1, human |
EvolutionaryTracei | P46531 |
GeneWikii | Notch-1 |
GenomeRNAii | 4851 |
Pharosi | P46531, Tchem |
PROi | PR:P46531 |
RNActi | P46531, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000148400, Expressed in ventricular zone and 229 other tissues |
Genevisiblei | P46531, HS |
Family and domain databases
DisProti | DP01104 |
Gene3Di | 1.25.40.20, 1 hit |
IDEALi | IID00199 |
InterProi | View protein in InterPro IPR002110, Ankyrin_rpt IPR036770, Ankyrin_rpt-contain_sf IPR001881, EGF-like_Ca-bd_dom IPR013032, EGF-like_CS IPR000742, EGF-like_dom IPR000152, EGF-type_Asp/Asn_hydroxyl_site IPR018097, EGF_Ca-bd_CS IPR009030, Growth_fac_rcpt_cys_sf IPR008297, Notch IPR035993, Notch-like_dom_sf IPR022362, Notch_1 IPR024600, Notch_C IPR000800, Notch_dom IPR010660, Notch_NOD_dom IPR011656, Notch_NODP_dom |
Pfami | View protein in Pfam PF12796, Ank_2, 2 hits PF00008, EGF, 25 hits PF07645, EGF_CA, 4 hits PF12661, hEGF, 2 hits PF06816, NOD, 1 hit PF07684, NODP, 1 hit PF00066, Notch, 3 hits |
PIRSFi | PIRSF002279, Notch, 1 hit |
PRINTSi | PR01452, LNOTCHREPEAT PR01984, NOTCH1 |
SMARTi | View protein in SMART SM00248, ANK, 6 hits SM01334, DUF3454, 1 hit SM00181, EGF, 36 hits SM00179, EGF_CA, 33 hits SM00004, NL, 3 hits SM01338, NOD, 1 hit SM01339, NODP, 1 hit |
SUPFAMi | SSF48403, SSF48403, 1 hit SSF57184, SSF57184, 6 hits SSF90193, SSF90193, 3 hits |
PROSITEi | View protein in PROSITE PS50297, ANK_REP_REGION, 1 hit PS50088, ANK_REPEAT, 4 hits PS00010, ASX_HYDROXYL, 22 hits PS00022, EGF_1, 35 hits PS01186, EGF_2, 27 hits PS50026, EGF_3, 36 hits PS01187, EGF_CA, 20 hits PS50258, LNR, 3 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | NOTC1_HUMAN | |
Accessioni | P46531Primary (citable) accession number: P46531 Secondary accession number(s): Q59ED8, Q5SXM3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
Last sequence update: | September 23, 2008 | |
Last modified: | February 23, 2022 | |
This is version 246 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families