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P46531

- NOTC1_HUMAN

UniProt

P46531 - NOTC1_HUMAN

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Protein

Neurogenic locus notch homolog protein 1

Gene
NOTCH1, TAN1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 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 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi1457 – 14571Calcium; via carbonyl oxygen
Metal bindingi1460 – 14601Calcium
Metal bindingi1475 – 14751Calcium
Metal bindingi1478 – 14781Calcium
Sitei1664 – 16652Cleavage; by furin-like protease By similarity
Sitei1710 – 17112Cleavage; by ADAM17 By similarity
Sitei1720 – 17212Cleavage; by ADAM17

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. chromatin DNA binding Source: Ensembl
  3. core promoter binding Source: UniProtKB
  4. enzyme binding Source: UniProtKB
  5. enzyme inhibitor activity Source: UniProtKB
  6. protein binding Source: UniProtKB
  7. receptor activity Source: InterPro
  8. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
  9. sequence-specific DNA binding Source: Ensembl
  10. sequence-specific DNA binding transcription factor activity Source: Ensembl

GO - Biological processi

  1. anagen Source: Ensembl
  2. aortic valve morphogenesis Source: BHF-UCL
  3. apoptotic process involved in embryonic digit morphogenesis Source: Ensembl
  4. arterial endothelial cell differentiation Source: BHF-UCL
  5. atrioventricular node development Source: Ensembl
  6. atrioventricular valve morphogenesis Source: BHF-UCL
  7. auditory receptor cell fate commitment Source: Ensembl
  8. axonogenesis Source: Ensembl
  9. branching morphogenesis of an epithelial tube Source: Ensembl
  10. cardiac atrium morphogenesis Source: BHF-UCL
  11. cardiac chamber formation Source: BHF-UCL
  12. cardiac epithelial to mesenchymal transition Source: BHF-UCL
  13. cardiac left ventricle morphogenesis Source: BHF-UCL
  14. cardiac muscle cell proliferation Source: Ensembl
  15. cardiac muscle tissue morphogenesis Source: BHF-UCL
  16. cardiac right atrium morphogenesis Source: BHF-UCL
  17. cardiac right ventricle formation Source: Ensembl
  18. cardiac septum morphogenesis Source: BHF-UCL
  19. cardiac vascular smooth muscle cell development Source: BHF-UCL
  20. cardiac ventricle morphogenesis Source: BHF-UCL
  21. cell fate specification Source: Ensembl
  22. cell migration involved in endocardial cushion formation Source: BHF-UCL
  23. cellular response to follicle-stimulating hormone stimulus Source: BHF-UCL
  24. cellular response to vascular endothelial growth factor stimulus Source: UniProtKB
  25. cilium morphogenesis Source: UniProtKB
  26. collecting duct development Source: Ensembl
  27. compartment pattern specification Source: Ensembl
  28. coronary artery morphogenesis Source: BHF-UCL
  29. coronary vein morphogenesis Source: BHF-UCL
  30. determination of left/right symmetry Source: BHF-UCL
  31. distal tubule development Source: Ensembl
  32. embryonic hindlimb morphogenesis Source: Ensembl
  33. endocardial cell differentiation Source: BHF-UCL
  34. endocardial cushion morphogenesis Source: BHF-UCL
  35. endocardium development Source: BHF-UCL
  36. endocardium morphogenesis Source: BHF-UCL
  37. endoderm development Source: Ensembl
  38. epithelial to mesenchymal transition Source: BHF-UCL
  39. epithelial to mesenchymal transition involved in endocardial cushion formation Source: BHF-UCL
  40. forebrain development Source: Ensembl
  41. foregut morphogenesis Source: Ensembl
  42. gene expression Source: Reactome
  43. glial cell differentiation Source: Ensembl
  44. glomerular mesangial cell development Source: Ensembl
  45. growth involved in heart morphogenesis Source: BHF-UCL
  46. hair follicle morphogenesis Source: Ensembl
  47. heart development Source: DFLAT
  48. heart looping Source: BHF-UCL
  49. heart trabecula morphogenesis Source: BHF-UCL
  50. humoral immune response Source: Ensembl
  51. immune response Source: UniProtKB
  52. inflammatory response to antigenic stimulus Source: Ensembl
  53. interleukin-4 secretion Source: Ensembl
  54. in utero embryonic development Source: Ensembl
  55. keratinocyte differentiation Source: Ensembl
  56. left/right axis specification Source: Ensembl
  57. liver development Source: Ensembl
  58. lung development Source: Ensembl
  59. mesenchymal cell development Source: BHF-UCL
  60. mitral valve formation Source: BHF-UCL
  61. negative regulation of anoikis Source: BHF-UCL
  62. negative regulation of BMP signaling pathway Source: BHF-UCL
  63. negative regulation of calcium ion-dependent exocytosis Source: Ensembl
  64. negative regulation of canonical Wnt signaling pathway Source: Ensembl
  65. negative regulation of catalytic activity Source: UniProtKB
  66. negative regulation of cell migration involved in sprouting angiogenesis Source: UniProtKB
  67. negative regulation of cell proliferation Source: UniProtKB
  68. negative regulation of cell-substrate adhesion Source: BHF-UCL
  69. negative regulation of endothelial cell chemotaxis Source: UniProtKB
  70. negative regulation of glial cell proliferation Source: UniProtKB
  71. negative regulation of myoblast differentiation Source: UniProtKB
  72. negative regulation of myotube differentiation Source: UniProtKB
  73. negative regulation of neurogenesis Source: UniProtKB
  74. negative regulation of oligodendrocyte differentiation Source: UniProtKB
  75. negative regulation of ossification Source: BHF-UCL
  76. negative regulation of osteoblast differentiation Source: BHF-UCL
  77. negative regulation of photoreceptor cell differentiation Source: Ensembl
  78. negative regulation of pro-B cell differentiation Source: UniProtKB
  79. negative regulation of stem cell differentiation Source: UniProtKB
  80. negative regulation of transcription, DNA-templated Source: BHF-UCL
  81. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  82. neural tube development Source: Ensembl
  83. neuronal stem cell maintenance Source: UniProtKB
  84. Notch receptor processing Source: Reactome
  85. Notch signaling involved in heart development Source: BHF-UCL
  86. Notch signaling pathway Source: UniProtKB
  87. Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation Source: Ensembl
  88. pericardium morphogenesis Source: BHF-UCL
  89. positive regulation of apoptotic process Source: Ensembl
  90. positive regulation of astrocyte differentiation Source: UniProtKB
  91. positive regulation of BMP signaling pathway Source: UniProtKB
  92. positive regulation of cardiac muscle cell proliferation Source: BHF-UCL
  93. positive regulation of cell migration Source: BHF-UCL
  94. positive regulation of cell proliferation Source: UniProtKB
  95. positive regulation of epithelial cell proliferation Source: Ensembl
  96. positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
  97. positive regulation of JAK-STAT cascade Source: UniProtKB
  98. positive regulation of keratinocyte differentiation Source: Ensembl
  99. positive regulation of transcription, DNA-templated Source: UniProtKB
  100. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  101. positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
  102. positive regulation of transcription of Notch receptor target Source: BHF-UCL
  103. prostate gland epithelium morphogenesis Source: Ensembl
  104. pulmonary valve morphogenesis Source: BHF-UCL
  105. regulation of epithelial cell proliferation involved in prostate gland development Source: Ensembl
  106. regulation of extracellular matrix assembly Source: BHF-UCL
  107. regulation of somitogenesis Source: Ensembl
  108. regulation of transcription, DNA-templated Source: UniProtKB
  109. regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation Source: BHF-UCL
  110. response to muramyl dipeptide Source: Ensembl
  111. secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development Source: Ensembl
  112. skeletal muscle cell differentiation Source: Ensembl
  113. somatic stem cell division Source: Ensembl
  114. sprouting angiogenesis Source: Ensembl
  115. transcription initiation from RNA polymerase II promoter Source: Reactome
  116. tube formation Source: UniProtKB
  117. vasculogenesis involved in coronary vascular morphogenesis Source: BHF-UCL
  118. venous endothelial cell differentiation Source: BHF-UCL
  119. ventricular septum morphogenesis Source: BHF-UCL
  120. ventricular trabecula myocardium morphogenesis Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein, Receptor

Keywords - Biological processi

Angiogenesis, Differentiation, Notch signaling pathway, Transcription, Transcription regulation

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_118568. Pre-NOTCH Transcription and Translation.
REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_118722. Pre-NOTCH Processing in the Endoplasmic Reticulum.
REACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_118798. Pre-NOTCH Processing in Golgi.
REACT_13673. Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
REACT_14835. Notch-HLH transcription pathway.
REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
REACT_160106. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
REACT_160305. Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling.
SignaLinkiP46531.

Names & Taxonomyi

Protein namesi
Recommended name:
Neurogenic locus notch homolog protein 1
Short 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 9

Organism-specific databases

HGNCiHGNC:7881. NOTCH1.

Subcellular locationi

Chain Notch 1 intracellular domain : Nucleus By similarity
Note: Following proteolytical processing NICD is translocated to the nucleus By similarity.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini19 – 17351717Extracellular Reviewed predictionAdd
BLAST
Transmembranei1736 – 175621Helical; Reviewed predictionAdd
BLAST
Topological domaini1757 – 2555799Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: Ensembl
  2. cytosol Source: Reactome
  3. endoplasmic reticulum membrane Source: Reactome
  4. extracellular region Source: Reactome
  5. Golgi membrane Source: Reactome
  6. integral component of membrane Source: UniProtKB-KW
  7. MAML1-RBP-Jkappa- ICN1 complex Source: UniProtKB
  8. nucleoplasm Source: Reactome
  9. nucleus Source: UniProtKB
  10. plasma membrane Source: Reactome
  11. receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Aortic valve disease 1 (AOVD1) [MIM:109730]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication

Organism-specific databases

MIMi109730. phenotype.
Orphaneti1244. Bicuspid aortic valve.
PharmGKBiPA31683.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818 Reviewed predictionAdd
BLAST
Chaini19 – 25552537Neurogenic locus notch homolog protein 1PRO_0000007674Add
BLAST
Chaini1721 – 2555835Notch 1 extracellular truncation By similarityPRO_0000007675Add
BLAST
Chaini1754 – 2555802Notch 1 intracellular domain By similarityPRO_0000007676Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi24 ↔ 37 By similarity
Disulfide bondi31 ↔ 46 By similarity
Glycosylationi41 – 411N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi48 ↔ 57 By similarity
Disulfide bondi63 ↔ 74 By similarity
Glycosylationi65 – 651O-linked (Glc...) By similarity
Disulfide bondi68 ↔ 87 By similarity
Glycosylationi73 – 731O-linked (Fuc...) By similarity
Disulfide bondi89 ↔ 98 By similarity
Disulfide bondi106 ↔ 117 By similarity
Disulfide bondi111 ↔ 127 By similarity
Glycosylationi116 – 1161O-linked (Fuc...) By similarity
Disulfide bondi129 ↔ 138 By similarity
Disulfide bondi144 ↔ 155 By similarity
Glycosylationi146 – 1461O-linked (Glc...) By similarity
Disulfide bondi149 ↔ 164 By similarity
Disulfide bondi166 ↔ 175 By similarity
Disulfide bondi182 ↔ 195 By similarity
Disulfide bondi189 ↔ 204 By similarity
Glycosylationi194 – 1941O-linked (Fuc...) By similarity
Disulfide bondi206 ↔ 215 By similarity
Disulfide bondi222 ↔ 233 By similarity
Disulfide bondi227 ↔ 243 By similarity
Glycosylationi232 – 2321O-linked (Fuc...); alternate1 Publication
Glycosylationi232 – 2321O-linked (GalNAc...); alternate1 Publication
Disulfide bondi245 ↔ 254 By similarity
Disulfide bondi261 ↔ 272 By similarity
Disulfide bondi266 ↔ 281 By similarity
Disulfide bondi283 ↔ 292 By similarity
Disulfide bondi299 ↔ 312 By similarity
Disulfide bondi306 ↔ 321 By similarity
Disulfide bondi323 ↔ 332 By similarity
Disulfide bondi339 ↔ 350 By similarity
Glycosylationi341 – 3411O-linked (Glc...) By similarity
Disulfide bondi344 ↔ 359 By similarity
Disulfide bondi361 ↔ 370 By similarity
Disulfide bondi376 ↔ 387 By similarity
Glycosylationi378 – 3781O-linked (Glc...) By similarity
Disulfide bondi381 ↔ 398 By similarity
Disulfide bondi400 ↔ 409 By similarity
Disulfide bondi416 ↔ 429 By similarity
Disulfide bondi423 ↔ 438 By similarity
Disulfide bondi440 ↔ 449 By similarity
Disulfide bondi456 ↔ 467 By similarity
Glycosylationi458 – 4581O-linked (Glc...) By similarity
Disulfide bondi461 ↔ 476 By similarity
Glycosylationi466 – 4661O-linked (Fuc...) By similarity
Disulfide bondi478 ↔ 487 By similarity
Disulfide bondi494 ↔ 505 By similarity
Glycosylationi496 – 4961O-linked (Glc...) By similarity
Disulfide bondi499 ↔ 514 By similarity
Disulfide bondi516 ↔ 525 By similarity
Disulfide bondi532 ↔ 543 By similarity
Glycosylationi534 – 5341O-linked (Glc...) By similarity
Disulfide bondi537 ↔ 552 By similarity
Disulfide bondi554 ↔ 563 By similarity
Disulfide bondi570 ↔ 580 By similarity
Disulfide bondi575 ↔ 589 By similarity
Disulfide bondi591 ↔ 600 By similarity
Disulfide bondi607 ↔ 618 By similarity
Glycosylationi609 – 6091O-linked (Glc...) By similarity
Disulfide bondi612 ↔ 627 By similarity
Disulfide bondi629 ↔ 638 By similarity
Disulfide bondi645 ↔ 655 By similarity
Glycosylationi647 – 6471O-linked (Glc...) By similarity
Disulfide bondi650 ↔ 664 By similarity
Disulfide bondi666 ↔ 675 By similarity
Disulfide bondi682 ↔ 693 By similarity
Disulfide bondi687 ↔ 702 By similarity
Disulfide bondi704 ↔ 713 By similarity
Disulfide bondi720 ↔ 730 By similarity
Glycosylationi722 – 7221O-linked (Glc...) By similarity
Disulfide bondi725 ↔ 739 By similarity
Disulfide bondi741 ↔ 750 By similarity
Disulfide bondi757 ↔ 768 By similarity
Glycosylationi759 – 7591O-linked (Glc...) By similarity
Disulfide bondi762 ↔ 777 By similarity
Glycosylationi767 – 7671O-linked (Fuc...) By similarity
Disulfide bondi779 ↔ 788 By similarity
Disulfide bondi795 ↔ 806 By similarity
Glycosylationi797 – 7971O-linked (Glc...) By similarity
Disulfide bondi800 ↔ 815 By similarity
Glycosylationi805 – 8051O-linked (Fuc...) By similarity
Disulfide bondi817 ↔ 826 By similarity
Disulfide bondi833 ↔ 844 By similarity
Disulfide bondi838 ↔ 855 By similarity
Disulfide bondi857 ↔ 866 By similarity
Disulfide bondi873 ↔ 884 By similarity
Disulfide bondi878 ↔ 893 By similarity
Disulfide bondi895 ↔ 904 By similarity
Disulfide bondi911 ↔ 922 By similarity
Disulfide bondi916 ↔ 931 By similarity
Disulfide bondi933 ↔ 942 By similarity
Disulfide bondi949 ↔ 960 By similarity
Glycosylationi951 – 9511O-linked (Glc...) By similarity
Disulfide bondi954 ↔ 969 By similarity
Glycosylationi959 – 9591N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi971 ↔ 980 By similarity
Disulfide bondi987 ↔ 998 By similarity
Disulfide bondi992 ↔ 1007 By similarity
Disulfide bondi1009 ↔ 1018 By similarity
Disulfide bondi1025 ↔ 1036 By similarity
Glycosylationi1027 – 10271O-linked (Glc...) By similarity
Disulfide bondi1030 ↔ 1045 By similarity
Glycosylationi1035 – 10351O-linked (Fuc...) By similarity
Disulfide bondi1047 ↔ 1056 By similarity
Disulfide bondi1063 ↔ 1074 By similarity
Glycosylationi1065 – 10651O-linked (Glc...) By similarity
Disulfide bondi1068 ↔ 1083 By similarity
Disulfide bondi1085 ↔ 1094 By similarity
Disulfide bondi1101 ↔ 1122 By similarity
Disulfide bondi1116 ↔ 1131 By similarity
Disulfide bondi1133 ↔ 1142 By similarity
Disulfide bondi1149 ↔ 1160 By similarity
Disulfide bondi1154 ↔ 1169 By similarity
Disulfide bondi1171 ↔ 1180 By similarity
Glycosylationi1179 – 11791N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1187 ↔ 1198 By similarity
Glycosylationi1189 – 11891O-linked (Glc...) By similarity
Disulfide bondi1192 ↔ 1207 By similarity
Glycosylationi1197 – 11971O-linked (Fuc...) By similarity
Disulfide bondi1209 ↔ 1218 By similarity
Disulfide bondi1225 ↔ 1244 By similarity
Disulfide bondi1238 ↔ 1253 By similarity
Glycosylationi1241 – 12411N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1255 ↔ 1264 By similarity
Disulfide bondi1271 ↔ 1284 By similarity
Glycosylationi1273 – 12731O-linked (Glc...) By similarity
Disulfide bondi1276 ↔ 1293 By similarity
Disulfide bondi1295 ↔ 1304 By similarity
Disulfide bondi1311 ↔ 1322 By similarity
Disulfide bondi1316 ↔ 1334 By similarity
Disulfide bondi1336 ↔ 1345 By similarity
Disulfide bondi1352 ↔ 1363 By similarity
Disulfide bondi1357 ↔ 1372 By similarity
Glycosylationi1362 – 13621O-linked (Fuc...) By similarity
Disulfide bondi1374 ↔ 1383 By similarity
Disulfide bondi1391 ↔ 1403 By similarity
Disulfide bondi1397 ↔ 1414 By similarity
Glycosylationi1402 – 14021O-linked (Fuc...); alternate1 Publication
Glycosylationi1402 – 14021O-linked (GalNAc...); alternate1 Publication
Disulfide bondi1416 ↔ 1425 By similarity
Disulfide bondi1449 ↔ 14721 Publication
Disulfide bondi1454 ↔ 14671 Publication
Disulfide bondi1463 ↔ 14791 Publication
Glycosylationi1489 – 14891N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1490 ↔ 1514 By similarity
Disulfide bondi1496 ↔ 1509 By similarity
Disulfide bondi1505 ↔ 1521 By similarity
Disulfide bondi1536 ↔ 1549 By similarity
Disulfide bondi1545 ↔ 1561 By similarity
Glycosylationi1587 – 15871N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1725 – 17251O-linked (GalNAc...)1 Publication
Cross-linki1759 – 1759Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Modified residuei1955 – 19551(3S)-3-hydroxyasparagine; by HIF1AN; partial1 Publication
Modified residuei2022 – 20221(3S)-3-hydroxyasparagine; by HIF1AN By similarity

Post-translational modificationi

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.1 Publication
Phosphorylated By similarity.
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).1 Publication
Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. 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.1 Publication
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.

Keywords - PTMi

Disulfide bond, Glycoprotein, Hydroxylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP46531.
PaxDbiP46531.
PRIDEiP46531.

PTM databases

PhosphoSiteiP46531.

Expressioni

Tissue specificityi

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.

Gene expression databases

ArrayExpressiP46531.
BgeeiP46531.
CleanExiHS_NOTCH1.
GenevestigatoriP46531.

Organism-specific databases

HPAiCAB008112.
CAB022466.

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. Notch 1 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. 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. 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.9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NFKB1P198382EBI-636374,EBI-300010
PIN1Q135269EBI-636374,EBI-714158
RBPJQ063303EBI-636374,EBI-632552
SNW1Q135733EBI-636374,EBI-632715
XIAPP981704EBI-636374,EBI-517127

Protein-protein interaction databases

BioGridi110913. 179 interactions.
DIPiDIP-29919N.
IntActiP46531. 21 interactions.
MINTiMINT-1417018.
STRINGi9606.ENSP00000277541.

Structurei

Secondary structure

1
2555
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi415 – 4173
Beta strandi418 – 4203
Beta strandi422 – 4243
Beta strandi428 – 4325
Beta strandi435 – 4395
Beta strandi444 – 4463
Turni455 – 4584
Beta strandi466 – 4705
Beta strandi473 – 4775
Beta strandi482 – 4843
Turni493 – 4964
Turni500 – 5023
Beta strandi504 – 5074
Beta strandi512 – 5154
Beta strandi520 – 5223
Helixi1448 – 14503
Helixi1452 – 14576
Beta strandi1460 – 14623
Helixi1465 – 14673
Helixi1470 – 14723
Helixi1473 – 14764
Turni1477 – 14826
Turni1486 – 14894
Helixi1492 – 14943
Helixi1496 – 14983
Turni1499 – 15013
Beta strandi1502 – 15043
Helixi1507 – 15093
Helixi1512 – 15198
Turni1530 – 15323
Helixi1533 – 15397
Beta strandi1542 – 15443
Helixi1547 – 15493
Helixi1552 – 15598
Beta strandi1563 – 15653
Beta strandi1571 – 158010
Helixi1582 – 15876
Helixi1589 – 160012
Beta strandi1602 – 16065
Beta strandi1616 – 16205
Beta strandi1672 – 168110
Helixi1685 – 16884
Helixi1696 – 170813
Beta strandi1714 – 17163
Beta strandi1718 – 17247
Helixi1884 – 18907
Helixi1909 – 19146
Turni1925 – 19273
Helixi1931 – 19377
Helixi1941 – 19499
Helixi1964 – 19707
Helixi1974 – 19829
Beta strandi1983 – 19853
Helixi1998 – 20058
Helixi2008 – 20169
Helixi2031 – 20377
Helixi2041 – 20499
Helixi2064 – 20718
Helixi2074 – 20829
Helixi2097 – 21037
Helixi2107 – 21159

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1PB5NMR-A1446-1480[»]
1TOZNMR-A411-526[»]
1YYHX-ray1.90A/B1872-2114[»]
2F8XX-ray3.25K1872-2126[»]
2F8YX-ray1.55A/B1905-2126[»]
2HE0X-ray1.90A/B1872-2114[»]
2VJ3X-ray2.60A411-526[»]
3ETOX-ray2.00A/B1446-1733[»]
3I08X-ray3.20A/C1446-1664[»]
B/D1665-1733[»]
3L95X-ray2.19X/Y1448-1728[»]
3NBNX-ray3.45B/E1872-2126[»]
3V79X-ray3.85K1872-2126[»]
R1759-1777[»]
4CUDX-ray1.85A411-526[»]
4CUEX-ray3.00A411-526[»]
4CUFX-ray2.29A411-526[»]
4D0EX-ray1.61A411-526[»]
4D0FX-ray2.80A411-526[»]
ProteinModelPortaliP46531.
SMRiP46531. Positions 411-526, 1448-1728, 1883-2122.

Miscellaneous databases

EvolutionaryTraceiP46531.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 5839EGF-like 1Add
BLAST
Domaini59 – 9941EGF-like 2Add
BLAST
Domaini102 – 13938EGF-like 3Add
BLAST
Domaini140 – 17637EGF-like 4Add
BLAST
Domaini178 – 21639EGF-like 5; calcium-binding Reviewed predictionAdd
BLAST
Domaini218 – 25538EGF-like 6Add
BLAST
Domaini257 – 29337EGF-like 7; calcium-binding Reviewed predictionAdd
BLAST
Domaini295 – 33339EGF-like 8; calcium-binding Reviewed predictionAdd
BLAST
Domaini335 – 37137EGF-like 9; calcium-binding Reviewed predictionAdd
BLAST
Domaini372 – 41039EGF-like 10Add
BLAST
Domaini412 – 45039EGF-like 11; calcium-binding Reviewed predictionAdd
BLAST
Domaini452 – 48837EGF-like 12; calcium-binding Reviewed predictionAdd
BLAST
Domaini490 – 52637EGF-like 13; calcium-binding Reviewed predictionAdd
BLAST
Domaini528 – 56437EGF-like 14; calcium-binding Reviewed predictionAdd
BLAST
Domaini566 – 60136EGF-like 15; calcium-binding Reviewed predictionAdd
BLAST
Domaini603 – 63937EGF-like 16; calcium-binding Reviewed predictionAdd
BLAST
Domaini641 – 67636EGF-like 17; calcium-binding Reviewed predictionAdd
BLAST
Domaini678 – 71437EGF-like 18; calcium-binding Reviewed predictionAdd
BLAST
Domaini716 – 75136EGF-like 19; calcium-binding Reviewed predictionAdd
BLAST
Domaini753 – 78937EGF-like 20Add
BLAST
Domaini791 – 82737EGF-like 21; calcium-binding Reviewed predictionAdd
BLAST
Domaini829 – 86739EGF-like 22Add
BLAST
Domaini869 – 90537EGF-like 23; calcium-binding Reviewed predictionAdd
BLAST
Domaini907 – 94337EGF-like 24Add
BLAST
Domaini945 – 98137EGF-like 25; calcium-binding Reviewed predictionAdd
BLAST
Domaini983 – 101937EGF-like 26Add
BLAST
Domaini1021 – 105737EGF-like 27Add
BLAST
Domaini1059 – 109537EGF-like 28Add
BLAST
Domaini1097 – 114347EGF-like 29Add
BLAST
Domaini1145 – 118137EGF-like 30Add
BLAST
Domaini1183 – 121937EGF-like 31; calcium-binding Reviewed predictionAdd
BLAST
Domaini1221 – 126545EGF-like 32; calcium-binding Reviewed predictionAdd
BLAST
Domaini1267 – 130539EGF-like 33Add
BLAST
Domaini1307 – 134640EGF-like 34Add
BLAST
Domaini1348 – 138437EGF-like 35Add
BLAST
Domaini1387 – 142640EGF-like 36Add
BLAST
Repeati1449 – 148941LNR 1Add
BLAST
Repeati1490 – 153142LNR 2Add
BLAST
Repeati1532 – 157140LNR 3Add
BLAST
Repeati1927 – 195630ANK 1Add
BLAST
Repeati1960 – 199031ANK 2Add
BLAST
Repeati1994 – 202330ANK 3Add
BLAST
Repeati2027 – 205630ANK 4Add
BLAST
Repeati2060 – 208930ANK 5Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1947 – 19559HIF1AN-binding By similarity
Regioni2014 – 20229HIF1AN-binding By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1575 – 15784Poly-Val
Compositional biasi1661 – 16644Poly-Arg
Compositional biasi1728 – 17314Poly-Pro
Compositional biasi1740 – 17434Poly-Ala
Compositional biasi1901 – 19044Poly-Glu
Compositional biasi2259 – 22624Poly-Gly
Compositional biasi2403 – 24064Poly-Gln
Compositional biasi2410 – 24178Poly-Pro
Compositional biasi2521 – 25244Poly-Ser

Sequence similaritiesi

Belongs to the NOTCH family.
Contains 5 ANK repeats.
Contains 36 EGF-like domains.

Keywords - Domaini

ANK repeat, EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0666.
HOGENOMiHOG000234369.
HOVERGENiHBG052650.
KOiK02599.
OMAiGASCQNT.
OrthoDBiEOG7992RD.
PhylomeDBiP46531.
TreeFamiTF351641.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR024600. DUF3454_notch.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR008297. Notch.
IPR022362. Notch_1.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF11936. DUF3454. 1 hit.
PF00008. EGF. 23 hits.
PF07645. EGF_CA. 5 hits.
PF12661. hEGF. 1 hit.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view]
PIRSFiPIRSF002279. Notch. 1 hit.
PRINTSiPR01452. LNOTCHREPEAT.
PR01984. NOTCH1.
SMARTiSM00248. ANK. 6 hits.
SM00181. EGF. 12 hits.
SM00179. EGF_CA. 24 hits.
SM00004. NL. 3 hits.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF57184. SSF57184. 6 hits.
SSF90193. SSF90193. 3 hits.
PROSITEiPS50297. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P46531-1 [UniParc]FASTAAdd to Basket

« Hide

MPPLLAPLLC LALLPALAAR GPRCSQPGET CLNGGKCEAA NGTEACVCGG     50
AFVGPRCQDP NPCLSTPCKN AGTCHVVDRR GVADYACSCA LGFSGPLCLT 100
PLDNACLTNP CRNGGTCDLL TLTEYKCRCP PGWSGKSCQQ ADPCASNPCA 150
NGGQCLPFEA SYICHCPPSF HGPTCRQDVN ECGQKPGLCR HGGTCHNEVG 200
SYRCVCRATH TGPNCERPYV PCSPSPCQNG GTCRPTGDVT HECACLPGFT 250
GQNCEENIDD CPGNNCKNGG ACVDGVNTYN CRCPPEWTGQ YCTEDVDECQ 300
LMPNACQNGG TCHNTHGGYN CVCVNGWTGE DCSENIDDCA SAACFHGATC 350
HDRVASFYCE CPHGRTGLLC HLNDACISNP CNEGSNCDTN PVNGKAICTC 400
PSGYTGPACS QDVDECSLGA NPCEHAGKCI NTLGSFECQC LQGYTGPRCE 450
IDVNECVSNP CQNDATCLDQ IGEFQCICMP GYEGVHCEVN TDECASSPCL 500
HNGRCLDKIN EFQCECPTGF TGHLCQYDVD ECASTPCKNG AKCLDGPNTY 550
TCVCTEGYTG THCEVDIDEC DPDPCHYGSC KDGVATFTCL CRPGYTGHHC 600
ETNINECSSQ PCRHGGTCQD RDNAYLCFCL KGTTGPNCEI NLDDCASSPC 650
DSGTCLDKID GYECACEPGY TGSMCNINID ECAGNPCHNG GTCEDGINGF 700
TCRCPEGYHD PTCLSEVNEC NSNPCVHGAC RDSLNGYKCD CDPGWSGTNC 750
DINNNECESN PCVNGGTCKD MTSGYVCTCR EGFSGPNCQT NINECASNPC 800
LNQGTCIDDV AGYKCNCLLP YTGATCEVVL APCAPSPCRN GGECRQSEDY 850
ESFSCVCPTG WQGQTCEVDI NECVLSPCRH GASCQNTHGG YRCHCQAGYS 900
GRNCETDIDD CRPNPCHNGG SCTDGINTAF CDCLPGFRGT FCEEDINECA 950
SDPCRNGANC TDCVDSYTCT CPAGFSGIHC ENNTPDCTES SCFNGGTCVD 1000
GINSFTCLCP PGFTGSYCQH DVNECDSQPC LHGGTCQDGC GSYRCTCPQG 1050
YTGPNCQNLV HWCDSSPCKN GGKCWQTHTQ YRCECPSGWT GLYCDVPSVS 1100
CEVAAQRQGV DVARLCQHGG LCVDAGNTHH CRCQAGYTGS YCEDLVDECS 1150
PSPCQNGATC TDYLGGYSCK CVAGYHGVNC SEEIDECLSH PCQNGGTCLD 1200
LPNTYKCSCP RGTQGVHCEI NVDDCNPPVD PVSRSPKCFN NGTCVDQVGG 1250
YSCTCPPGFV GERCEGDVNE CLSNPCDARG TQNCVQRVND FHCECRAGHT 1300
GRRCESVING CKGKPCKNGG TCAVASNTAR GFICKCPAGF EGATCENDAR 1350
TCGSLRCLNG GTCISGPRSP TCLCLGPFTG PECQFPASSP CLGGNPCYNQ 1400
GTCEPTSESP FYRCLCPAKF NGLLCHILDY SFGGGAGRDI PPPLIEEACE 1450
LPECQEDAGN KVCSLQCNNH ACGWDGGDCS LNFNDPWKNC TQSLQCWKYF 1500
SDGHCDSQCN SAGCLFDGFD CQRAEGQCNP LYDQYCKDHF SDGHCDQGCN 1550
SAECEWDGLD CAEHVPERLA AGTLVVVVLM PPEQLRNSSF HFLRELSRVL 1600
HTNVVFKRDA HGQQMIFPYY GREEELRKHP IKRAAEGWAA PDALLGQVKA 1650
SLLPGGSEGG RRRRELDPMD VRGSIVYLEI DNRQCVQASS QCFQSATDVA 1700
AFLGALASLG SLNIPYKIEA VQSETVEPPP PAQLHFMYVA AAAFVLLFFV 1750
GCGVLLSRKR RRQHGQLWFP EGFKVSEASK KKRREPLGED SVGLKPLKNA 1800
SDGALMDDNQ NEWGDEDLET KKFRFEEPVV LPDLDDQTDH RQWTQQHLDA 1850
ADLRMSAMAP TPPQGEVDAD CMDVNVRGPD GFTPLMIASC SGGGLETGNS 1900
EEEEDAPAVI SDFIYQGASL HNQTDRTGET ALHLAARYSR SDAAKRLLEA 1950
SADANIQDNM GRTPLHAAVS ADAQGVFQIL IRNRATDLDA RMHDGTTPLI 2000
LAARLAVEGM LEDLINSHAD VNAVDDLGKS ALHWAAAVNN VDAAVVLLKN 2050
GANKDMQNNR EETPLFLAAR EGSYETAKVL LDHFANRDIT DHMDRLPRDI 2100
AQERMHHDIV RLLDEYNLVR SPQLHGAPLG GTPTLSPPLC SPNGYLGSLK 2150
PGVQGKKVRK PSSKGLACGS KEAKDLKARR KKSQDGKGCL LDSSGMLSPV 2200
DSLESPHGYL SDVASPPLLP SPFQQSPSVP LNHLPGMPDT HLGIGHLNVA 2250
AKPEMAALGG GGRLAFETGP PRLSHLPVAS GTSTVLGSSS GGALNFTVGG 2300
STSLNGQCEW LSRLQSGMVP NQYNPLRGSV APGPLSTQAP SLQHGMVGPL 2350
HSSLAASALS QMMSYQGLPS TRLATQPHLV QTQQVQPQNL QMQQQNLQPA 2400
NIQQQQSLQP PPPPPQPHLG VSSAASGHLG RSFLSGEPSQ ADVQPLGPSS 2450
LAVHTILPQE SPALPTSLPS SLVPPVTAAQ FLTPPSQHSY SSPVDNTPSH 2500
QLQVPEHPFL TPSPESPDQW SSSSPHSNVS DWSEGVSSPP TSMQSQIARI 2550
PEAFK 2555
Length:2,555
Mass (Da):272,505
Last modified:September 23, 2008 - v4
Checksum:iE173C872D195F028
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti300 – 3001Q → R.
Corresponds to variant rs11574885 [ dbSNP | Ensembl ].
VAR_034898
Natural varianti879 – 8791R → W.
Corresponds to variant rs11574895 [ dbSNP | Ensembl ].
VAR_048990
Natural varianti1671 – 16711V → I.
Corresponds to variant rs2229968 [ dbSNP | Ensembl ].
VAR_046618

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti187 – 1871G → R in AAG33848. 1 Publication
Sequence conflicti187 – 1871G → R in AAA60614. 1 Publication
Sequence conflicti282 – 2821R → P in AAG33848. 1 Publication
Sequence conflicti282 – 2821R → P in AAA60614. 1 Publication
Sequence conflicti477 – 4771I → M in AAG33848. 1 Publication
Sequence conflicti477 – 4771I → M in AAA60614. 1 Publication
Sequence conflicti614 – 6152HG → LR in AAG33848. 1 Publication
Sequence conflicti614 – 6152HG → LR in AAA60614. 1 Publication
Sequence conflicti621 – 6211R → P in AAG33848. 1 Publication
Sequence conflicti621 – 6211R → P in AAA60614. 1 Publication
Sequence conflicti677 – 6771I → S in AAG33848. 1 Publication
Sequence conflicti677 – 6771I → S in AAA60614. 1 Publication
Sequence conflicti775 – 7751Y → I in AAG33848. 1 Publication
Sequence conflicti775 – 7751Y → I in AAA60614. 1 Publication
Sequence conflicti803 – 8031Q → K in AAG33848. 1 Publication
Sequence conflicti803 – 8031Q → K in AAA60614. 1 Publication
Sequence conflicti860 – 8623GWQ → AGAK in AAG33848. 1 Publication
Sequence conflicti860 – 8623GWQ → AGAK in AAA60614. 1 Publication
Sequence conflicti1021 – 10211D → V in AAG33848. 1 Publication
Sequence conflicti1021 – 10211D → V in AAA60614. 1 Publication
Sequence conflicti1028 – 10281Q → R in AAG33848. 1 Publication
Sequence conflicti1028 – 10281Q → R in AAA60614. 1 Publication
Sequence conflicti1032 – 10321H → L in AAG33848. 1 Publication
Sequence conflicti1032 – 10321H → L in AAA60614. 1 Publication
Sequence conflicti1040 – 10434CGSY → RGLH in AAG33848. 1 Publication
Sequence conflicti1040 – 10434CGSY → RGLH in AAA60614. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF308602 mRNA. Translation: AAG33848.1.
AL592301, AL354671 Genomic DNA. Translation: CAI13934.1.
AL354671, AL592301 Genomic DNA. Translation: CAI16149.1.
M73980 mRNA. Translation: AAA60614.1.
AB209873 mRNA. Translation: BAD93110.1.
CCDSiCCDS43905.1.
PIRiA40043.
RefSeqiNP_060087.3. NM_017617.3.
UniGeneiHs.495473.

Genome annotation databases

EnsembliENST00000277541; ENSP00000277541; ENSG00000148400.
GeneIDi4851.
KEGGihsa:4851.
UCSCiuc004chz.3. human.

Polymorphism databases

DMDMi206729936.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF308602 mRNA. Translation: AAG33848.1 .
AL592301 , AL354671 Genomic DNA. Translation: CAI13934.1 .
AL354671 , AL592301 Genomic DNA. Translation: CAI16149.1 .
M73980 mRNA. Translation: AAA60614.1 .
AB209873 mRNA. Translation: BAD93110.1 .
CCDSi CCDS43905.1.
PIRi A40043.
RefSeqi NP_060087.3. NM_017617.3.
UniGenei Hs.495473.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali P46531.
SMRi P46531. Positions 411-526, 1448-1728, 1883-2122.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110913. 179 interactions.
DIPi DIP-29919N.
IntActi P46531. 21 interactions.
MINTi MINT-1417018.
STRINGi 9606.ENSP00000277541.

Chemistry

ChEMBLi CHEMBL2146346.

PTM databases

PhosphoSitei P46531.

Polymorphism databases

DMDMi 206729936.

Proteomic databases

MaxQBi P46531.
PaxDbi P46531.
PRIDEi P46531.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000277541 ; ENSP00000277541 ; ENSG00000148400 .
GeneIDi 4851.
KEGGi hsa:4851.
UCSCi uc004chz.3. human.

Organism-specific databases

CTDi 4851.
GeneCardsi GC09M139388.
H-InvDB HIX0008549.
HGNCi HGNC:7881. NOTCH1.
HPAi CAB008112.
CAB022466.
MIMi 109730. phenotype.
190198. gene.
neXtProti NX_P46531.
Orphaneti 1244. Bicuspid aortic valve.
PharmGKBi PA31683.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0666.
HOGENOMi HOG000234369.
HOVERGENi HBG052650.
KOi K02599.
OMAi GASCQNT.
OrthoDBi EOG7992RD.
PhylomeDBi P46531.
TreeFami TF351641.

Enzyme and pathway databases

Reactomei REACT_118568. Pre-NOTCH Transcription and Translation.
REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_118722. Pre-NOTCH Processing in the Endoplasmic Reticulum.
REACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_118798. Pre-NOTCH Processing in Golgi.
REACT_13673. Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells.
REACT_14835. Notch-HLH transcription pathway.
REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
REACT_160106. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
REACT_160305. Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling.
SignaLinki P46531.

Miscellaneous databases

EvolutionaryTracei P46531.
GeneWikii Notch-1.
GenomeRNAii 4851.
NextBioi 18684.
PROi P46531.
SOURCEi Search...

Gene expression databases

ArrayExpressi P46531.
Bgeei P46531.
CleanExi HS_NOTCH1.
Genevestigatori P46531.

Family and domain databases

Gene3Di 1.25.40.20. 1 hit.
InterProi IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR024600. DUF3454_notch.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR008297. Notch.
IPR022362. Notch_1.
IPR000800. Notch_dom.
IPR010660. Notch_NOD_dom.
IPR011656. Notch_NODP_dom.
[Graphical view ]
Pfami PF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF11936. DUF3454. 1 hit.
PF00008. EGF. 23 hits.
PF07645. EGF_CA. 5 hits.
PF12661. hEGF. 1 hit.
PF06816. NOD. 1 hit.
PF07684. NODP. 1 hit.
PF00066. Notch. 3 hits.
[Graphical view ]
PIRSFi PIRSF002279. Notch. 1 hit.
PRINTSi PR01452. LNOTCHREPEAT.
PR01984. NOTCH1.
SMARTi SM00248. ANK. 6 hits.
SM00181. EGF. 12 hits.
SM00179. EGF_CA. 24 hits.
SM00004. NL. 3 hits.
[Graphical view ]
SUPFAMi SSF48403. SSF48403. 1 hit.
SSF57184. SSF57184. 6 hits.
SSF90193. SSF90193. 3 hits.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Complete human notch 1 (hN1) cDNA sequence."
    Mann R.S., Blaumueller C.M., Zagouras P.
    Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms."
    Ellisen L.W., Bird J., West D.C., Soreng A.L., Reynolds T.C., Smith S.D., Sklar J.
    Cell 66:649-661(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-2443.
  4. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
    Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 489-2555.
    Tissue: Aortic endothelium.
  5. Cited for: PROTEIN SEQUENCE OF 1947-1962, INTERACTION WITH HIF1AN, HYDROXYLATION AT ASN-1955, IDENTIFICATION BY MASS SPECTROMETRY.
  6. Cited for: IDENTIFICATION OF LIGANDS.
  7. Cited for: INTERACTION WITH DTX1.
  8. "SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function."
    Zhou S., Fujimuro M., Hsieh J.J., Chen L., Miyamoto A., Weinmaster G., Hayward S.D.
    Mol. Cell. Biol. 20:2400-2410(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SNW1.
  9. "MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors."
    Wu L., Aster J.C., Blacklow S.C., Lake R., Artavanis-Tsakonas S., Griffin J.D.
    Nat. Genet. 26:484-489(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAML1.
  10. "Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors."
    Wu L., Sun T., Kobayashi K., Gao P., Griffin J.D.
    Mol. Cell. Biol. 22:7688-7700(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAML2 AND MAML3.
  11. "AIP4/Itch regulates Notch receptor degradation in the absence of ligand."
    Chastagner P., Israel A., Brou C.
    PLoS ONE 3:E2735-E2735(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION BY ITCH.
  12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  13. "Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis."
    Brutsch R., Liebler S.S., Wustehube J., Bartol A., Herberich S.E., Adam M.G., Telzerow A., Augustin H.G., Fischer A.
    Circ. Res. 107:592-601(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "Notch1 binds and induces degradation of Snail in hepatocellular carcinoma."
    Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K., Jung G.
    BMC Biol. 9:83-83(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SNAI1 AND MDM2A.
  15. "The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway."
    Gupta-Rossi N., Ortica S., Meas-Yedid V., Heuss S., Moretti J., Olivo-Marin J.C., Israel A.
    J. Biol. Chem. 286:18720-18730(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AAK1.
  16. "Serum- and glucocorticoid-inducible kinase 1 (SGK1) controls Notch1 signaling by downregulation of protein stability through Fbw7 ubiquitin ligase."
    Mo J.S., Ann E.J., Yoon J.H., Jung J., Choi Y.H., Kim H.Y., Ahn J.S., Kim S.M., Kim M.Y., Hong J.A., Seo M.S., Lang F., Choi E.J., Park H.S.
    J. Cell Sci. 124:100-112(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SGK1 AND FBXW7.
  17. Cited for: INTERACTION WITH SNW1.
  18. "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality."
    Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H., Brueckner M., Khokha M.K.
    Nature 504:456-459(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT THR-232; THR-1402 AND THR-1725, PROTEOLYTIC PROCESSING.
  19. "Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1."
    Vardar D., North C.L., Sanchez-Irizarry C., Aster J.C., Blacklow S.C.
    Biochemistry 42:7061-7067(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 1446-1480 IN COMPLEX WITH CALCIUM IONS, DISULFIDE BONDS.
  20. "Structural and functional properties of the human notch-1 ligand binding region."
    Hambleton S., Valeyev N.V., Muranyi A., Knott V., Werner J.M., McMichael A.J., Handford P.A., Downing A.K.
    Structure 12:2173-2183(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 411-526.
  21. "High-resolution crystal structure of the human Notch 1 ankyrin domain."
    Ehebauer M.T., Chirgadze D.Y., Hayward P., Martinez Arias A., Blundell T.L.
    Biochem. J. 392:13-20(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1872-2114.
  22. "Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes."
    Nam Y., Sliz P., Song L., Aster J.C., Blacklow S.C.
    Cell 124:973-983(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 1872-2126 IN COMPLEX WITH RBPSUH AND MAML1.
  23. Cited for: INVOLVEMENT IN AOVD1.

Entry informationi

Entry nameiNOTC1_HUMAN
AccessioniPrimary (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: September 3, 2014
This is version 179 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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