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P46531

- NOTC1_HUMAN

UniProt

P46531 - NOTC1_HUMAN

Protein

Neurogenic locus notch homolog protein 1

Gene

NOTCH1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 180 (01 Oct 2014)
      Sequence version 4 (23 Sep 2008)
      Previous versions | rss
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    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 proteaseBy similarity
    Sitei1710 – 17112Cleavage; by ADAM17By 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

    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

    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

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Organism-specific databases

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

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 25552537Neurogenic locus notch homolog protein 1PRO_0000007674Add
    BLAST
    Chaini1721 – 2555835Notch 1 extracellular truncationBy similarityPRO_0000007675Add
    BLAST
    Chaini1754 – 2555802Notch 1 intracellular domainBy similarityPRO_0000007676Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi24 ↔ 37By similarity
    Disulfide bondi31 ↔ 46By similarity
    Glycosylationi41 – 411N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi48 ↔ 57By similarity
    Disulfide bondi63 ↔ 74By similarity
    Glycosylationi65 – 651O-linked (Glc...)By similarity
    Disulfide bondi68 ↔ 87By similarity
    Glycosylationi73 – 731O-linked (Fuc...)By similarity
    Disulfide bondi89 ↔ 98By similarity
    Disulfide bondi106 ↔ 117By similarity
    Disulfide bondi111 ↔ 127By similarity
    Glycosylationi116 – 1161O-linked (Fuc...)By similarity
    Disulfide bondi129 ↔ 138By similarity
    Disulfide bondi144 ↔ 155By similarity
    Glycosylationi146 – 1461O-linked (Glc...)By similarity
    Disulfide bondi149 ↔ 164By similarity
    Disulfide bondi166 ↔ 175By similarity
    Disulfide bondi182 ↔ 195By similarity
    Disulfide bondi189 ↔ 204By similarity
    Glycosylationi194 – 1941O-linked (Fuc...)By similarity
    Disulfide bondi206 ↔ 215By similarity
    Disulfide bondi222 ↔ 233By similarity
    Disulfide bondi227 ↔ 243By similarity
    Glycosylationi232 – 2321O-linked (Fuc...); alternate1 Publication
    Glycosylationi232 – 2321O-linked (GalNAc...); alternate1 Publication
    Disulfide bondi245 ↔ 254By similarity
    Disulfide bondi261 ↔ 272By similarity
    Disulfide bondi266 ↔ 281By similarity
    Disulfide bondi283 ↔ 292By similarity
    Disulfide bondi299 ↔ 312By similarity
    Disulfide bondi306 ↔ 321By similarity
    Disulfide bondi323 ↔ 332By similarity
    Disulfide bondi339 ↔ 350By similarity
    Glycosylationi341 – 3411O-linked (Glc...)By similarity
    Disulfide bondi344 ↔ 359By similarity
    Disulfide bondi361 ↔ 370By similarity
    Disulfide bondi376 ↔ 387By similarity
    Glycosylationi378 – 3781O-linked (Glc...)By similarity
    Disulfide bondi381 ↔ 398By similarity
    Disulfide bondi400 ↔ 409By similarity
    Disulfide bondi416 ↔ 429By similarity
    Disulfide bondi423 ↔ 438By similarity
    Disulfide bondi440 ↔ 449By similarity
    Disulfide bondi456 ↔ 467By similarity
    Glycosylationi458 – 4581O-linked (Glc...)By similarity
    Disulfide bondi461 ↔ 476By similarity
    Glycosylationi466 – 4661O-linked (Fuc...)By similarity
    Disulfide bondi478 ↔ 487By similarity
    Disulfide bondi494 ↔ 505By similarity
    Glycosylationi496 – 4961O-linked (Glc...)By similarity
    Disulfide bondi499 ↔ 514By similarity
    Disulfide bondi516 ↔ 525By similarity
    Disulfide bondi532 ↔ 543By similarity
    Glycosylationi534 – 5341O-linked (Glc...)By similarity
    Disulfide bondi537 ↔ 552By similarity
    Disulfide bondi554 ↔ 563By similarity
    Disulfide bondi570 ↔ 580By similarity
    Disulfide bondi575 ↔ 589By similarity
    Disulfide bondi591 ↔ 600By similarity
    Disulfide bondi607 ↔ 618By similarity
    Glycosylationi609 – 6091O-linked (Glc...)By similarity
    Disulfide bondi612 ↔ 627By similarity
    Disulfide bondi629 ↔ 638By similarity
    Disulfide bondi645 ↔ 655By similarity
    Glycosylationi647 – 6471O-linked (Glc...)By similarity
    Disulfide bondi650 ↔ 664By similarity
    Disulfide bondi666 ↔ 675By similarity
    Disulfide bondi682 ↔ 693By similarity
    Disulfide bondi687 ↔ 702By similarity
    Disulfide bondi704 ↔ 713By similarity
    Disulfide bondi720 ↔ 730By similarity
    Glycosylationi722 – 7221O-linked (Glc...)By similarity
    Disulfide bondi725 ↔ 739By similarity
    Disulfide bondi741 ↔ 750By similarity
    Disulfide bondi757 ↔ 768By similarity
    Glycosylationi759 – 7591O-linked (Glc...)By similarity
    Disulfide bondi762 ↔ 777By similarity
    Glycosylationi767 – 7671O-linked (Fuc...)By similarity
    Disulfide bondi779 ↔ 788By similarity
    Disulfide bondi795 ↔ 806By similarity
    Glycosylationi797 – 7971O-linked (Glc...)By similarity
    Disulfide bondi800 ↔ 815By similarity
    Glycosylationi805 – 8051O-linked (Fuc...)By similarity
    Disulfide bondi817 ↔ 826By similarity
    Disulfide bondi833 ↔ 844By similarity
    Disulfide bondi838 ↔ 855By similarity
    Disulfide bondi857 ↔ 866By similarity
    Disulfide bondi873 ↔ 884By similarity
    Disulfide bondi878 ↔ 893By similarity
    Disulfide bondi895 ↔ 904By similarity
    Disulfide bondi911 ↔ 922By similarity
    Disulfide bondi916 ↔ 931By similarity
    Disulfide bondi933 ↔ 942By similarity
    Disulfide bondi949 ↔ 960By similarity
    Glycosylationi951 – 9511O-linked (Glc...)By similarity
    Disulfide bondi954 ↔ 969By similarity
    Glycosylationi959 – 9591N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi971 ↔ 980By similarity
    Disulfide bondi987 ↔ 998By similarity
    Disulfide bondi992 ↔ 1007By similarity
    Disulfide bondi1009 ↔ 1018By similarity
    Disulfide bondi1025 ↔ 1036By similarity
    Glycosylationi1027 – 10271O-linked (Glc...)By similarity
    Disulfide bondi1030 ↔ 1045By similarity
    Glycosylationi1035 – 10351O-linked (Fuc...)By similarity
    Disulfide bondi1047 ↔ 1056By similarity
    Disulfide bondi1063 ↔ 1074By similarity
    Glycosylationi1065 – 10651O-linked (Glc...)By similarity
    Disulfide bondi1068 ↔ 1083By similarity
    Disulfide bondi1085 ↔ 1094By similarity
    Disulfide bondi1101 ↔ 1122By similarity
    Disulfide bondi1116 ↔ 1131By similarity
    Disulfide bondi1133 ↔ 1142By similarity
    Disulfide bondi1149 ↔ 1160By similarity
    Disulfide bondi1154 ↔ 1169By similarity
    Disulfide bondi1171 ↔ 1180By similarity
    Glycosylationi1179 – 11791N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1187 ↔ 1198By similarity
    Glycosylationi1189 – 11891O-linked (Glc...)By similarity
    Disulfide bondi1192 ↔ 1207By similarity
    Glycosylationi1197 – 11971O-linked (Fuc...)By similarity
    Disulfide bondi1209 ↔ 1218By similarity
    Disulfide bondi1225 ↔ 1244By similarity
    Disulfide bondi1238 ↔ 1253By similarity
    Glycosylationi1241 – 12411N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1255 ↔ 1264By similarity
    Disulfide bondi1271 ↔ 1284By similarity
    Glycosylationi1273 – 12731O-linked (Glc...)By similarity
    Disulfide bondi1276 ↔ 1293By similarity
    Disulfide bondi1295 ↔ 1304By similarity
    Disulfide bondi1311 ↔ 1322By similarity
    Disulfide bondi1316 ↔ 1334By similarity
    Disulfide bondi1336 ↔ 1345By similarity
    Disulfide bondi1352 ↔ 1363By similarity
    Disulfide bondi1357 ↔ 1372By similarity
    Glycosylationi1362 – 13621O-linked (Fuc...)By similarity
    Disulfide bondi1374 ↔ 1383By similarity
    Disulfide bondi1391 ↔ 1403By similarity
    Disulfide bondi1397 ↔ 1414By similarity
    Glycosylationi1402 – 14021O-linked (Fuc...); alternate1 Publication
    Glycosylationi1402 – 14021O-linked (GalNAc...); alternate1 Publication
    Disulfide bondi1416 ↔ 1425By similarity
    Disulfide bondi1449 ↔ 14721 Publication
    Disulfide bondi1454 ↔ 14671 Publication
    Disulfide bondi1463 ↔ 14791 Publication
    Glycosylationi1489 – 14891N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1490 ↔ 1514By similarity
    Disulfide bondi1496 ↔ 1509By similarity
    Disulfide bondi1505 ↔ 1521By similarity
    Disulfide bondi1536 ↔ 1549By similarity
    Disulfide bondi1545 ↔ 1561By similarity
    Glycosylationi1587 – 15871N-linked (GlcNAc...)Sequence Analysis
    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 HIF1ANBy 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.By similarity
    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.2 Publications
    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.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.By similarity

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP46531.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini19 – 17351717ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1757 – 2555799CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1736 – 175621HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini20 – 5839EGF-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini59 – 9941EGF-like 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini102 – 13938EGF-like 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini140 – 17637EGF-like 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini178 – 21639EGF-like 5; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini218 – 25538EGF-like 6PROSITE-ProRule annotationAdd
    BLAST
    Domaini257 – 29337EGF-like 7; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini295 – 33339EGF-like 8; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini335 – 37137EGF-like 9; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini372 – 41039EGF-like 10PROSITE-ProRule annotationAdd
    BLAST
    Domaini412 – 45039EGF-like 11; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini452 – 48837EGF-like 12; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini490 – 52637EGF-like 13; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini528 – 56437EGF-like 14; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini566 – 60136EGF-like 15; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini603 – 63937EGF-like 16; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini641 – 67636EGF-like 17; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini678 – 71437EGF-like 18; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini716 – 75136EGF-like 19; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini753 – 78937EGF-like 20PROSITE-ProRule annotationAdd
    BLAST
    Domaini791 – 82737EGF-like 21; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini829 – 86739EGF-like 22PROSITE-ProRule annotationAdd
    BLAST
    Domaini869 – 90537EGF-like 23; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini907 – 94337EGF-like 24PROSITE-ProRule annotationAdd
    BLAST
    Domaini945 – 98137EGF-like 25; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini983 – 101937EGF-like 26PROSITE-ProRule annotationAdd
    BLAST
    Domaini1021 – 105737EGF-like 27PROSITE-ProRule annotationAdd
    BLAST
    Domaini1059 – 109537EGF-like 28PROSITE-ProRule annotationAdd
    BLAST
    Domaini1097 – 114347EGF-like 29PROSITE-ProRule annotationAdd
    BLAST
    Domaini1145 – 118137EGF-like 30PROSITE-ProRule annotationAdd
    BLAST
    Domaini1183 – 121937EGF-like 31; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini1221 – 126545EGF-like 32; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST
    Domaini1267 – 130539EGF-like 33PROSITE-ProRule annotationAdd
    BLAST
    Domaini1307 – 134640EGF-like 34PROSITE-ProRule annotationAdd
    BLAST
    Domaini1348 – 138437EGF-like 35PROSITE-ProRule annotationAdd
    BLAST
    Domaini1387 – 142640EGF-like 36PROSITE-ProRule annotationAdd
    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-bindingBy similarity
    Regioni2014 – 20229HIF1AN-bindingBy 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.Curated
    Contains 5 ANK repeats.PROSITE-ProRule annotation
    Contains 36 EGF-like domains.PROSITE-ProRule annotation
    Contains 3 LNR (Lin/Notch) repeats.PROSITE-ProRule annotation

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti187 – 1871G → R in AAG33848. 1 PublicationCurated
    Sequence conflicti187 – 1871G → R in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti282 – 2821R → P in AAG33848. 1 PublicationCurated
    Sequence conflicti282 – 2821R → P in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti477 – 4771I → M in AAG33848. 1 PublicationCurated
    Sequence conflicti477 – 4771I → M in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti614 – 6152HG → LR in AAG33848. 1 PublicationCurated
    Sequence conflicti614 – 6152HG → LR in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti621 – 6211R → P in AAG33848. 1 PublicationCurated
    Sequence conflicti621 – 6211R → P in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti677 – 6771I → S in AAG33848. 1 PublicationCurated
    Sequence conflicti677 – 6771I → S in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti775 – 7751Y → I in AAG33848. 1 PublicationCurated
    Sequence conflicti775 – 7751Y → I in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti803 – 8031Q → K in AAG33848. 1 PublicationCurated
    Sequence conflicti803 – 8031Q → K in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti860 – 8623GWQ → AGAK in AAG33848. 1 PublicationCurated
    Sequence conflicti860 – 8623GWQ → AGAK in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti1021 – 10211D → V in AAG33848. 1 PublicationCurated
    Sequence conflicti1021 – 10211D → V in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti1028 – 10281Q → R in AAG33848. 1 PublicationCurated
    Sequence conflicti1028 – 10281Q → R in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti1032 – 10321H → L in AAG33848. 1 PublicationCurated
    Sequence conflicti1032 – 10321H → L in AAA60614. (PubMed:1831692)Curated
    Sequence conflicti1040 – 10434CGSY → RGLH in AAG33848. 1 PublicationCurated
    Sequence conflicti1040 – 10434CGSY → RGLH in AAA60614. (PubMed:1831692)Curated

    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 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

    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: October 1, 2014
    This is version 180 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