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- PDB-9b3g: Human Notch-1 EGFs 21-23 -

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Basic information

Entry
Database: PDB / ID: 9b3g
TitleHuman Notch-1 EGFs 21-23
ComponentsNeurogenic locus notch homolog protein 1
KeywordsSIGNALING PROTEIN / Notch / EGF / Calcium-binding
Function / homology
Function and homology information


Defective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / growth involved in heart morphogenesis / regulation of cardioblast proliferation / mesenchymal cell development / cell differentiation in spinal cord / venous endothelial cell differentiation / arterial endothelial cell differentiation / collecting duct development ...Defective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / growth involved in heart morphogenesis / regulation of cardioblast proliferation / mesenchymal cell development / cell differentiation in spinal cord / venous endothelial cell differentiation / arterial endothelial cell differentiation / collecting duct development / cell migration involved in endocardial cushion formation / negative regulation of pro-B cell differentiation / Pre-NOTCH Processing in the Endoplasmic Reticulum / mitral valve formation / : / endocardium morphogenesis / distal tubule development / MAML1-RBP-Jkappa- ICN1 complex / cardiac chamber formation / cardiac atrium morphogenesis / pericardium morphogenesis / atrioventricular node development / cardiac ventricle morphogenesis / positive regulation of transcription of Notch receptor target / negative regulation of endothelial cell chemotaxis / cardiac septum morphogenesis / glomerular mesangial cell development / cellular response to tumor cell / positive regulation of smooth muscle cell differentiation / vasculogenesis involved in coronary vascular morphogenesis / negative regulation of extracellular matrix constituent secretion / regulation of extracellular matrix assembly / chemical synaptic transmission, postsynaptic / positive regulation of apoptotic process involved in morphogenesis / endocardial cell differentiation / left/right axis specification / epithelial to mesenchymal transition involved in endocardial cushion formation / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / positive regulation of endothelial cell differentiation / cardiac left ventricle morphogenesis / negative regulation of myotube differentiation / coronary vein morphogenesis / negative regulation of glial cell proliferation / cardiac vascular smooth muscle cell development / neuronal stem cell population maintenance / endocardium development / positive regulation of astrocyte differentiation / cardiac muscle cell myoblast differentiation / negative regulation of cell adhesion molecule production / negative regulation of stem cell differentiation / tissue regeneration / T-helper 17 type immune response / positive regulation of cardiac epithelial to mesenchymal transition / cardiac epithelial to mesenchymal transition / heart trabecula morphogenesis / negative regulation of oligodendrocyte differentiation / regulation of cell adhesion involved in heart morphogenesis / interleukin-17-mediated signaling pathway / Pre-NOTCH Processing in Golgi / negative regulation of catalytic activity / negative regulation of myoblast differentiation / cellular response to follicle-stimulating hormone stimulus / negative regulation of collagen biosynthetic process / negative regulation of cardiac muscle hypertrophy / luteolysis / determination of left/right symmetry / pulmonary valve morphogenesis / tube formation / cardiac muscle tissue morphogenesis / oligodendrocyte differentiation / atrioventricular valve morphogenesis / ventricular trabecula myocardium morphogenesis / coronary artery morphogenesis / negative regulation of cell migration involved in sprouting angiogenesis / negative regulation of cell-cell adhesion mediated by cadherin / negative regulation of ossification / negative regulation of biomineral tissue development / response to muramyl dipeptide / astrocyte differentiation / positive regulation of BMP signaling pathway / endocardial cushion morphogenesis / transcription regulator activator activity / homeostasis of number of cells within a tissue / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / RUNX3 regulates NOTCH signaling / Notch binding / Regulation of NFE2L2 gene expression / NOTCH4 Intracellular Domain Regulates Transcription / positive regulation of neuroblast proliferation / aortic valve morphogenesis / negative regulation of cold-induced thermogenesis / negative regulation of neuron differentiation / NOTCH3 Intracellular Domain Regulates Transcription / NFE2L2 regulating tumorigenic genes / heart looping / ventricular septum morphogenesis / Notch-HLH transcription pathway / Formation of paraxial mesoderm / Somitogenesis
Similarity search - Function
Neurogenic locus notch homolog protein 1 / Notch, C-terminal / Domain of unknown function / : / Notch / Notch, NOD domain / Notch, NODP domain / NOTCH protein / NOTCH protein / NOD ...Neurogenic locus notch homolog protein 1 / Notch, C-terminal / Domain of unknown function / : / Notch / Notch, NOD domain / Notch, NODP domain / NOTCH protein / NOTCH protein / NOD / NODP / Notch-like domain superfamily / LNR (Lin-12/Notch) repeat profile. / LNR domain / Notch domain / Domain found in Notch and Lin-12 / EGF-like, conserved site / Human growth factor-like EGF / : / Calcium-binding EGF domain / EGF-like domain / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like domain / Epidermal growth factor-like domain. / Ankyrin repeat / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 1. / EGF-like domain signature 2. / EGF-like domain / Ankyrin repeat profile. / Ankyrin repeats (3 copies) / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily
Similarity search - Domain/homology
: / Neurogenic locus notch homolog protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / SAD / Resolution: 1.55 Å
AuthorsJohnson, S. / Sheppard, D. / Handford, P.A. / Lea, S.M.
Funding support United Kingdom, 3items
OrganizationGrant numberCountry
Medical Research Council (MRC, United Kingdom)MR/R009317/1 United Kingdom
Medical Research Council (MRC, United Kingdom)MR/V008935/1 United Kingdom
Wellcome Trust100298 United Kingdom
CitationJournal: Structure / Year: 2024
Title: Structural and functional studies of the EGF20-27 region reveal new features of the human Notch receptor important for optimal activation.
Authors: Bo, Z. / Rowntree, T. / Johnson, S. / Nurmahdi, H. / Suckling, R.J. / Hill, J. / Korona, B. / Weisshuhn, P.C. / Sheppard, D. / Meng, Y. / Liang, S. / Lowe, E.D. / Lea, S.M. / Redfield, C. / Handford, P.A.
History
DepositionMar 19, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 16, 2024Provider: repository / Type: Initial release
Revision 1.1Nov 20, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Dec 18, 2024Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Neurogenic locus notch homolog protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)12,8052
Polymers12,6681
Non-polymers1371
Water1,67593
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)41.920, 41.920, 61.180
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number76
Space group name H-MP41
Space group name HallP4w
Symmetry operation#1: x,y,z
#2: -y,x,z+1/4
#3: y,-x,z+3/4
#4: -x,-y,z+1/2

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Components

#1: Protein Neurogenic locus notch homolog protein 1 / Notch 1 / hN1 / Translocation-associated notch protein TAN-1


Mass: 12668.015 Da / Num. of mol.: 1 / Fragment: Human Notch1 EGF domains 21-23
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NOTCH1, TAN1 / Production host: Escherichia coli (E. coli) / References: UniProt: P46531
#2: Chemical ChemComp-BA / BARIUM ION


Mass: 137.327 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ba
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 93 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.12 Å3/Da / Density % sol: 42.03 %
Crystal growTemperature: 294 K / Method: vapor diffusion, sitting drop
Details: 0.2 M Ammonium acetate 0.1 M BIS-Tris pH 5.5 25% (w/v) PEG3350

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.92 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Jul 14, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.92 Å / Relative weight: 1
ReflectionResolution: 1.55→41.92 Å / Num. obs: 15359 / % possible obs: 99.7 % / Redundancy: 4.7 % / Biso Wilson estimate: 25.81 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.022 / Net I/σ(I): 27.1
Reflection shellResolution: 1.55→1.59 Å / Rmerge(I) obs: 0.497 / Mean I/σ(I) obs: 2.5 / Num. unique obs: 1109 / CC1/2: 0.834

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Processing

Software
NameVersionClassification
PHENIX1.21_5207refinement
xia2data reduction
xia2data scaling
AutoSol1.18.2_3874phasing
RefinementMethod to determine structure: SAD / Resolution: 1.55→41.92 Å / SU ML: 0.1806 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 27.8951
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2183 767 4.99 %
Rwork0.195 27740 -
obs0.1961 15331 96.68 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 46.02 Å2
Refinement stepCycle: LAST / Resolution: 1.55→41.92 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms828 0 1 93 922
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.005861
X-RAY DIFFRACTIONf_angle_d0.68381174
X-RAY DIFFRACTIONf_chiral_restr0.0468123
X-RAY DIFFRACTIONf_plane_restr0.0054163
X-RAY DIFFRACTIONf_dihedral_angle_d13.056313
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.55-1.610.36541390.31532759X-RAY DIFFRACTION96.28
1.61-1.670.28071560.28382775X-RAY DIFFRACTION97.25
1.67-1.750.27311480.25142794X-RAY DIFFRACTION96.52
1.75-1.840.25081660.24452741X-RAY DIFFRACTION96.71
1.84-1.950.29311320.242719X-RAY DIFFRACTION94.97
1.95-2.10.26371570.21922722X-RAY DIFFRACTION95.36
2.1-2.310.22761570.22662779X-RAY DIFFRACTION96.29
2.32-2.650.20991430.2042833X-RAY DIFFRACTION98.54
2.65-3.340.2371340.20182808X-RAY DIFFRACTION98.2
3.34-41.920.16931260.15282810X-RAY DIFFRACTION96.64
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
13.76196682487-2.64354550929-0.8453839589433.38158254530.2105064060615.842506457980.0211254947806-0.4763358404441.09730200299-0.08112636906860.04033979067780.742806138661-1.03105412285-0.635933914181-0.06300681533360.3939595567590.0875904190605-0.0196205481760.376442977505-0.05225724247350.731888805558-20.580520821733.170469241726.6796681577
29.40512735549-4.78405693159-0.5768962799230.24312272568-0.0486964652231-0.3413782198250.0680602536419-0.2462469195610.3884974956210.0144690469166-0.00497333503789-0.07130062841370.0158946870132-0.0668060339026-0.04517962271830.2899834115950.020863349629-0.03996086233050.392774807288-0.0805552059960.5779367827338.5409263798321.273272943524.654273649
36.502659241710.739399896177-0.3733854901616.41704525387-0.8267391143559.72051669268-0.332958940657-0.566441999365-0.4599628629340.1076188283210.1853733454880.07571905623010.530404311840.3820404791430.130415530180.3148086158230.08559753931370.04462362999030.3151080630480.003987110078380.21737209017133.36278848137.3555510169326.251758859
44.09755111158-4.111548347090.3272712547349.558697335650.6629058481144.892719847570.724993849508-0.285239893566-0.6691163578570.177409856026-0.370895987872-0.6585997721261.879849008670.726186245417-0.2745620374220.871737636230.218664887551-0.07568712232750.6166730500280.1224753620210.41377279794535.42405391760.83304118115232.5840629608
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11chain 'A' and (resid 794 through 821 )794 - 8211 - 28
22chain 'A' and (resid 822 through 876 )822 - 87629 - 83
33chain 'A' and (resid 877 through 895 )877 - 89584 - 102
44chain 'A' and (resid 896 through 906 )896 - 906103 - 113

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