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- PDB-2nb1: P63/p73 hetero-tetramerisation domain -

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Basic information

Entry
Database: PDB / ID: 2nb1
TitleP63/p73 hetero-tetramerisation domain
Components
  • Tumor protein 63Neoplasm
  • Tumor protein p73P73
KeywordsTRANSCRIPTION / p63 / p73 / tetramerization domain / hetero tetramer / transcription factor
Function / homology
Function and homology information


ectoderm and mesoderm interaction / epidermal cell division / cloacal septation / positive regulation of somatic stem cell population maintenance / positive regulation of lung ciliated cell differentiation / prostatic bud formation / negative regulation of mesoderm development / female genitalia morphogenesis / establishment of planar polarity / positive regulation of keratinocyte proliferation ...ectoderm and mesoderm interaction / epidermal cell division / cloacal septation / positive regulation of somatic stem cell population maintenance / positive regulation of lung ciliated cell differentiation / prostatic bud formation / negative regulation of mesoderm development / female genitalia morphogenesis / establishment of planar polarity / positive regulation of keratinocyte proliferation / negative regulation of keratinocyte differentiation / squamous basal epithelial stem cell differentiation involved in prostate gland acinus development / polarized epithelial cell differentiation / negative regulation of intracellular estrogen receptor signaling pathway / proximal/distal pattern formation / negative regulation of cardiac muscle cell proliferation / positive regulation of fibroblast apoptotic process / positive regulation of cell cycle G1/S phase transition / WW domain binding / skin morphogenesis / cranial skeletal system development / sympathetic nervous system development / post-anal tail morphogenesis / embryonic forelimb morphogenesis / embryonic hindlimb morphogenesis / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / Regulation of TP53 Activity through Association with Co-factors / hair follicle morphogenesis / positive regulation of oligodendrocyte differentiation / positive regulation of Notch signaling pathway / regulation of epidermal cell division / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / positive regulation of stem cell proliferation / TP53 Regulates Transcription of Caspase Activators and Caspases / epithelial cell development / odontogenesis of dentin-containing tooth / negative regulation of cellular senescence / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / keratinocyte proliferation / negative regulation of neuron differentiation / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / establishment of skin barrier / mismatch repair / Pyroptosis / positive regulation of osteoblast differentiation / keratinocyte differentiation / MDM2/MDM4 family protein binding / Notch signaling pathway / response to organonitrogen compound / regulation of mitotic cell cycle / transcription corepressor binding / kidney development / skeletal system development / stem cell proliferation / positive regulation of apoptotic signaling pathway / determination of adult lifespan / promoter-specific chromatin binding / TP53 Regulates Metabolic Genes / protein tetramerization / RNA polymerase II transcription regulatory region sequence-specific DNA binding / intrinsic apoptotic signaling pathway in response to DNA damage / cellular senescence / p53 binding / cell junction / RUNX1 regulates transcription of genes involved in differentiation of HSCs / spermatogenesis / regulation of gene expression / DNA-binding transcription activator activity, RNA polymerase II-specific / neuron apoptotic process / DNA-binding transcription factor binding / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / positive regulation of MAPK cascade / damaged DNA binding / transcription cis-regulatory region binding / DNA-binding transcription factor activity, RNA polymerase II-specific / regulation of cell cycle / chromatin remodeling / response to xenobiotic stimulus / positive regulation of apoptotic process / cell cycle / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of cell population proliferation / intracellular membrane-bounded organelle / negative regulation of DNA-templated transcription / apoptotic process / DNA damage response / chromatin binding / dendrite / chromatin / regulation of transcription by RNA polymerase II / protein kinase binding / positive regulation of DNA-templated transcription / Golgi apparatus / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / DNA binding / nucleoplasm
Similarity search - Function
Tumour protein p63, SAM domain / Tumour protein p73, SAM domain / p53 family signature. / p53, tetramerisation domain / P53 tetramerisation motif / p53, DNA-binding domain / P53 DNA-binding domain / p53 tumour suppressor family / p53-like tetramerisation domain superfamily / p53/RUNT-type transcription factor, DNA-binding domain superfamily ...Tumour protein p63, SAM domain / Tumour protein p73, SAM domain / p53 family signature. / p53, tetramerisation domain / P53 tetramerisation motif / p53, DNA-binding domain / P53 DNA-binding domain / p53 tumour suppressor family / p53-like tetramerisation domain superfamily / p53/RUNT-type transcription factor, DNA-binding domain superfamily / SAM domain (Sterile alpha motif) / p53-like transcription factor, DNA-binding / Sterile alpha motif. / Sterile alpha motif domain / Sterile alpha motif/pointed domain superfamily
Similarity search - Domain/homology
Tumor protein p73 / Tumor protein 63
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / molecular dynamics
Model detailsclosest to the average, model1
AuthorsGebel, J. / Buchner, L. / Loehr, F.M. / Luh, L.M. / Coutandin, D. / Guentert, P. / Doetsch, V.
CitationJournal: Cell Death Differ. / Year: 2016
Title: Mechanism of TAp73 inhibition by Delta Np63 and structural basis of p63/p73 hetero-tetramerization.
Authors: Gebel, J. / Luh, L.M. / Coutandin, D. / Osterburg, C. / Lohr, F. / Schafer, B. / Frombach, A.S. / Sumyk, M. / Buchner, L. / Krojer, T. / Salah, E. / Mathea, S. / Guntert, P. / Knapp, S. / Dotsch, V.
History
DepositionJan 19, 2016Deposition site: BMRB / Processing site: RCSB
Revision 1.0Dec 7, 2016Provider: repository / Type: Initial release
Revision 1.1Dec 14, 2016Group: Other
Revision 1.2Nov 22, 2017Group: Database references / Category: pdbx_database_related / Item: _pdbx_database_related.db_id
Revision 1.3Jun 14, 2023Group: Data collection / Database references / Other
Category: database_2 / pdbx_database_status ...database_2 / pdbx_database_status / pdbx_nmr_software / pdbx_nmr_spectrometer / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_nmr_data / _pdbx_nmr_software.name / _pdbx_nmr_spectrometer.model / _struct_ref_seq_dif.details
Revision 1.4May 15, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 / Item: _database_2.pdbx_DOI

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Tumor protein 63
B: Tumor protein p73
C: Tumor protein 63
D: Tumor protein p73


Theoretical massNumber of molelcules
Total (without water)26,7164
Polymers26,7164
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 200target function
RepresentativeModel #1closest to the average

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Components

#1: Protein Tumor protein 63 / Neoplasm / p63 / Chronic ulcerative stomatitis protein / CUSP / Keratinocyte transcription factor KET / ...p63 / Chronic ulcerative stomatitis protein / CUSP / Keratinocyte transcription factor KET / Transformation-related protein 63 / TP63 / Tumor protein p73-like / p73L / p40 / p51


Mass: 7323.190 Da / Num. of mol.: 2
Fragment: Tetramerization domain of 63, UNP residues 397-455
Mutation: K21E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KET, P63, P73H, P73L, TP63, TP73L / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / References: UniProt: Q9H3D4
#2: Protein/peptide Tumor protein p73 / P73 / p53-like transcription factor / p53-related protein


Mass: 6034.894 Da / Num. of mol.: 2
Fragment: Tetramerization domain of p73, UNP residues 351-398
Mutation: E15K
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: P73, TP73 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / References: UniProt: O15350

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1113D HN(CA)CB
1213D HN(CA)CO
1313D 1H-15N NOESY
1423D HN(CA)CB
1523D HN(CA)CO
1623D 1H-15N NOESY
1713D H(CCO)NH
1813D C(CO)NH
1923D H(CCO)NH
11023D C(CO)NH
11112D 1H-13C HSQC aromatic
11222D 1H-13C HSQC aromatic
11312D (H)CB(CG)CCH-TOCSY
11422D (H)CB(CG)CCH-TOCSY
11512D (HB)CB(CDCD)HD
11622D (HB)CB(CDCD)HD
11713D 1H-13C NOESY aromatic
11823D 1H-13C NOESY aromatic
11913D 13C/15N-filtered NOESY-[13C,1H]-HSQC
12023D 13C/15N-filtered NOESY-[13C,1H]-HSQC
12113D 13C/15N-filtered NOESY-[15N,1H]-TROSY
12223D 13C/15N-filtered NOESY-[15N,1H]-TROSY
12313D 1H-13C NOESY
12423D 1H-13C NOESY
12512D 1H-13C HSQC
12622D 1H-13C HSQC
12712D 1H-15N HSQC
12822D 1H-15N HSQC
12952D 1H-15N HSQC
13062D 1H-15N HSQC
13133D lr-HNCO
13243D lr-HNCO
23373D lr-HNCO

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Sample preparation

Details
Solution-IDContentsSolvent system
10.5 mM [U-100% 13C; U-100% 15N] p63 tetramerization domain, 0.5 mM p73 tetramerization domain, 25 mM HEPES, 50 mM sodium chloride, 95% H2O/5% D2O95% H2O/5% D2O
20.5 mM p63 tetramerization domain, 0.5 mM [U-100% 13C; U-100% 15N] p73 tetramerization domain, 25 mM HEPES, 50 mM sodium chloride, 95% H2O/5% D2O95% H2O/5% D2O
30.5 mM [U-100% 15N] p63 tetramerization domain, 0.5 mM [U-100% 13C] p63 tetramerization domain, 1 mM p73 tetramerization domain, 25 mM HEPES, 50 mM sodium chloride, 95% H2O/5% D2O95% H2O/5% D2O
41 mM p63 tetramerization domain, 0.5 mM [U-100% 15N] p73 tetramerization domain, 0.5 mM [U-100% 13C] p73 tetramerization domain, 25 mM HEPES, 50 mM sodium chloride, 95% H2O/5% D2O95% H2O/5% D2O
50.5 mM [U-100% 15N] p63 tetramerization domain, 0.5 mM p73 tetramerization domain, 25 mM HEPES, 50 mM sodium chloride, 100% D2O100% D2O
60.5 mM p63 tetramerization domain, 0.5 mM [U-100% 15N] p73 tetramerization domain, 25 mM HEPES, 50 mM sodium chloride, 100% D2O100% D2O
70.5 mM [U-100% 15N] p63 tetramerization domain, 0.5 mM [U-100% 13C] p63 tetramerization domain, 0.5 mM [U-100% 15N] p73 tetramerization domain, 0.5 mM [U-100% 13C] p73 tetramerization domain, 25 mM HEPES, 50 mM sodium chloride, 95% H2O/5% D2O95% H2O/5% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.5 mMp63 tetramerization domain-1[U-100% 13C; U-100% 15N]1
0.5 mMp73 tetramerization domain-21
25 mMHEPES-31
50 mMsodium chloride-41
0.5 mMp63 tetramerization domain-52
0.5 mMp73 tetramerization domain-6[U-100% 13C; U-100% 15N]2
25 mMHEPES-72
50 mMsodium chloride-82
0.5 mMp63 tetramerization domain-9[U-100% 15N]3
0.5 mMp63 tetramerization domain-10[U-100% 13C]3
1 mMp73 tetramerization domain-113
25 mMHEPES-123
50 mMsodium chloride-133
1 mMp63 tetramerization domain-144
0.5 mMp73 tetramerization domain-15[U-100% 15N]4
0.5 mMp73 tetramerization domain-16[U-100% 13C]4
25 mMHEPES-174
50 mMsodium chloride-184
0.5 mMp63 tetramerization domain-19[U-100% 15N]5
0.5 mMp73 tetramerization domain-205
25 mMHEPES-215
50 mMsodium chloride-225
0.5 mMp63 tetramerization domain-236
0.5 mMp73 tetramerization domain-24[U-100% 15N]6
25 mMHEPES-256
50 mMsodium chloride-266
0.5 mMp63 tetramerization domain-27[U-100% 15N]7
0.5 mMp63 tetramerization domain-28[U-100% 13C]7
0.5 mMp73 tetramerization domain-29[U-100% 15N]7
0.5 mMp73 tetramerization domain-30[U-100% 13C]7
25 mMHEPES-317
50 mMsodium chloride-327
Sample conditions
Conditions-IDIonic strengthpHPressure (kPa)Temperature (K)
175 7 ambient atm310 K
25 6 ambient atm310 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker Avance IIBrukerAVANCE II5001
Bruker AvanceBrukerAVANCE7002
Bruker AvanceBrukerAVANCE8003
Bruker AvanceBrukerAVANCE9004

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Processing

NMR software
NameVersionDeveloperClassification
CYANA3.97Guntert, Mumenthaler and Wuthrichstructure solution
TALOS+Cornilescu, Delaglio and Baxdata analysis
OPALp1.4Luginbuhl, Guntert, Billeter and Wuthrichrefinement
Sparky3.114Goddardpeak picking
Sparky3.114Goddardchemical shift assignment
TopSpin3.2Bruker Biospinprocessing
TopSpin3.2Bruker Biospindata analysis
RefinementMethod: molecular dynamics / Software ordinal: 1
NMR constraintsNOE constraints total: 2582 / NOE intraresidue total count: 412 / NOE long range total count: 850 / NOE medium range total count: 614 / NOE sequential total count: 706 / Hydrogen bond constraints total count: 440 / Protein chi angle constraints total count: 0 / Protein other angle constraints total count: 0 / Protein phi angle constraints total count: 180 / Protein psi angle constraints total count: 180
NMR representativeSelection criteria: closest to the average
NMR ensembleAverage torsion angle constraint violation: 4.96 ° / Conformer selection criteria: target function / Conformers calculated total number: 200 / Conformers submitted total number: 20 / Maximum torsion angle constraint violation: 6.66 ° / Maximum upper distance constraint violation: 0.17 Å
NMR ensemble rmsDistance rms dev: 0.0076 Å

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