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- PDB-9xza: E3 ubiquitin-protein ligase CBL-B Apo form -

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Basic information

Entry
Database: PDB / ID: 9xza
TitleE3 ubiquitin-protein ligase CBL-B Apo form
ComponentsE3 ubiquitin-protein ligase CBL-B
KeywordsLIGASE / E3 ubiquitin-protein ligase
Function / homology
Function and homology information


regulation of platelet-derived growth factor receptor-alpha signaling pathway / NLS-bearing protein import into nucleus / negative regulation of T cell activation / negative regulation of epidermal growth factor receptor signaling pathway / negative regulation of T cell receptor signaling pathway / phosphotyrosine residue binding / protein K63-linked ubiquitination / receptor tyrosine kinase binding / RING-type E3 ubiquitin transferase / ubiquitin protein ligase activity ...regulation of platelet-derived growth factor receptor-alpha signaling pathway / NLS-bearing protein import into nucleus / negative regulation of T cell activation / negative regulation of epidermal growth factor receptor signaling pathway / negative regulation of T cell receptor signaling pathway / phosphotyrosine residue binding / protein K63-linked ubiquitination / receptor tyrosine kinase binding / RING-type E3 ubiquitin transferase / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / cell surface receptor signaling pathway / protein stabilization / membrane raft / calcium ion binding / signal transduction / zinc ion binding / plasma membrane / cytosol
Similarity search - Function
E3 ubiquitin-protein ligase CBL-B, RING finger, HC subclass / Adaptor protein Cbl, N-terminal helical / Adaptor protein Cbl, EF hand-like / Adaptor protein Cbl, SH2-like domain / Adaptor protein Cbl, PTB domain / Adaptor protein Cbl / CBL proto-oncogene N-terminal domain 1 / CBL proto-oncogene N-terminus, EF hand-like domain / CBL proto-oncogene N-terminus, SH2-like domain / Cbl-type phosphotyrosine-binding (Cbl-PTB) domain profile. ...E3 ubiquitin-protein ligase CBL-B, RING finger, HC subclass / Adaptor protein Cbl, N-terminal helical / Adaptor protein Cbl, EF hand-like / Adaptor protein Cbl, SH2-like domain / Adaptor protein Cbl, PTB domain / Adaptor protein Cbl / CBL proto-oncogene N-terminal domain 1 / CBL proto-oncogene N-terminus, EF hand-like domain / CBL proto-oncogene N-terminus, SH2-like domain / Cbl-type phosphotyrosine-binding (Cbl-PTB) domain profile. / Adaptor protein Cbl, N-terminal domain superfamily / Ubiquitin associated domain / Ubiquitin-associated domain / Ubiquitin-associated domain (UBA) profile. / Zinc finger, C3HC4 RING-type / Zinc finger, C3HC4 type (RING finger) / Zinc finger, RING-type, conserved site / Zinc finger RING-type signature. / Ring finger / SH2 domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / EF-hand domain pair / Zinc finger, RING/FYVE/PHD-type
Similarity search - Domain/homology
E3 ubiquitin-protein ligase CBL-B
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsGajewski, S. / Clifton, M.C.
Funding support United States, 1items
OrganizationGrant numberCountry
Other private United States
CitationJournal: To Be Published
Title: Discovery and characterization of Cbl-b intra-molecular inhibitory glues with biological activity.
Authors: Gajewski, S.
History
DepositionAug 27, 2025Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 2, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: E3 ubiquitin-protein ligase CBL-B
B: E3 ubiquitin-protein ligase CBL-B
C: E3 ubiquitin-protein ligase CBL-B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)137,07914
Polymers136,3743
Non-polymers70511
Water30617
1
A: E3 ubiquitin-protein ligase CBL-B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,6294
Polymers45,4581
Non-polymers1713
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: E3 ubiquitin-protein ligase CBL-B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,7255
Polymers45,4581
Non-polymers2674
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3
C: E3 ubiquitin-protein ligase CBL-B
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,7255
Polymers45,4581
Non-polymers2674
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)101.760, 101.760, 104.550
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number144
Space group name H-MP31
Space group name HallP31
Symmetry operation#1: x,y,z
#2: -y,x-y,z+1/3
#3: -x+y,-x,z+2/3
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails (eV)
d_1ens_1(chain "A" and (resid 43 through 47 or (resid 48...
d_2ens_1(chain "B" and ((resid 43 through 44 and (name N...
d_3ens_1(chain "C" and ((resid 43 through 44 and (name N...

NCS domain segments:

Ens-ID: ens_1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11ARGARGTRPTRPAA43 - 508 - 15
d_12LEULEULYSLYSAA52 - 6817 - 33
d_13SERSERTYRTYRAA70 - 8235 - 47
d_14HISHISMETMETAA84 - 11549 - 80
d_15LYSLYSARGARGAA117 - 13182 - 96
d_16TYRTYRARGARGAA133 - 14098 - 105
d_17ASNASNTHRTHRAA142 - 278107 - 243
d_18PROPROTHRTHRAA280 - 369245 - 334
d_19GLNGLNALAALAAA371 - 377336 - 342
d_110ASNASNCYSCYSAA379 - 413344 - 378
d_111ILEILEILEILEAA415 - 422380 - 387
d_112CACACACAAD600
d_113ZNZNZNZNAE601
d_21ARGARGTRPTRPBB43 - 508 - 15
d_22LEULEULYSLYSBB52 - 6817 - 33
d_23SERSERTYRTYRBB70 - 8235 - 47
d_24HISHISASPASPBB84 - 9349 - 58
d_25LEULEUMETMETBB98 - 11563 - 80
d_26LYSLYSARGARGBB117 - 13182 - 96
d_27TYRTYRARGARGBB133 - 14098 - 105
d_28ASNASNTHRTHRBB142 - 278107 - 243
d_29PROPROGLYGLYBB280 - 343245 - 308
d_210ILEILETHRTHRBB353 - 369318 - 334
d_211GLNGLNALAALABB371 - 377336 - 342
d_212ASNASNCYSCYSBB379 - 413344 - 378
d_213ILEILEILEILEBB415 - 422380 - 387
d_214CACACACABG501
d_215ZNZNZNZNBH502
d_31ARGARGTRPTRPCC43 - 508 - 15
d_32LEULEULYSLYSCC52 - 6817 - 33
d_33SERSERTYRTYRCC70 - 8235 - 47
d_34HISHISASPASPCC84 - 9349 - 58
d_35LEULEUMETMETCC98 - 11563 - 80
d_36LYSLYSARGARGCC117 - 13182 - 96
d_37TYRTYRARGARGCC133 - 14098 - 105
d_38ASNASNTHRTHRCC142 - 278107 - 243
d_39PROPROGLYGLYCC280 - 343245 - 308
d_310ILEILETHRTHRCC353 - 369318 - 334
d_311GLNGLNALAALACC371 - 377336 - 342
d_312ASNASNCYSCYSCC379 - 413344 - 378
d_313ILEILEILEILECC415 - 422380 - 387
d_314CACACACACK501
d_315ZNZNZNZNCL502

NCS oper:
IDCodeMatrixVector
1given(-0.999392567342, -0.0202577027793, -0.0283570418146), (-0.0200995620372, 0.999780864007, -0.00585077532889), (0.0284693510337, -0.00527725725574, -0.999580735412)-49.7458118845, -29.8921842324, -25.9682825188
2given(0.980372630492, 0.197039620503, 0.00670024880927), (-0.197108863515, 0.980307638571, 0.0120428270207), (-0.00419539102211, -0.0131271364329, 0.999905033982)-11.4519046554, -57.8703949873, 5.54188457097

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Components

#1: Protein E3 ubiquitin-protein ligase CBL-B / Casitas B-lineage lymphoma proto-oncogene b / RING finger protein 56 / RING-type E3 ubiquitin ...Casitas B-lineage lymphoma proto-oncogene b / RING finger protein 56 / RING-type E3 ubiquitin transferase CBL-B / SH3-binding protein CBL-B / Signal transduction protein CBL-B


Mass: 45458.008 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CBLB, RNF56, Nbla00127 / Production host: Escherichia coli (E. coli)
References: UniProt: Q13191, RING-type E3 ubiquitin transferase
#2: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Ca
#3: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Zn
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 17 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationN

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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: 2.29 Å3/Da / Density % sol: 46.33 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 40 mM MOPS, 60 mM HEPES-Na, 30 mM MgCl2, 30 mM CaCl2, 8.4% PEG 8000, 15% ethylene glycol

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.9795 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 16, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.3→14.73 Å / Num. obs: 51530 / % possible obs: 95.7 % / Redundancy: 2.7 % / Biso Wilson estimate: 35.03 Å2 / Rpim(I) all: 0.06217 / Net I/σ(I): 9.9
Reflection shellResolution: 2.3→2.38 Å / Num. unique obs: 5276 / Rpim(I) all: 0.8461

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Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→14.73 Å / Cross valid method: FREE R-VALUE / σ(F): 2.52 / Phase error: 39.6913
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2294 2634 5.11 %
Rwork0.1783 48870 -
obs0.1901 51504 96.06 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 50.34 Å2
Refinement stepCycle: LAST / Resolution: 2.3→14.73 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8631 0 19 17 8667
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00228861
X-RAY DIFFRACTIONf_angle_d0.499412046
X-RAY DIFFRACTIONf_chiral_restr0.03911342
X-RAY DIFFRACTIONf_plane_restr0.00351531
X-RAY DIFFRACTIONf_dihedral_angle_d15.34343101
Refine LS restraints NCS
Ens-IDDom-IDAsym-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2AAX-RAY DIFFRACTIONTorsion NCS0.692424091156
ens_1d_3AAX-RAY DIFFRACTIONTorsion NCS0.648202716489
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.3-2.340.35241560.28922735X-RAY DIFFRACTION92.49
2.34-2.390.26191530.27292768X-RAY DIFFRACTION92.48
2.39-2.440.26141050.2632786X-RAY DIFFRACTION93.08
2.44-2.50.32291530.26432702X-RAY DIFFRACTION90.67
2.5-2.560.32311240.2522673X-RAY DIFFRACTION88.69
2.56-2.630.31571090.25072747X-RAY DIFFRACTION93.4
2.63-2.710.26631320.24052819X-RAY DIFFRACTION94.19
2.71-2.790.25471630.23062738X-RAY DIFFRACTION92.53
2.8-2.890.26661710.21992730X-RAY DIFFRACTION91.06
2.89-3.010.27491380.22232701X-RAY DIFFRACTION91.03
3.01-3.140.24791460.21412598X-RAY DIFFRACTION87.45
3.15-3.310.25771240.1912778X-RAY DIFFRACTION92.91
3.31-3.510.25141420.18082765X-RAY DIFFRACTION93.44
3.51-3.780.25251330.17772727X-RAY DIFFRACTION92.41
3.78-4.150.2191430.16982615X-RAY DIFFRACTION86.76
4.15-4.740.21831610.14112735X-RAY DIFFRACTION91.84
4.74-5.90.2161330.15322685X-RAY DIFFRACTION90.22
5.9-14.730.17781390.16342677X-RAY DIFFRACTION89.8
Refinement TLS params.

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

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.54206454344-0.793039455334-0.004112851310910.9545266632640.02273911399880.440899619895-0.0461350767921-0.1574908833230.0633070936254-0.005031149633110.01000463302770.015537418045-0.242661806562-0.4065362399150.09318367131860.5172896769850.105415851107-0.02125455432610.641630980720.009215372184490.408445825096-21.420561010873.0526366943-3.4541342795
20.641615963751-0.2270931821270.1156953401121.11389308551-0.1867327269380.5752610682930.0435578548323-0.00174059087558-0.0511011755254-0.05657501422270.01168058627460.09123371779170.131995109927-0.221843029163-0.03463018325580.462122665634-0.0259703968665-0.007420432452870.4692333043620.02338301195320.315906208785-9.1396280590355.9684253985-2.84215400279
31.22755706710.1930671873770.2461311076960.675517324885-0.4011821669080.659953688254-0.200807669346-0.03150533090940.190734739154-0.01783733125910.0593193715073-0.106969985506-0.1241946008320.3211514459510.09878041829640.443366828685-0.0049947601857-0.02342406351960.5740401568860.004180332136850.3592676484288.6601174427867.44656279953.45392057743
41.768282463890.748435444287-0.1557060103492.14671264855-0.05987007090180.8749600420040.123652159252-0.154784995935-0.3777583670020.393065761759-0.312942683846-0.5477765349270.1870143026290.474962500790.1679306667970.4518985963750.005147578668330.01714037099780.6169407575930.103756903650.35598047290513.182971791858.33534088469.73264244534
50.875682607775-0.270778767364-0.4407428839120.195843517480.07895732512920.4379157401380.04145015210450.17964729606-0.25348951805-0.0462731166001-0.1058635554890.0258272354295-0.18229402592-0.1596109612930.03508149939230.47568097486-0.0129700475338-0.02782730652960.605037854867-0.01407073988810.342559186668-16.257278418255.089678202919.338481509
61.316403436780.23807291146-0.3369925152880.8157855304290.6325436884210.708304604405-0.0646125674006-0.0929705409190.2903731580110.246819313539-0.0514737217443-0.28289066486-0.1935795941780.2498502380960.1047607007420.455104458632-0.096934322877-0.01035369673240.420646954054-0.00190458385710.297947508727-29.585886184144.4479388405-19.2400946606
70.9242973961690.893785389999-0.6478418144240.967338958118-0.3194382924722.431538585-0.2279732109740.1719270250770.119862103605-0.1272117637050.28710829801-0.151118613630.0162353886934-0.226513323818-0.03912130318010.492569398138-0.0493462507696-0.008148094677860.49989037050.05402917233220.24438221318-28.472812537939.8331376277-29.484955182
81.343453411240.4222945872860.2367608497591.287911184630.02192934303410.7862199519580.07206553635920.06731055718130.04514269707670.0189091566596-0.078678719870.004756374130180.001153177149420.1655057961790.02236860545490.3106296457120.00468765937764-0.005227117752840.351689348037-0.0116706828280.217945006943-42.55008747626.9236586893-24.3736348744
91.39733524887-0.2290245878970.7859689919021.01116983620.3371163655870.906256912955-0.00540365554934-0.151223206468-0.01039925905570.00390052262829-0.06563913360770.0948693505799-0.331163389434-0.2853532863620.07765183542210.3879514120990.02465190141020.007346646474260.414639350850.01683522156270.254535439199-62.4595976336.3931624703-29.9916595904
100.8955035995680.353210783954-0.2836782451860.594393707848-0.103631145340.8898668688420.125957346427-0.2544287534070.0665406467097-0.00520470732851-0.1080615189280.04716510237480.1336884195430.266286151791-0.03913483561960.4026356728750.00294819678465-0.03198989734580.502482089122-0.03646361671550.263828723552-38.577262851324.1237756178-43.7752890347
111.06024775482-0.5120155342960.03384941838571.06857584071-0.1891918906320.4473521454260.03350321509660.01970521747610.09470855906060.0283458540373-0.06129020324410.0776016214932-0.115277015457-0.1654935655470.03936413201830.3133129593580.00408506840471-0.01312195728630.349697742803-0.004697057004070.201262147119-14.31868687387.917779396750.938665650752
121.083323557980.3245104150050.3774841065030.681838945964-0.3098135359551.7537655379-0.027727541571-0.006213899891580.0187237121614-0.0836825422790.0180602573823-0.0916475419466-0.165399380150.4322441062410.006893188866010.341932308366-0.04520053534990.00973988920130.402166393958-0.006865036042960.1876871250039.434053397241.715909458758.96677787638
130.65959282038-0.531079667373-0.1806063723830.4991994326760.07785816384310.6862716839120.1113095406140.224099825413-0.010317981534-0.110871625796-0.1587412556160.0884057612983-0.279194070141-0.4468639449370.05607299575910.4693121352150.0694088801279-0.02651150193940.672326965694-0.009149460175970.277235845385-16.3889904945-0.094772175143623.911295299
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION

IDRefine TLS-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11chain 'A' and (resid 43 through 133 )AA43 - 1331 - 87
22chain 'A' and (resid 134 through 255 )AA134 - 25588 - 209
33chain 'A' and (resid 256 through 324 )AA256 - 324210 - 278
44chain 'A' and (resid 325 through 356 )AA325 - 356279 - 301
55chain 'A' and (resid 357 through 424 )AA357 - 424302 - 369
66chain 'B' and (resid 43 through 104 )BE43 - 1041 - 62
77chain 'B' and (resid 105 through 132 )BE105 - 13263 - 90
88chain 'B' and (resid 133 through 265 )BE133 - 26591 - 223
99chain 'B' and (resid 266 through 339 )BE266 - 339224 - 297
1010chain 'B' and (resid 340 through 422 )BE340 - 422298 - 376
1111chain 'C' and (resid 43 through 239 )CI43 - 2391 - 197
1212chain 'C' and (resid 240 through 356 )CI240 - 356198 - 308
1313chain 'C' and (resid 357 through 424 )CI357 - 424309 - 376

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