5hky

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'''Unreleased structure'''
 
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The entry 5hky is ON HOLD until Paper Publication
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==Crystal structure of c-Cbl TKBD domain in complex with SPRY2 peptide (36-60, pY55) Refined to 1.8A Resolution (P6 form)==
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<StructureSection load='5hky' size='340' side='right' caption='[[5hky]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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Authors: Lovell, S., Battaile, K.P., Mehzabeen, N., Zhang, N., Cooper, A., Gao, P., Perez, R.P.
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5hky]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HKY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HKY FirstGlance]. <br>
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Description: Crystal structure of c-Cbl TKBD domain in complex with SPRY2 peptide (36-60, pY55) Refined to 1.8A Resolution (P6 form)
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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[[Category: Unreleased Structures]]
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hl0|5hl0]], [[5hkw|5hkw]], [[5hkx|5hkx]], [[5hkz|5hkz]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hky OCA], [http://pdbe.org/5hky PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hky RCSB], [http://www.ebi.ac.uk/pdbsum/5hky PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hky ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Defects in CBL are the cause of Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:[http://omim.org/entry/613563 613563]]. A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects.<ref>PMID:20619386</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function.<ref>PMID:10514377</ref> <ref>PMID:11896602</ref> <ref>PMID:14739300</ref> <ref>PMID:15190072</ref> <ref>PMID:17509076</ref> <ref>PMID:18374639</ref> <ref>PMID:19689429</ref> <ref>PMID:21596750</ref> [[http://www.uniprot.org/uniprot/SPY2_HUMAN SPY2_HUMAN]] May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.<ref>PMID:10887178</ref>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Battaile, K P]]
[[Category: Cooper, A]]
[[Category: Cooper, A]]
[[Category: Gao, P]]
[[Category: Gao, P]]
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[[Category: Battaile, K.P]]
 
[[Category: Lovell, S]]
[[Category: Lovell, S]]
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[[Category: Mehzabeen, N]]
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[[Category: Perez, R P]]
[[Category: Zhang, N]]
[[Category: Zhang, N]]
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[[Category: Mehzabeen, N]]
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[[Category: Anticancer target]]
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[[Category: Perez, R.P]]
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[[Category: Cbl]]
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[[Category: Ligase]]
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[[Category: Protein-protein interaction]]
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[[Category: Spry2]]

Revision as of 00:42, 19 January 2017

Crystal structure of c-Cbl TKBD domain in complex with SPRY2 peptide (36-60, pY55) Refined to 1.8A Resolution (P6 form)

5hky, resolution 1.80Å

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