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1khx

From Proteopedia

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[[Image:1khx.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of a phosphorylated Smad2==
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|PDB= 1khx |SIZE=350|CAPTION= <scene name='initialview01'>1khx</scene>, resolution 1.8&Aring;
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<StructureSection load='1khx' size='340' side='right'caption='[[1khx]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1khx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KHX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KHX FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1khx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1khx OCA], [https://pdbe.org/1khx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1khx RCSB], [https://www.ebi.ac.uk/pdbsum/1khx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1khx ProSAT]</span></td></tr>
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</table>
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'''Crystal structure of a phosphorylated Smad2'''
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== Function ==
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[https://www.uniprot.org/uniprot/SMAD2_HUMAN SMAD2_HUMAN] Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.<ref>PMID:9892009</ref> <ref>PMID:16751101</ref> <ref>PMID:17327236</ref> <ref>PMID:16862174</ref> <ref>PMID:19289081</ref>
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== Evolutionary Conservation ==
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==Overview==
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[[Image:Consurf_key_small.gif|200px|right]]
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Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine-phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways.
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Check<jmol>
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<jmolCheckbox>
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==About this Structure==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kh/1khx_consurf.spt"</scriptWhenChecked>
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1KHX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KHX OCA].
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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==Reference==
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</jmolCheckbox>
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Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling., Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, Rigotti DJ, Kyin S, Muir TW, Fairman R, Massague J, Shi Y, Mol Cell. 2001 Dec;8(6):1277-89. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11779503 11779503]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1khx ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Chai, J.]]
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[[Category: Chai J]]
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[[Category: Fairman, R.]]
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[[Category: Fairman R]]
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[[Category: Hu, M.]]
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[[Category: Hu M]]
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[[Category: Huse, M.]]
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[[Category: Huse M]]
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[[Category: Kyin, S.]]
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[[Category: Kyin S]]
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[[Category: Massague, J.]]
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[[Category: Massague J]]
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[[Category: Muir, T W.]]
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[[Category: Muir TW]]
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[[Category: Seoane, J.]]
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[[Category: Seoane J]]
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[[Category: Shi, Y.]]
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[[Category: Shi Y]]
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[[Category: Wu, J W.]]
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[[Category: Wu J-W]]
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[[Category: cancer]]
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[[Category: phosphorylation]]
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[[Category: receptor kinase signaling]]
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[[Category: smad2]]
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[[Category: tgf-beta signaling]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:17:42 2008''
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Current revision

Crystal structure of a phosphorylated Smad2

PDB ID 1khx

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