2izv

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[[Image:2izv.png|left|200px]]
 
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{{STRUCTURE_2izv| PDB=2izv | SCENE= }}
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==CRYSTAL STRUCTURE OF SOCS-4 IN COMPLEX WITH ELONGIN-B AND ELONGIN-C AT 2.55A RESOLUTION==
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<StructureSection load='2izv' size='340' side='right'caption='[[2izv]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2izv]] is a 3 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=2IZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IZV FirstGlance]. <br>
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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]] 2.55&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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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=2izv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2izv OCA], [https://pdbe.org/2izv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2izv RCSB], [https://www.ebi.ac.uk/pdbsum/2izv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2izv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ELOC_HUMAN ELOC_HUMAN] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:15590694</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iz/2izv_consurf.spt"</scriptWhenChecked>
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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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</jmolCheckbox>
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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=2izv ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Tyrosine kinase signaling is tightly controlled by negative feedback inhibitors including suppressors of cytokine signaling (SOCS). SOCS assemble as SH2 domain substrate recognition modules in ElonginB/C-cullin ubiquitin ligases. In accordance, SOCS4 reduces STAT3 signaling from EGFR through increased receptor degradation. Variable C-termini in SOCS4-SOCS7 exclude these family members from a SOCS2-type domain arrangement in which a strictly conserved C terminus determines domain packing. The structure of the SOCS4-ElonginC-ElonginB complex reveals a distinct SOCS structural class. The N-terminal ESS helix functionally replaces the CIS/SOCS1-SOCS3 family C terminus in a distinct SH2-SOCS box interface that facilitates further interdomain packing between the extended N- and C-terminal regions characteristic for this subfamily. Using peptide arrays and calorimetry the STAT3 site in EGFR (pY(1092)) was identified as a high affinity SOCS4 substrate (K(D) = 0.5 microM) revealing a mechanism for EGFR degradation. SOCS4 also bound JAK2 and KIT with low micromolar affinity, whereas SOCS2 was specific for GH-receptor.
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===CRYSTAL STRUCTURE OF SOCS-4 IN COMPLEX WITH ELONGIN-B AND ELONGIN-C AT 2.55A RESOLUTION===
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Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation.,Bullock AN, Rodriguez MC, Debreczeni JE, Songyang Z, Knapp S Structure. 2007 Nov;15(11):1493-504. PMID:17997974<ref>PMID:17997974</ref>
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{{ABSTRACT_PUBMED_17997974}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2izv" style="background-color:#fffaf0;"></div>
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[[2izv]] is a 3 chain structure with 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=2IZV OCA].
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==See Also==
==See Also==
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*[[Elongation factor|Elongation factor]]
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*[[Elongation factor 3D structures|Elongation factor 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017997974</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arrowsmith, C.]]
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[[Category: Large Structures]]
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[[Category: Bullock, A.]]
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[[Category: Arrowsmith C]]
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[[Category: Debreczeni, J E.]]
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[[Category: Bullock A]]
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[[Category: Delft, F Von.]]
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[[Category: Debreczeni JE]]
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[[Category: Edwards, A.]]
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[[Category: Edwards A]]
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[[Category: Gorrec, F.]]
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[[Category: Gorrec F]]
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[[Category: Knapp, S.]]
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[[Category: Knapp S]]
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[[Category: Papagrigoriou, E.]]
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[[Category: Papagrigoriou E]]
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[[Category: Pike, A C.W.]]
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[[Category: Pike ACW]]
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[[Category: Sundstrom, M.]]
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[[Category: Sundstrom M]]
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[[Category: Turnbull, A.]]
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[[Category: Turnbull A]]
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[[Category: Weigelt, J.]]
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[[Category: Weigelt J]]
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[[Category: Growth regulation]]
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[[Category: Von Delft F]]
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[[Category: Nuclear protein]]
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[[Category: Sh2 domain]]
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[[Category: Signal transduction]]
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[[Category: Signal transduction inhibitor]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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[[Category: Ubl conjugation pathway]]
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Current revision

CRYSTAL STRUCTURE OF SOCS-4 IN COMPLEX WITH ELONGIN-B AND ELONGIN-C AT 2.55A RESOLUTION

PDB ID 2izv

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