3v2x

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<StructureSection load='3v2x' size='340' side='right'caption='[[3v2x]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
<StructureSection load='3v2x' size='340' side='right'caption='[[3v2x]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3v2x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V2X FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3v2x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V2X FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3so8|3so8]], [[3v2o|3v2o]], [[3v31|3v31]]</div></td></tr>
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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]] 1.85&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANKRA, ANKRA2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3v2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v2x OCA], [https://pdbe.org/3v2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v2x RCSB], [https://www.ebi.ac.uk/pdbsum/3v2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v2x ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v2x OCA], [https://pdbe.org/3v2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v2x RCSB], [https://www.ebi.ac.uk/pdbsum/3v2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v2x ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/ANRA2_HUMAN ANRA2_HUMAN]] May facilitate endocytosis by linking megalin to components of the cytoskeleton or endocytic machinery. [[https://www.uniprot.org/uniprot/LRP2_RAT LRP2_RAT]] Acts together with cubilin to mediate HDL endocytosis (By similarity). Receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B.<ref>PMID:7544804</ref>
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[https://www.uniprot.org/uniprot/ANRA2_HUMAN ANRA2_HUMAN] May facilitate endocytosis by linking megalin to components of the cytoskeleton or endocytic machinery.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Ankyrin repeat family A protein 2 (ANKRA2) interacts with the plasma membrane receptor megalin and the class IIa histone deacetylases HDAC4 and HDAC5. We report that the ankyrin repeat domains of ANKRA2 and its close paralog regulatory factor X-associated ankyrin-containing protein (RFXANK) recognize a PxLPxI/L motif found in diverse binding proteins, including HDAC4, HDAC5, HDAC9, megalin, and regulatory factor X, 5 (RFX5). Crystal structures of the ankyrin repeat domain of ANKRA2 in complex with its binding peptides revealed that each of the middle three ankyrin repeats of ANKRA2 recognizes a residue from the PxLPxI/L motif in a tumbler-lock binding mode, with ANKRA2 acting as the lock and the linear binding motif serving as the key. Structural analysis showed that three disease-causing mutations in RFXANK affect residues that are critical for binding to RFX5. These results suggest a fundamental principle of longitudinal recognition of linear sequences by a repeat-type domain. In addition, phosphorylation of serine 350, a residue embedded within the PxLPxI/L motif of HDAC4, impaired the binding of ANKRA2 but generated a high-affinity docking site for 14-3-3 proteins, which may help sequester this HDAC in the cytoplasm. Thus, the binding preference of the PxLPxI/L motif is signal-dependent. Furthermore, proteome-wide screening suggested that a similar phosphorylation-dependent switch may operate in other pathways. Together, our findings uncover a previously uncharacterized sequence- and signal-dependent peptide recognition mode for a repeat-type protein domain.
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Sequence-Specific Recognition of a PxLPxI/L Motif by an Ankyrin Repeat Tumbler Lock.,Xu C, Jin J, Bian C, Lam R, Tian R, Weist R, You L, Nie J, Bochkarev A, Tempel W, Tan CS, Wasney GA, Vedadi M, Gish GD, Arrowsmith CH, Pawson T, Yang XJ, Min J Sci Signal. 2012 May 29;5(226):ra39. PMID:22649097<ref>PMID:22649097</ref>
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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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<div class="pdbe-citations 3v2x" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Arrowsmith, C H]]
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[[Category: Rattus norvegicus]]
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[[Category: Bian, C B]]
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[[Category: Arrowsmith CH]]
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[[Category: Bochkarev, A]]
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[[Category: Bian CB]]
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[[Category: Bountra, C]]
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[[Category: Bochkarev A]]
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[[Category: Edwards, A M]]
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[[Category: Bountra C]]
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[[Category: Kania, J]]
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[[Category: Edwards AM]]
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[[Category: Lam, R]]
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[[Category: Kania J]]
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[[Category: Min, J]]
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[[Category: Lam R]]
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[[Category: Structural genomic]]
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[[Category: Min J]]
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[[Category: Weigelt, J]]
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[[Category: Weigelt J]]
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[[Category: Xu, C]]
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[[Category: Xu C]]
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[[Category: Ank repeat]]
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[[Category: Ankra2]]
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[[Category: Lrp2/megalin]]
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[[Category: Protein binding]]
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[[Category: Sgc]]
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Current revision

Crystal Structure of the Peptide Bound Complex of the Ankyrin Repeat Domains of Human ANKRA2

PDB ID 3v2x

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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