View source for 5mk2


==Crystal structure of the His Domain Protein Tyrosine Phosphatase (HD-PTP/PTPN23) Bro1 domain (CHMP4B peptide complex structure)==
<StructureSection load='5mk2' size='340' side='right'caption='[[5mk2]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mk2]] 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=5MK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MK2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</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=5mk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mk2 OCA], [https://pdbe.org/5mk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mk2 RCSB], [https://www.ebi.ac.uk/pdbsum/5mk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mk2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PTN23_HUMAN PTN23_HUMAN] Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis.<ref>PMID:18434552</ref> <ref>PMID:20393563</ref> <ref>PMID:21757351</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SARA and endofin are endosomal adaptor proteins that drive Smad phosphorylation by ligand-activated transforming growth factor beta/bone morphogenetic protein (TGFbeta/BMP) receptors. We show in this study that SARA and endofin also recruit the tumor supressor HD-PTP, a master regulator of endosomal sorting and ESCRT-dependent receptor downregulation. High-affinity interactions occur between the SARA/endofin N termini, and the conserved hydrophobic region in the HD-PTP Bro1 domain that binds CHMP4/ESCRT-III. CHMP4 engagement is a universal feature of Bro1 proteins, but SARA/endofin binding is specific to HD-PTP. Crystallographic structures of HD-PTPBro1 in complex with SARA, endofin, and three CHMP4 isoforms revealed that all ligands bind similarly to the conserved site but, critically, only SARA/endofin interact at a neighboring pocket unique to HD-PTP. The structures, together with mutagenesis and binding analysis, explain the high affinity and specific binding of SARA/endofin, and why they compete so effectively with CHMP4. Our data invoke models for how endocytic regulation of TGFbeta/BMP signaling is controlled.

Structural Basis for Specific Interaction of TGFbeta Signaling Regulators SARA/Endofin with HD-PTP.,Gahloth D, Levy C, Walker L, Wunderley L, Mould AP, Taylor S, Woodman P, Tabernero L Structure. 2017 Jul 5;25(7):1011-1024.e4. doi: 10.1016/j.str.2017.05.005. Epub, 2017 Jun 8. PMID:28602823<ref>PMID:28602823</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mk2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Charged multivesicular body protein 3D structures|Charged multivesicular body protein 3D structures]]
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gahloth D]]
[[Category: Levy C]]