View source for 5mk0


==Crystal structure of the His Domain Protein Tyrosine Phosphatase (HD-PTP/PTPN23) Bro1 domain (Endofin peptide complex)==
<StructureSection load='5mk0' size='340' side='right' caption='[[5mk0]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mk0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MK0 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN23, KIAA1471 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>
<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=5mk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mk0 OCA], [http://pdbe.org/5mk0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mk0 RCSB], [http://www.ebi.ac.uk/pdbsum/5mk0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mk0 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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>  [[http://www.uniprot.org/uniprot/ZFY16_HUMAN ZFY16_HUMAN]] May be involved in regulating membrane trafficking in the endosomal pathway. Overexpression induces endosome aggregation. Required to target TOM1 to endosomes.<ref>PMID:11546807</ref> <ref>PMID:14613930</ref>  
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== 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>
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<div class="pdbe-citations 5mk0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Gahloth, D]]
[[Category: Levy, C]]
[[Category: Escrt-iii endofin]]
[[Category: Hydrolase]]