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| | <StructureSection load='5jp2' size='340' side='right'caption='[[5jp2]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5jp2' size='340' side='right'caption='[[5jp2]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jp2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JP2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JP2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jp2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JP2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPS15, AF1P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), fcho1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jp2 OCA], [http://pdbe.org/5jp2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jp2 RCSB], [http://www.ebi.ac.uk/pdbsum/5jp2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jp2 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=5jp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jp2 OCA], [https://pdbe.org/5jp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jp2 RCSB], [https://www.ebi.ac.uk/pdbsum/5jp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jp2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN]] Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein. | + | [https://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN] Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN]] Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.<ref>PMID:18362181</ref> <ref>PMID:19458185</ref> <ref>PMID:22648170</ref> <ref>PMID:16903783</ref> | + | [https://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN] Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.<ref>PMID:18362181</ref> <ref>PMID:19458185</ref> <ref>PMID:22648170</ref> <ref>PMID:16903783</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: McCoy, A J]] | + | [[Category: McCoy AJ]] |
| - | [[Category: Owen, D J]] | + | [[Category: Owen DJ]] |
| - | [[Category: Wrobel, A]] | + | [[Category: Wrobel A]] |
| - | [[Category: Fcho eps15 mu homology domain endocytosis]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
EPS15_HUMAN Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein.
Function
EPS15_HUMAN Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.[1] [2] [3] [4]
Publication Abstract from PubMed
Clathrin-coated vesicles form by rapid assembly of discrete coat constituents into a cargo-sorting lattice. How the sequential phases of coat construction are choreographed is unclear, but transient protein-protein interactions mediated by short interaction motifs are pivotal. We show that arrayed Asp-Pro-Phe (DPF) motifs within the early-arriving endocytic pioneers Eps15/R are differentially decoded by other endocytic pioneers Fcho1/2 and AP-2. The structure of an Eps15/RFcho1 mu-homology domain complex reveals a spacing-dependent DPF triad, bound in a mechanistically distinct way from the mode of single DPF binding to AP-2. Using cells lacking FCHO1/2 and with Eps15 sequestered from the plasma membrane, we establish that without these two endocytic pioneers, AP-2 assemblies are fleeting and endocytosis stalls. Thus, distinct DPF-based codes within the unstructured Eps15/R C terminus direct the assembly of temporary Fcho1/2Eps15/RAP-2 ternary complexes to facilitate conformational activation of AP-2 by the Fcho1/2 interdomain linker to promote AP-2 cargo engagement.
Transient Fcho1/2Eps15/RAP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding.,Ma L, Umasankar PK, Wrobel AG, Lymar A, McCoy AJ, Holkar SS, Jha A, Pradhan-Sundd T, Watkins SC, Owen DJ, Traub LM Dev Cell. 2016 Jun 6;37(5):428-43. doi: 10.1016/j.devcel.2016.05.003. Epub 2016, May 26. PMID:27237791[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Roxrud I, Raiborg C, Pedersen NM, Stang E, Stenmark H. An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. J Cell Biol. 2008 Mar 24;180(6):1205-18. doi: 10.1083/jcb.200708115. PMID:18362181 doi:10.1083/jcb.200708115
- ↑ Mettlen M, Stoeber M, Loerke D, Antonescu CN, Danuser G, Schmid SL. Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits. Mol Biol Cell. 2009 Jul;20(14):3251-60. doi: 10.1091/mbc.E09-03-0256. Epub 2009, May 20. PMID:19458185 doi:10.1091/mbc.E09-03-0256
- ↑ Teckchandani A, Mulkearns EE, Randolph TW, Toida N, Cooper JA. The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis. Mol Biol Cell. 2012 Aug;23(15):2905-16. doi: 10.1091/mbc.E11-12-1007. Epub 2012, May 30. PMID:22648170 doi:10.1091/mbc.E11-12-1007
- ↑ Schmid EM, Ford MG, Burtey A, Praefcke GJ, Peak-Chew SY, Mills IG, Benmerah A, McMahon HT. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 2006 Sep;4(9):e262. PMID:16903783 doi:http://dx.doi.org/10.1371/journal.pbio.0040262
- ↑ Ma L, Umasankar PK, Wrobel AG, Lymar A, McCoy AJ, Holkar SS, Jha A, Pradhan-Sundd T, Watkins SC, Owen DJ, Traub LM. Transient Fcho1/2Eps15/RAP-2 Nanoclusters Prime the AP-2 Clathrin Adaptor for Cargo Binding. Dev Cell. 2016 Jun 6;37(5):428-43. doi: 10.1016/j.devcel.2016.05.003. Epub 2016, May 26. PMID:27237791 doi:http://dx.doi.org/10.1016/j.devcel.2016.05.003
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