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| | ==Structure of the EPS15-EH2 Stonin2 Complex== | | ==Structure of the EPS15-EH2 Stonin2 Complex== |
| - | <StructureSection load='2jxc' size='340' side='right' caption='[[2jxc]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2jxc' size='340' side='right'caption='[[2jxc]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jxc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JXC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jxc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JXC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1eh2|1eh2]], [[1ff1|1ff1]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1eh2|1eh2]], [[1ff1|1ff1]]</div></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]), STON2, STN2, STNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPS15, AF1P ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), STON2, STN2, STNB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2jxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jxc OCA], [http://pdbe.org/2jxc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jxc RCSB], [http://www.ebi.ac.uk/pdbsum/2jxc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jxc 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=2jxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jxc OCA], [https://pdbe.org/2jxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jxc RCSB], [https://www.ebi.ac.uk/pdbsum/2jxc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jxc 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> [[http://www.uniprot.org/uniprot/STON2_HUMAN STON2_HUMAN]] Adapter protein involved in endocytic machinery. May be involved in the vesicle recycling. May facilitate clathrin-coated vesicle uncoating.<ref>PMID:11454741</ref> <ref>PMID:11381094</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> [[https://www.uniprot.org/uniprot/STON2_HUMAN STON2_HUMAN]] Adapter protein involved in endocytic machinery. May be involved in the vesicle recycling. May facilitate clathrin-coated vesicle uncoating.<ref>PMID:11454741</ref> <ref>PMID:11381094</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Groemping, Y]] | | [[Category: Groemping, Y]] |
| | [[Category: Haucke, V]] | | [[Category: Haucke, V]] |
| 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] [STON2_HUMAN] Adapter protein involved in endocytic machinery. May be involved in the vesicle recycling. May facilitate clathrin-coated vesicle uncoating.[5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Eps15 homology (EH) domain-containing proteins play a key regulatory role in intracellular membrane trafficking and cell signalling. EH domains serve as interaction platforms for short peptide motifs comprising the residues NPF within natively unstructured regions of accessory proteins. The EH-NPF interactions described thus far are of very low affinity and specificity. Here, we identify the presynaptic endocytic sorting adaptor stonin2 as a high-affinity ligand for the second EH domain (EH2) of the clathrin accessory protein Eps15. Calorimetric data indicate that both NPF motifs within stonin2 interact with EH2 simultaneously and with sub-micromolar affinity. The solution structure of this complex reveals that the first NPF motif binds to the conserved site on the EH domain, whereas the second motif inserts into a novel hydrophobic pocket. Our data show how combination of two EH-attachment sites provides a means for modulating specificity and allows discrimination from a large pool of potential binding partners containing NPF motifs.
Structure of the Eps15-stonin2 complex provides a molecular explanation for EH-domain ligand specificity.,Rumpf J, Simon B, Jung N, Maritzen T, Haucke V, Sattler M, Groemping Y EMBO J. 2008 Feb 6;27(3):558-69. Epub 2008 Jan 17. PMID:18200045[7]
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
- ↑ Walther K, Krauss M, Diril MK, Lemke S, Ricotta D, Honing S, Kaiser S, Haucke V. Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating. EMBO Rep. 2001 Jul;2(7):634-40. Epub 2001 Jul 3. PMID:11454741 doi:10.1093/embo-reports/kve134
- ↑ Martina JA, Bonangelino CJ, Aguilar RC, Bonifacino JS. Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery. J Cell Biol. 2001 May 28;153(5):1111-20. PMID:11381094
- ↑ Rumpf J, Simon B, Jung N, Maritzen T, Haucke V, Sattler M, Groemping Y. Structure of the Eps15-stonin2 complex provides a molecular explanation for EH-domain ligand specificity. EMBO J. 2008 Feb 6;27(3):558-69. Epub 2008 Jan 17. PMID:18200045 doi:7601980
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