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| | ==STRUCTURE OF THE SECOND EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15, NMR, 20 STRUCTURES== | | ==STRUCTURE OF THE SECOND EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15, NMR, 20 STRUCTURES== |
| - | <StructureSection load='1eh2' size='340' side='right'caption='[[1eh2]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1eh2' size='340' side='right'caption='[[1eh2]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1eh2]] is a 1 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=1EH2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1EH2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1eh2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EH2 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPS15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1eh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eh2 OCA], [http://pdbe.org/1eh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1eh2 RCSB], [http://www.ebi.ac.uk/pdbsum/1eh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1eh2 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=1eh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eh2 OCA], [https://pdbe.org/1eh2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1eh2 RCSB], [https://www.ebi.ac.uk/pdbsum/1eh2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1eh2 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1eh2" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1eh2" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Epidermal growth factor receptor substrate 3D structures|Epidermal growth factor receptor substrate 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Beer, T De]] | + | [[Category: Carter RE]] |
| - | [[Category: Carter, R E]] | + | [[Category: De Beer T]] |
| - | [[Category: Lobel-Rice, K E]] | + | [[Category: Lobel-Rice KE]] |
| - | [[Category: Overduin, M]] | + | [[Category: Overduin M]] |
| - | [[Category: Sorkin, A]] | + | [[Category: Sorkin A]] |
| - | [[Category: Calcium binding]]
| + | |
| - | [[Category: Ef-hand]]
| + | |
| - | [[Category: Eh domain]]
| + | |
| - | [[Category: Npf binding]]
| + | |
| - | [[Category: Signaling domain]]
| + | |
| 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]
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) domains are eukaryotic signaling modules that recognize proteins containing Asn-Pro-Phe (NPF) sequences. The structure of the central EH domain of Eps15 has been solved by heteronuclear magnetic resonance spectroscopy. The fold consists of a pair of EF hand motifs, the second of which binds tightly to calcium. The NPF peptide is bound in a hydrophobic pocket between two alpha helices, and binding is mediated by a critical aromatic interaction as revealed by structure-based mutagenesis. The fold is predicted to be highly conserved among 30 identified EH domains and provides a structural basis for defining EH-mediated events in protein trafficking and growth factor signaling.
Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain.,de Beer T, Carter RE, Lobel-Rice KE, Sorkin A, Overduin M Science. 1998 Aug 28;281(5381):1357-60. PMID:9721102[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ de Beer T, Carter RE, Lobel-Rice KE, Sorkin A, Overduin M. Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain. Science. 1998 Aug 28;281(5381):1357-60. PMID:9721102
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