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| | ==STRUCTURE OF THE THIRD EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15== | | ==STRUCTURE OF THE THIRD EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15== |
| - | <StructureSection load='1c07' size='340' side='right'caption='[[1c07]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1c07' size='340' side='right'caption='[[1c07]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1c07]] is a 1 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=1C07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C07 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1c07]] 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=1C07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1C07 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='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'>[https://proteopedia.org/fgij/fg.htm?mol=1c07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c07 OCA], [https://pdbe.org/1c07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c07 RCSB], [https://www.ebi.ac.uk/pdbsum/1c07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c07 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=1c07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c07 OCA], [https://pdbe.org/1c07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1c07 RCSB], [https://www.ebi.ac.uk/pdbsum/1c07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1c07 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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.
| + | [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 == |
| - | [[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/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 1c07" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1c07" 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: De Beer T]] |
| - | [[Category: Enmon, J L]] | + | [[Category: Enmon JL]] |
| - | [[Category: Overduin, M]] | + | [[Category: Overduin M]] |
| - | [[Category: Calcium binding]]
| + | |
| - | [[Category: Ef-hand]]
| + | |
| - | [[Category: Eh domain]]
| + | |
| - | [[Category: Fw binding]]
| + | |
| - | [[Category: Npf binding]]
| + | |
| - | [[Category: Signaling domain]]
| + | |
| - | [[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]
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 interact with proteins involved in endocytosis and signal transduction. EH domains bind to Asn-Pro-Phe (NPF) consensus motifs of target proteins. A few EH domains, such as the third EH domain (EH(3)) of human Eps15, prefer to bind Phe-Trp (FW) sequences. The structure of EH(3) has been solved by nuclear magnetic resonance (NMR) spectroscopy and is the first of an FW- and NPF-binding EH domain. Both FW and NPF sequences bind in the same hydrophobic pocket as shown by heteronuclear chemical shift mapping. EH(3) contains the dual EF-hand fold characteristic of the EH domain family, but it binds calcium with high affinity in the first EF-hand rather than the usual coordination in the second EF-hand. Point mutations were designed based on differences in the EH(3) and the second EH domain (EH(2)) of human Eps15 that alter the affinity of the domains for FW or NPF motif peptides. Peptides that mimic binding sites in the potential EH(3) targets Rab, synaptojanin, and the cation-dependent mannose 6-phosphate receptor were used to explore wild-type and mutant affinities. Characterization of the structure and binding properties of an FW- and NPF-binding EH domain and comparison to an NPF-specific EH domain provide important insights into the mechanisms of EH domain ligand recognition.
Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites.,Enmon JL, de Beer T, Overduin M Biochemistry. 2000 Apr 18;39(15):4309-19. PMID:10757979[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
- ↑ Enmon JL, de Beer T, Overduin M. Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites. Biochemistry. 2000 Apr 18;39(15):4309-19. PMID:10757979
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