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[[Image:1eh2.gif|left|200px]]<br />
<applet load="1eh2" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1eh2" />
'''STRUCTURE OF THE SECOND EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15, NMR, 20 STRUCTURES'''<br />


==Overview==
==STRUCTURE OF THE SECOND EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15, NMR, 20 STRUCTURES==
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.
<StructureSection load='1eh2' size='340' side='right'caption='[[1eh2]]' scene=''>
== Structural highlights ==
<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='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=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>
== 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.
== 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>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eh/1eh2_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1eh2 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==About this Structure==
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<ref>PMID:9721102</ref>
1EH2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: NPF. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EH2 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9721102 9721102]
</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/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[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: CA]]
[[Category: calcium binding]]
[[Category: ef-hand]]
[[Category: eh domain]]
[[Category: npf binding]]
[[Category: signaling domain]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 15:19:12 2007''
Retrieved from "https://proteopedia.org/1eh2"