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[[Image:2c7m.gif|left|200px]]<br /><applet load="2c7m" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2c7m, resolution 2.40&Aring;" />
'''HUMAN RABEX-5 RESIDUES 1-74 IN COMPLEX WITH UBIQUITIN'''<br />


==Overview==
==Human Rabex-5 residues 1-74 in complex with Ubiquitin==
<StructureSection load='2c7m' size='340' side='right'caption='[[2c7m]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2c7m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] 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=2C7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C7M FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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'>[https://proteopedia.org/fgij/fg.htm?mol=2c7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c7m OCA], [https://pdbe.org/2c7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c7m RCSB], [https://www.ebi.ac.uk/pdbsum/2c7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c7m ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RABX5_HUMAN RABX5_HUMAN] Rab effector protein acting as linker between gamma-adaptin, RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates nucleotide exchange on RAB5A. Can act as a ubiquitin ligase (By similarity).<ref>PMID:9323142</ref> <ref>PMID:11452015</ref> <ref>PMID:15339665</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/c7/2c7m_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=2c7m ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.
The interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling.


==About this Structure==
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.,Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:16499958<ref>PMID:16499958</ref>
2C7M is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C7M OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin., Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR, Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16499958 16499958]
</div>
<div class="pdbe-citations 2c7m" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Rab5 GDP/GTP exchange factor|Rab5 GDP/GTP exchange factor]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Confalioneri, S.]]
[[Category: Confalioneri S]]
[[Category: Fiore, P P.Di.]]
[[Category: Di Fiore PP]]
[[Category: Magri, L.]]
[[Category: Magri L]]
[[Category: Mapelli, M.]]
[[Category: Mapelli M]]
[[Category: Murachelli, A G.]]
[[Category: Murachelli AG]]
[[Category: Musacchio, A.]]
[[Category: Musacchio A]]
[[Category: Penengo, L.]]
[[Category: Penengo L]]
[[Category: Polo, S.]]
[[Category: Polo S]]
[[Category: Schneider, T R.]]
[[Category: Schneider TR]]
[[Category: ZN]]
[[Category: endocytosis]]
[[Category: nuclear protein]]
[[Category: polyprotein]]
[[Category: ubiquitin binding domain]]
[[Category: ubl conjugation]]
 
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