View source for 2ysf


==Solution structure of the fourth WW domain from the human E3 ubiquitin-protein ligase Itchy homolog, ITCH==
<StructureSection load='2ysf' size='340' side='right'caption='[[2ysf]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ysf]] 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=2YSF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YSF 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ysf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ysf OCA], [https://pdbe.org/2ysf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ysf RCSB], [https://www.ebi.ac.uk/pdbsum/2ysf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ysf ProSAT], [https://www.topsan.org/Proteins/RSGI/2ysf TOPSAN]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ITCH_HUMAN ITCH_HUMAN] Defects in ITCH are the cause of syndromic multisystem autoimmune disease (SMAD) [MIM:[https://omim.org/entry/613385 613385]. SMAD is characterized by organomegaly, failure to thrive, developmental delay, dysmorphic features and autoimmune inflammatory cell infiltration of the lungs, liver and gut.<ref>PMID:20170897</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ITCH_HUMAN ITCH_HUMAN] Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. It catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation. It is involved in the control of inflammatory signaling pathways. Is an essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of the complex after TNF stimulation. Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1. Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways. Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response. Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages. Critical regulator of T-helper (TH2) cytokine development through its ability to induce JUNB ubiquitination and degradation (By similarity). Ubiquitinates SNX9. Ubiquitinates CXCR4 and HGS/HRS and regulates sorting of CXCR4 to the degradative pathway. It is involved in the negative regulation of MAVS-dependent cellular antiviral responses. Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation. Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP. Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID. Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination.<ref>PMID:14602072</ref> <ref>PMID:17028573</ref> <ref>PMID:16387660</ref> <ref>PMID:18718448</ref> <ref>PMID:18718449</ref> <ref>PMID:18628966</ref> <ref>PMID:19592251</ref> <ref>PMID:19131965</ref> <ref>PMID:19881509</ref> <ref>PMID:20392206</ref> <ref>PMID:20068034</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/ys/2ysf_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=2ysf ConSurf].
<div style="clear:both"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Harada T]]
[[Category: Kigawa T]]
[[Category: Koshiba S]]
[[Category: Li H]]
[[Category: Ohnishi S]]
[[Category: Watanabe S]]
[[Category: Yokoyama S]]