View source for 2uvl


==Human BIR3 domain of Baculoviral Inhibitor of Apoptosis Repeat- Containing 3 (BIRC3)==
<StructureSection load='2uvl' size='340' side='right'caption='[[2uvl]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2uvl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UVL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UVL 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]] 1.91&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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=2uvl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uvl OCA], [https://pdbe.org/2uvl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uvl RCSB], [https://www.ebi.ac.uk/pdbsum/2uvl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uvl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BIRC3_HUMAN BIRC3_HUMAN] Note=A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.
== Function ==
[https://www.uniprot.org/uniprot/BIRC3_HUMAN BIRC3_HUMAN] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8.<ref>PMID:21931591</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/uv/2uvl_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=2uvl ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.

Structures of BIR domains from human NAIP and cIAP2.,Herman MD, Moche M, Flodin S, Welin M, Tresaugues L, Johansson I, Nilsson M, Nordlund P, Nyman T Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Nov 1;65(Pt, 11):1091-6. Epub 2009 Oct 24. PMID:19923725<ref>PMID:19923725</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2uvl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith C]]
[[Category: Berglund H]]
[[Category: Busam R]]
[[Category: Collins R]]
[[Category: Dahlgren LG]]
[[Category: Edwards A]]
[[Category: Flodin S]]
[[Category: Flores A]]
[[Category: Graslund S]]
[[Category: Hallberg BM]]
[[Category: Hammarstrom M]]
[[Category: Holmberg-Schiavone L]]
[[Category: Johansson I]]
[[Category: Karlberg T]]
[[Category: Kotenyova T]]
[[Category: Lehtio L]]
[[Category: Moche M]]
[[Category: Nordlund P]]
[[Category: Nyman T]]
[[Category: Ogg D]]
[[Category: Persson C]]
[[Category: Sagemark J]]
[[Category: Stenmark P]]
[[Category: Sundstrom M]]
[[Category: Thorsell AG]]
[[Category: Upsten M]]
[[Category: Van Den Berg S]]
[[Category: Weigelt J]]