1d1z

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[[Image:1d1z.gif|left|200px]]
 
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==CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP==
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The line below this paragraph, containing "STRUCTURE_1d1z", creates the "Structure Box" on the page.
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<StructureSection load='1d1z' size='340' side='right'caption='[[1d1z]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1d1z]] is a 4 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=1D1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D1Z FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_1d1z| PDB=1d1z | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1d1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d1z OCA], [https://pdbe.org/1d1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d1z RCSB], [https://www.ebi.ac.uk/pdbsum/1d1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d1z ProSAT]</span></td></tr>
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</table>
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'''CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP'''
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== Disease ==
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[https://www.uniprot.org/uniprot/SH21A_HUMAN SH21A_HUMAN] Defects in SH2D1A are a cause of lymphoproliferative syndrome X-linked type 1 (XLP1) [MIM:[https://omim.org/entry/308240 308240]; also known as X-linked lymphoproliferative disease (XLPD) or Duncan disease. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:11477068</ref> <ref>PMID:9771704</ref> <ref>PMID:11823424</ref> <ref>PMID:10598819</ref> <ref>PMID:11049992</ref> <ref>PMID:11034354</ref> <ref>PMID:11493483</ref> <ref>PMID:14674764</ref> <ref>PMID:15841490</ref> <ref>PMID:16720617</ref>
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== Function ==
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==Overview==
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[https://www.uniprot.org/uniprot/SH21A_HUMAN SH21A_HUMAN] Inhibitor of the SLAM self-association. Acts by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. Mediates interaction between FYN and SLAMF1. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.
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SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==About this Structure==
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Check<jmol>
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1D1Z is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D1Z OCA].
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d1/1d1z_consurf.spt"</scriptWhenChecked>
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==Reference==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition., Poy F, Yaffe MB, Sayos J, Saxena K, Morra M, Sumegi J, Cantley LC, Terhorst C, Eck MJ, Mol Cell. 1999 Oct;4(4):555-61. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10549287 10549287]
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1d1z ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Eck, M J.]]
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[[Category: Eck MJ]]
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[[Category: Poy, F.]]
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[[Category: Poy F]]
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[[Category: Saxena, K.]]
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[[Category: Saxena K]]
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[[Category: Sayos, J.]]
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[[Category: Sayos J]]
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[[Category: Yaffe, M B.]]
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[[Category: Yaffe MB]]
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[[Category: Sh2 domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:21:37 2008''
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Current revision

CRYSTAL STRUCTURE OF THE XLP PROTEIN SAP

PDB ID 1d1z

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