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[[Image:1m27.gif|left|200px]]


{{Structure
==Crystal structure of SAP/FynSH3/SLAM ternary complex==
|PDB= 1m27 |SIZE=350|CAPTION= <scene name='initialview01'>1m27</scene>, resolution 2.5&Aring;
<StructureSection load='1m27' size='340' side='right'caption='[[1m27]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>
<table><tr><td colspan='2'>[[1m27]] is a 3 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=1M27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M27 FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m27 OCA], [https://pdbe.org/1m27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m27 RCSB], [https://www.ebi.ac.uk/pdbsum/1m27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m27 ProSAT]</span></td></tr>
|RELATEDENTRY=[[1d4t|1D4T]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1m27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m27 OCA], [http://www.ebi.ac.uk/pdbsum/1m27 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1m27 RCSB]</span>
== Disease ==
}}
[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>
== Function ==
[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.
== 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/m2/1m27_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=1m27 ConSurf].
<div style="clear:both"></div>


'''Crystal structure of SAP/FynSH3/SLAM ternary complex'''
==See Also==
 
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
 
== References ==
==Overview==
<references/>
SAP (SLAM-associated protein) is a small lymphocyte-specific signalling molecule that is defective or absent in patients with X-linked lymphoproliferative syndrome (XLP). Consistent with its single src homology 2 (SH2) domain architecture and unusually high affinity for SLAM (also called CD150), SAP has been suggested to function by blocking binding of SHP-2 or other SH2-containing signalling proteins to SLAM receptors. Additionally, SAP has recently been shown to be required for recruitment and activation of the Src-family kinase FynT after SLAM ligation. This signalling 'adaptor' function has been difficult to conceptualize, because unlike typical SH2-adaptor proteins, SAP contains only a single SH2 domain and lacks other recognized protein interaction domains or motifs. Here, we show that the SAP SH2 domain binds to the SH3 domain of FynT and directly couples FynT to SLAM. The crystal structure of a ternary SLAM-SAP-Fyn-SH3 complex reveals that SAP binds the FynT SH3 domain through a surface-surface interaction that does not involve canonical SH3 or SH2 binding interactions. The observed mode of binding to the Fyn-SH3 domain is expected to preclude the auto-inhibited conformation of Fyn, thereby promoting activation of the kinase after recruitment. These findings broaden our understanding of the functional repertoire of SH3 and SH2 domains.
__TOC__
 
</StructureSection>
==About this Structure==
1M27 is a [[Protein complex]] structure of sequences 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=1M27 OCA].
 
==Reference==
SAP couples Fyn to SLAM immune receptors., Chan B, Lanyi A, Song HK, Griesbach J, Simarro-Grande M, Poy F, Howie D, Sumegi J, Terhorst C, Eck MJ, Nat Cell Biol. 2003 Feb;5(2):155-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12545174 12545174]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Transferase]]
[[Category: Chan B]]
[[Category: Chan, B.]]
[[Category: Eck MJ]]
[[Category: Eck, M J.]]
[[Category: Griesbach J]]
[[Category: Griesbach, J.]]
[[Category: Poy F]]
[[Category: Poy, F.]]
[[Category: Song HK]]
[[Category: Song, H K.]]
[[Category: Terhorst C]]
[[Category: Terhorst, C.]]
[[Category: sh2-sh3 interaction]]
 
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Retrieved from "https://proteopedia.org/1m27"