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| | <StructureSection load='5kaz' size='340' side='right'caption='[[5kaz]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='5kaz' size='340' side='right'caption='[[5kaz]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kaz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KAZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KAZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kaz]] is a 1 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=5KAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KAZ FirstGlance]. <br> |
| - | </td></tr><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SH2D1B, EAT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <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> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5kaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kaz OCA], [http://pdbe.org/5kaz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kaz RCSB], [http://www.ebi.ac.uk/pdbsum/5kaz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kaz ProSAT]</span></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=5kaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kaz OCA], [https://pdbe.org/5kaz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kaz RCSB], [https://www.ebi.ac.uk/pdbsum/5kaz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kaz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SH21B_HUMAN SH21B_HUMAN]] Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity).[UniProtKB:O35324]<ref>PMID:11689425</ref> <ref>PMID:24687958</ref> <ref>PMID:21219180</ref> | + | [https://www.uniprot.org/uniprot/SH21B_HUMAN SH21B_HUMAN] Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity).[UniProtKB:O35324]<ref>PMID:11689425</ref> <ref>PMID:24687958</ref> <ref>PMID:21219180</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Ewing's Sarcoma transcript-2 (EAT2) also known as SH2D1B is involved in regulation of signalling lymphocytic activation molecule (SLAM) family receptor functions. Cytoplasmic tails of SLAM family receptors contain tyrosine residues which mediate the downstream signal transduction through their phosphorylation. EAT2, composed of a single SH2 domain and a short C-terminal tail, binds to the phosphotyrosine residues and regulates SLAM family receptor signalling. We have determined the crystal structure of the human EAT2 protein in an unliganded form. Compared with the mouse EAT2-peptide complex structure, we observe conformational differences in the loops involved in ligand binding. When compared with SAP, the other single SH2 domain protein in human, EAT2 shows similar binding energies to unphosphorylated ligands. This is inconsistent to the previous data showing low affinity of EAT2 toward unphosphorylated peptides compared to SAP which shows high affinity. Additional factors other than the SH2 domains may contribute to the reported differences.
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| - | | + | |
| - | The X-ray Crystallographic Structure of Human EAT2 (SH2D1B).,Taha M, Nezerwa E, Nam HJ Protein Pept Lett. 2016;23(10):862-866. PMID:27586300<ref>PMID:27586300</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5kaz" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nam, H J]] | + | [[Category: Nam H-J]] |
| - | [[Category: Nezerwa, E]] | + | [[Category: Nezerwa E]] |
| - | [[Category: Taha, M]] | + | [[Category: Taha M]] |
| - | [[Category: Eat2]]
| + | |
| - | [[Category: Sap]]
| + | |
| - | [[Category: Sh2d1b]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Slam]]
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| Structural highlights
Function
SH21B_HUMAN Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity).[UniProtKB:O35324][1] [2] [3]
References
- ↑ Morra M, Lu J, Poy F, Martin M, Sayos J, Calpe S, Gullo C, Howie D, Rietdijk S, Thompson A, Coyle AJ, Denny C, Yaffe MB, Engel P, Eck MJ, Terhorst C. Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells. EMBO J. 2001 Nov 1;20(21):5840-52. PMID:11689425 doi:10.1093/emboj/20.21.5840
- ↑ Perez-Quintero LA, Roncagalli R, Guo H, Latour S, Davidson D, Veillette A. EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase Cgamma, Ca++, and Erk, leading to granule polarization. J Exp Med. 2014 Apr 7;211(4):727-42. doi: 10.1084/jem.20132038. Epub 2014 Mar 31. PMID:24687958 doi:http://dx.doi.org/10.1084/jem.20132038
- ↑ Cannons JL, Tangye SG, Schwartzberg PL. SLAM family receptors and SAP adaptors in immunity. Annu Rev Immunol. 2011;29:665-705. doi: 10.1146/annurev-immunol-030409-101302. PMID:21219180 doi:http://dx.doi.org/10.1146/annurev-immunol-030409-101302
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