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| | ==Reduced form of ADAP hSH3-N-domain== | | ==Reduced form of ADAP hSH3-N-domain== |
| - | <StructureSection load='2gtj' size='340' side='right'caption='[[2gtj]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2gtj' size='340' side='right'caption='[[2gtj]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2gtj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GTJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2gtj]] 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=2GTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GTJ FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FYB, SLAP130 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=2gtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gtj OCA], [https://pdbe.org/2gtj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gtj RCSB], [https://www.ebi.ac.uk/pdbsum/2gtj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gtj 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=2gtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gtj OCA], [https://pdbe.org/2gtj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gtj RCSB], [https://www.ebi.ac.uk/pdbsum/2gtj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gtj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/FYB1_HUMAN FYB1_HUMAN] Congenital autosomal recessive small-platelet thrombocytopenia. The disease is caused by variants affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FYB_HUMAN FYB_HUMAN]] Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells. Modulates the expression of interleukin-2 (IL-2). Involved in platelet activation. Prevents the degradation of SKAP1 and SKAP2. May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton.<ref>PMID:10747096</ref> <ref>PMID:15849195</ref> <ref>PMID:16980616</ref>
| + | [https://www.uniprot.org/uniprot/FYB1_HUMAN FYB1_HUMAN] Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells (By similarity). May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton (PubMed:10747096, PubMed:16980616). Modulates the expression of IL2 (By similarity). Involved in platelet activation (By similarity). Prevents the degradation of SKAP1 and SKAP2 (PubMed:15849195). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (By similarity).[UniProtKB:D3ZIE4][UniProtKB:O35601]<ref>PMID:10747096</ref> <ref>PMID:15849195</ref> <ref>PMID:16980616</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Freund, C]] | + | [[Category: Freund C]] |
| - | [[Category: Kuehne, R]] | + | [[Category: Kuehne R]] |
| - | [[Category: Zimmermann, J]] | + | [[Category: Zimmermann J]] |
| - | [[Category: Redox]]
| + | |
| - | [[Category: Sh3]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
FYB1_HUMAN Congenital autosomal recessive small-platelet thrombocytopenia. The disease is caused by variants affecting the gene represented in this entry.
Function
FYB1_HUMAN Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells (By similarity). May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton (PubMed:10747096, PubMed:16980616). Modulates the expression of IL2 (By similarity). Involved in platelet activation (By similarity). Prevents the degradation of SKAP1 and SKAP2 (PubMed:15849195). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (By similarity).[UniProtKB:D3ZIE4][UniProtKB:O35601][1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Oxidation-induced conformational changes in proteins provide a powerful mechanism to sense the redox state of a living cell. In contrast to the unspecific and often irreversible oxidation of intracellular proteins during severe oxidative stress, regulatory redox events need to have specific and transient effects on cellular targets. Here we present evidence for the reversible formation of a vicinal disulfide bond in a prototypic protein interaction domain. NMR spectroscopy was used to determine the structure of the N-terminal hSH3 domain (hSH3N) of the immune cell protein ADAP (adhesion and degranulation promoting adapter protein) in the reduced and oxidized states. An eight-membered ring formed upon oxidation of two neighboring cysteines leads to significant changes in the variable arginine-threonine (RT) loop of the hSH3N domain and alters the helix-sheet packing of the domain. The redox potential for this structural transition is -228 mV at pH 7.4. This is compatible with a role of the cysteinylcysteine moiety in redox signaling during T cell activation.
Redox-regulated conformational changes in an SH3 domain.,Zimmermann J, Kuhne R, Sylvester M, Freund C Biochemistry. 2007 Jun 12;46(23):6971-7. Epub 2007 May 19. PMID:17511475[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Krause M, Sechi AS, Konradt M, Monner D, Gertler FB, Wehland J. Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton. J Cell Biol. 2000 Apr 3;149(1):181-94. PMID:10747096
- ↑ Huang Y, Norton DD, Precht P, Martindale JL, Burkhardt JK, Wange RL. Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells. J Biol Chem. 2005 Jun 24;280(25):23576-83. Epub 2005 Apr 22. PMID:15849195 doi:http://dx.doi.org/10.1074/jbc.M413201200
- ↑ Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, Freund C, Kasirer-Friede A, Menasche G, Koretzky GA, Schraven B. The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1. Mol Cell Biol. 2006 Oct;26(19):7130-44. PMID:16980616 doi:http://dx.doi.org/26/19/7130
- ↑ Zimmermann J, Kuhne R, Sylvester M, Freund C. Redox-regulated conformational changes in an SH3 domain. Biochemistry. 2007 Jun 12;46(23):6971-7. Epub 2007 May 19. PMID:17511475 doi:10.1021/bi700437r
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