1blk

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[[Image:1blk.gif|left|200px]]
 
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==NMR ENSEMBLE OF BLK SH2 DOMAIN USING CHEMICAL SHIFT REFINEMENT, 20 STRUCTURES==
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The line below this paragraph, containing "STRUCTURE_1blk", creates the "Structure Box" on the page.
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<StructureSection load='1blk' size='340' side='right'caption='[[1blk]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[1blk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BLK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BLK FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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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=1blk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1blk OCA], [https://pdbe.org/1blk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1blk RCSB], [https://www.ebi.ac.uk/pdbsum/1blk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1blk ProSAT]</span></td></tr>
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{{STRUCTURE_1blk| PDB=1blk | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BLK_MOUSE BLK_MOUSE] Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptor FCGR2. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose.<ref>PMID:2404338</ref> <ref>PMID:7690139</ref> <ref>PMID:7608542</ref> <ref>PMID:7592958</ref> <ref>PMID:7565679</ref> <ref>PMID:9177269</ref> <ref>PMID:9636152</ref> <ref>PMID:14662906</ref> <ref>PMID:12563261</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/1blk_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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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=1blk ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Signal transduction in B cells is mediated, in part, by the interaction of the cytoplasmic components of the antigen receptor complex and various members of the src family tyrosine kinases. Key to this process appears to be the interaction of the tyrosine kinase SH2 domains with the tyrosine-phosphorylated cytoplasmic domain of Ig-alpha, a disulfide-bonded heterodimeric (with Ig-beta or Ig-gamma) transmembrane protein that noncovalently associates with the antigen receptor immunoglobin chains. In addition to binding to the phosphorylated cytoplasmic domains of Ig-alpha and Ig-beta, blk and fyn(T), two members of the src family kinases, have been shown to bind overlapping but distinct sets of phosphoproteins [Malek &amp; Desiderio (1993) J. Biol. Chem. 268. 22557-22565]. A comparison of their three-dimensional structures may elucidate the apparently subtle differences required for phosphoprotein discrimination. To begin characterizing the blk/fyn/phosphosphoprotein interactions, we have determined the three-dimensional solution structure of the SH2 domain of blk kinase by nuclear magnetic resonance (NMR) spectroscopy. 1H, 13C, and 15N resonances of the SH2 domain of blk kinase were assigned by analysis of multidimensional, double- and triple-resonance NMR experiments. Twenty structures of the blk SH2 domain were refined with the program X-PLOR using a total of 2080 experimentally derived conformational restraints. The structures converged to a root-mean-squared (rms) distance deviation of 0.51 and 0.95 A for the backbone atoms and for the non-hydrogen atoms, respectively. The blk SH2 domain adopts the prototypical SH2 fold. Structurally, blk SH2 is most similar to the crystal structure of the v-src SH2 domain [Waksman et al. (1993) Nature 358.646-653] and superimposes on the crystal structure with an rmsd of 1.52 A for the backbone atoms. The largest deviations occur in the four loops interconnecting beta-strands A-E, which are the least well-defined regions in the NMR structure. Exclusion of these loops lowers this rmsd to 0.82 A. The conformation of the BC loop in the blk SH2 domain is similar to the open conformation in the apo lck SH2 domain, suggesting that, like the lck SH2 domain, the blk SH2 domain may have a gated phosphopeptide binding site. Finally, it is proposed that the amino acid substitution of Lys 88 (blk) for Glu [fyn(T)] is important for the observed differences in specificity between blk and fyn(T) SH2 domains.
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'''NMR ENSEMBLE OF BLK SH2 DOMAIN USING CHEMICAL SHIFT REFINEMENT, 20 STRUCTURES'''
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The three-dimensional solution structure of the SH2 domain from p55blk kinase.,Metzler WJ, Leiting B, Pryor K, Mueller L, Farmer BT 2nd Biochemistry. 1996 May 21;35(20):6201-11. PMID:8639560<ref>PMID:8639560</ref>
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==Overview==
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Signal transduction in B cells is mediated, in part, by the interaction of the cytoplasmic components of the antigen receptor complex and various members of the src family tyrosine kinases. Key to this process appears to be the interaction of the tyrosine kinase SH2 domains with the tyrosine-phosphorylated cytoplasmic domain of Ig-alpha, a disulfide-bonded heterodimeric (with Ig-beta or Ig-gamma) transmembrane protein that noncovalently associates with the antigen receptor immunoglobin chains. In addition to binding to the phosphorylated cytoplasmic domains of Ig-alpha and Ig-beta, blk and fyn(T), two members of the src family kinases, have been shown to bind overlapping but distinct sets of phosphoproteins [Malek &amp; Desiderio (1993) J. Biol. Chem. 268. 22557-22565]. A comparison of their three-dimensional structures may elucidate the apparently subtle differences required for phosphoprotein discrimination. To begin characterizing the blk/fyn/phosphosphoprotein interactions, we have determined the three-dimensional solution structure of the SH2 domain of blk kinase by nuclear magnetic resonance (NMR) spectroscopy. 1H, 13C, and 15N resonances of the SH2 domain of blk kinase were assigned by analysis of multidimensional, double- and triple-resonance NMR experiments. Twenty structures of the blk SH2 domain were refined with the program X-PLOR using a total of 2080 experimentally derived conformational restraints. The structures converged to a root-mean-squared (rms) distance deviation of 0.51 and 0.95 A for the backbone atoms and for the non-hydrogen atoms, respectively. The blk SH2 domain adopts the prototypical SH2 fold. Structurally, blk SH2 is most similar to the crystal structure of the v-src SH2 domain [Waksman et al. (1993) Nature 358.646-653] and superimposes on the crystal structure with an rmsd of 1.52 A for the backbone atoms. The largest deviations occur in the four loops interconnecting beta-strands A-E, which are the least well-defined regions in the NMR structure. Exclusion of these loops lowers this rmsd to 0.82 A. The conformation of the BC loop in the blk SH2 domain is similar to the open conformation in the apo lck SH2 domain, suggesting that, like the lck SH2 domain, the blk SH2 domain may have a gated phosphopeptide binding site. Finally, it is proposed that the amino acid substitution of Lys 88 (blk) for Glu [fyn(T)] is important for the observed differences in specificity between blk and fyn(T) SH2 domains.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1BLK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BLK OCA].
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</div>
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<div class="pdbe-citations 1blk" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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The three-dimensional solution structure of the SH2 domain from p55blk kinase., Metzler WJ, Leiting B, Pryor K, Mueller L, Farmer BT 2nd, Biochemistry. 1996 May 21;35(20):6201-11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8639560 8639560]
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*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Single protein]]
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[[Category: Farmer II BT]]
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[[Category: Transferase]]
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[[Category: Leiting B]]
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[[Category: II, B T.Farmer.]]
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[[Category: Metzler WJ]]
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[[Category: Leiting, B.]]
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[[Category: Mueller L]]
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[[Category: Metzler, W J.]]
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[[Category: Pryor K]]
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[[Category: Mueller, L.]]
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[[Category: Pryor, K.]]
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[[Category: Phosphorylation]]
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[[Category: Phosphotransferase]]
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[[Category: Signal transduction]]
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[[Category: Transferase]]
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[[Category: Tyrosine kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:40:17 2008''
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NMR ENSEMBLE OF BLK SH2 DOMAIN USING CHEMICAL SHIFT REFINEMENT, 20 STRUCTURES

PDB ID 1blk

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