1wa7: Difference between revisions

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 ==SH3 DOMAIN OF HUMAN LYN TYROSINE KINASE IN COMPLEX WITH A HERPESVIRAL LIGAND==
-<StructureSection load='1wa7' size='340' side='right'caption='[[1wa7]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='1wa7' size='340' side='right'caption='[[1wa7]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1wa7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Herpesvirus_saimiri Herpesvirus saimiri]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WA7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1wa7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saimiriine_gammaherpesvirus_2 Saimiriine gammaherpesvirus 2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WA7 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1w1f|1w1f]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wa7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wa7 OCA], [https://pdbe.org/1wa7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wa7 RCSB], [https://www.ebi.ac.uk/pdbsum/1wa7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wa7 ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/LYN_HUMAN LYN_HUMAN] Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells.<ref>PMID:18056483</ref> <ref>PMID:18235045</ref> <ref>PMID:18577747</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/TIP_SHV2C TIP_SHV2C]] Plays a critical role in virus induced T-cell transformation. Binds to T-cell-specific tyrosine kinase LCK SH2 and SH3 domains, thereby activating its kinase activity. Once phosphorylated by host LCK, forms a complex with at least STAT 1 and 3, resulting on the phosphorylation of STAT3 and presumably STAT1, and their migration into the nucleus to induce transcription of target genes. Stimulates host ILF3/NF-AT-90 activity. Association with host NXF1/TAP transduces the signal up-regulating surface expression of adhesion molecules as well as activating NF-kappa-B activity. Acts synergistically with StpC to stimulate NF-kappa-B activity and interleukin-2 gene expression. Activation of NF-kappa-B protects lymphocytes from apoptosis, thereby facilitating viral induced cell transformation. May cause down-regulation of host LCK and cell apoptosis when stably overexpressed ex vivo. Interaction with WDR48 induce degradation of T-cell receptor in a lysosome-dependent fashion, when both proteins are overexpressed. The biological effect of this interaction remains controversial since no T-cell receptor degradation is observed in infected cells.
+[https://www.uniprot.org/uniprot/LYN_HUMAN LYN_HUMAN] Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'.<ref>PMID:7687428</ref> <ref>PMID:10574931</ref> <ref>PMID:10748115</ref> <ref>PMID:11435302</ref> <ref>PMID:10891478</ref> <ref>PMID:11517336</ref> <ref>PMID:11825908</ref> <ref>PMID:14726379</ref> <ref>PMID:15795233</ref> <ref>PMID:16467205</ref> <ref>PMID:17640867</ref> <ref>PMID:17977829</ref> <ref>PMID:18056483</ref> <ref>PMID:18070987</ref> <ref>PMID:18235045</ref> <ref>PMID:18802065</ref> <ref>PMID:18577747</ref> <ref>PMID:20028775</ref> <ref>PMID:19290919</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 37: @@
 __TOC__
 </StructureSection>
-[[Category: Herpesvirus saimiri]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Transferase]]
+[[Category: Saimiriine gammaherpesvirus 2]]
-[[Category: Bauer, F]]
+[[Category: Bauer F]]
-[[Category: Hoffmann, S]]
+[[Category: Hoffmann S]]
-[[Category: Roesch, P]]
+[[Category: Roesch P]]
-[[Category: Schweimer, K]]
+[[Category: Schweimer K]]
-[[Category: Sticht, H]]
+[[Category: Sticht H]]
-[[Category: Hypothetical protein]]
-[[Category: Ligand]]
-[[Category: Lyn]]
-[[Category: Proto-oncogene]]
-[[Category: Sh3 domain]]
-[[Category: Signal transduction]]
-[[Category: Tip]]
-[[Category: Tyrosine kinase]]