View source for 4tzi


==Structure of unliganded Lyn SH2 domain==
<StructureSection load='4tzi' size='340' side='right'caption='[[4tzi]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4tzi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TZI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TZI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</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=4tzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tzi OCA], [https://pdbe.org/4tzi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tzi RCSB], [https://www.ebi.ac.uk/pdbsum/4tzi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tzi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LYN_MOUSE LYN_MOUSE] 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. 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:15335855</ref> <ref>PMID:7513017</ref> <ref>PMID:8128248</ref> <ref>PMID:7585947</ref> <ref>PMID:7584145</ref> <ref>PMID:8621063</ref> <ref>PMID:9064343</ref> <ref>PMID:8629002</ref> <ref>PMID:9252121</ref> <ref>PMID:9036984</ref> <ref>PMID:9573010</ref> <ref>PMID:9601638</ref> <ref>PMID:9480991</ref> <ref>PMID:9547345</ref> <ref>PMID:9469421</ref> <ref>PMID:9590210</ref> <ref>PMID:10594694</ref> <ref>PMID:10327049</ref> <ref>PMID:10672044</ref> <ref>PMID:10640270</ref> <ref>PMID:11007759</ref> <ref>PMID:11435302</ref> <ref>PMID:11672542</ref> <ref>PMID:12077122</ref> <ref>PMID:12874221</ref> <ref>PMID:14726379</ref> <ref>PMID:14525964</ref> <ref>PMID:16116174</ref> <ref>PMID:16034130</ref> <ref>PMID:16272347</ref> <ref>PMID:16249387</ref> <ref>PMID:16731527</ref> <ref>PMID:17640867</ref> <ref>PMID:19492092</ref> <ref>PMID:20189992</ref> <ref>PMID:20385881</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y194 impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y194 on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases.

Tyrosine phosphorylation of the Lyn SH2 domain modulates its binding affinity and specificity.,Jin LL, Wybenga-Groot LE, Tong J, Taylor P, Minden MD, Trudel S, McGlade CJ, Moran MF Mol Cell Proteomics. 2015 Jan 13. pii: mcp.M114.044404. PMID:25587033<ref>PMID:25587033</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4tzi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Wybenga-Groot LE]]