View source for 2mrj


==Structure of Fyn protein SH2 bound==
<StructureSection load='2mrj' size='340' side='right'caption='[[2mrj]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2mrj]] 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=2MRJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MRJ FirstGlance]. <br>
</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=2mrj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mrj OCA], [https://pdbe.org/2mrj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mrj RCSB], [https://www.ebi.ac.uk/pdbsum/2mrj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mrj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FYN_HUMAN FYN_HUMAN] Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1.<ref>PMID:7822789</ref> <ref>PMID:7568038</ref> <ref>PMID:11005864</ref> <ref>PMID:11162638</ref> <ref>PMID:11536198</ref> <ref>PMID:12788081</ref> <ref>PMID:12640114</ref> <ref>PMID:14761972</ref> <ref>PMID:15557120</ref> <ref>PMID:14707117</ref> <ref>PMID:15536091</ref> <ref>PMID:16387660</ref> <ref>PMID:16841086</ref> <ref>PMID:17194753</ref> <ref>PMID:18056706</ref> <ref>PMID:18258597</ref> <ref>PMID:19179337</ref> <ref>PMID:19652227</ref> <ref>PMID:20100835</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Src kinase activity is controlled by various mechanisms involving a coordinated movement of kinase and regulatory domains. Notwithstanding the extensive knowledge related to the backbone dynamics, little is known about the more subtle side-chain dynamics within the regulatory domains and their role in the activation process. Here, we show through experimental methyl dynamic results and predicted changes in side-chain conformational couplings that the SH2 structure of Fyn contains a dynamic network capable of propagating binding information. We reveal that binding the phosphorylated tail of Fyn perturbs a residue cluster near the linker connecting the SH2 and SH3 domains of Fyn, which is known to be relevant in the regulation of the activity of Fyn. Biochemical perturbation experiments validate that those residues are essential for inhibition of Fyn, leading to a gain of function upon mutation. These findings reveal how side-chain dynamics may facilitate the allosteric regulation of the different members of the Src kinase family.

Dynamically Coupled Residues within the SH2 Domain of FYN Are Key to Unlocking Its Activity.,Huculeci R, Cilia E, Lyczek A, Buts L, Houben K, Seeliger MA, van Nuland N, Lenaerts T Structure. 2016 Sep 28. pii: S0969-2126(16)30266-0. doi:, 10.1016/j.str.2016.08.016. PMID:27692963<ref>PMID:27692963</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2mrj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Buts L]]
[[Category: Huculeci R]]
[[Category: Lenaerts T]]
[[Category: Van Nuland N]]