2dcr: Difference between revisions
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==Fully automated solution structure determination of the Fes SH2 domain== | |||
<StructureSection load='2dcr' size='340' side='right'caption='[[2dcr]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2dcr]] 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=2DCR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DCR 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=2dcr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dcr OCA], [https://pdbe.org/2dcr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dcr RCSB], [https://www.ebi.ac.uk/pdbsum/2dcr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dcr ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481). | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref> <ref>PMID:8955135</ref> <ref>PMID:11509660</ref> <ref>PMID:15302586</ref> <ref>PMID:15485904</ref> <ref>PMID:16455651</ref> <ref>PMID:17595334</ref> <ref>PMID:18046454</ref> <ref>PMID:19051325</ref> <ref>PMID:19082481</ref> <ref>PMID:19001085</ref> <ref>PMID:20111072</ref> <ref>PMID:21563194</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dc/2dcr_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2dcr ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fully automated structure determination of proteins in solution (FLYA) yields, without human intervention, three-dimensional protein structures starting from a set of multidimensional NMR spectra. Integrating existing and new software, automated peak picking over all spectra is followed by peak list filtering, the generation of an ensemble of initial chemical shift assignments, the determination of consensus chemical shift assignments for all (1)H, (13)C, and (15)N nuclei, the assignment of NOESY cross-peaks, the generation of distance restraints, and the calculation of the three-dimensional structure by torsion angle dynamics. The resulting, preliminary structure serves as additional input to the second stage of the procedure, in which a new ensemble of chemical shift assignments and a refined structure are calculated. The three-dimensional structures of three 12-16 kDa proteins computed with the FLYA algorithm coincided closely with the conventionally determined structures. Deviations were below 0.95 A for the backbone atom positions, excluding the flexible chain termini. 96-97% of all backbone and side-chain chemical shifts in the structured regions were assigned to the correct residues. The purely computational FLYA method is suitable for substituting all manual spectra analysis and thus overcomes a main efficiency limitation of the NMR method for protein structure determination. | |||
Automated protein structure determination from NMR spectra.,Lopez-Mendez B, Guntert P J Am Chem Soc. 2006 Oct 11;128(40):13112-22. PMID:17017791<ref>PMID:17017791</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2dcr" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[ | *[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Guntert | [[Category: Guntert P]] | ||
[[Category: Lopez-Mendez | [[Category: Lopez-Mendez B]] | ||