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| | ==F-BAR domain of human FES tyrosine kinase== | | ==F-BAR domain of human FES tyrosine kinase== |
| - | <StructureSection load='4dyl' size='340' side='right' caption='[[4dyl]], [[Resolution|resolution]] 2.18Å' scene=''> | + | <StructureSection load='4dyl' size='340' side='right'caption='[[4dyl]], [[Resolution|resolution]] 2.18Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dyl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DYL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DYL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dyl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DYL FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FES, FPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.18Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 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=4dyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dyl OCA], [https://pdbe.org/4dyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dyl RCSB], [https://www.ebi.ac.uk/pdbsum/4dyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dyl ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4dyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dyl OCA], [http://pdbe.org/4dyl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dyl RCSB], [http://www.ebi.ac.uk/pdbsum/4dyl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dyl ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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). | + | [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 == | | == Function == |
| - | [[http://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> | + | [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> |
| | + | |
| | + | ==See Also== |
| | + | *[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific protein-tyrosine kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Barr, A]] | + | [[Category: Barr A]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bountra C]] |
| - | [[Category: Delft, F von]]
| + | [[Category: Edwards A]] |
| - | [[Category: Edwards, A]] | + | [[Category: Elkins J]] |
| - | [[Category: Elkins, J]] | + | [[Category: Filippakopoulos P]] |
| - | [[Category: Filippakopoulos, P]] | + | [[Category: Knapp S]] |
| - | [[Category: Knapp, S]] | + | [[Category: Krojer T]] |
| - | [[Category: Krojer, T]] | + | [[Category: Salah E]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Ugochukwu E]] |
| - | [[Category: Salah, E]] | + | [[Category: Weigelt J]] |
| - | [[Category: Ugochukwu, E]] | + | [[Category: Von Delft F]] |
| - | [[Category: Weigelt, J]] | + | |
| - | [[Category: Bcr]] | + | |
| - | [[Category: Crk-associated substrate]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
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
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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]
See Also
References
- ↑ Yu G, Smithgall TE, Glazer RI. K562 leukemia cells transfected with the human c-fes gene acquire the ability to undergo myeloid differentiation. J Biol Chem. 1989 Jun 15;264(17):10276-81. PMID:2656706
- ↑ Li J, Smithgall TE. Co-expression with BCR induces activation of the FES tyrosine kinase and phosphorylation of specific N-terminal BCR tyrosine residues. J Biol Chem. 1996 Dec 20;271(51):32930-6. PMID:8955135
- ↑ Cheng HY, Schiavone AP, Smithgall TE. A point mutation in the N-terminal coiled-coil domain releases c-Fes tyrosine kinase activity and survival signaling in myeloid leukemia cells. Mol Cell Biol. 2001 Sep;21(18):6170-80. PMID:11509660
- ↑ Laurent CE, Smithgall TE. The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner. Exp Cell Res. 2004 Sep 10;299(1):188-98. PMID:15302586 doi:10.1016/j.yexcr.2004.05.010
- ↑ Laurent CE, Delfino FJ, Cheng HY, Smithgall TE. The human c-Fes tyrosine kinase binds tubulin and microtubules through separate domains and promotes microtubule assembly. Mol Cell Biol. 2004 Nov;24(21):9351-8. PMID:15485904 doi:10.1128/MCB.24.21.9351-9358.2004
- ↑ Delfino FJ, Stevenson H, Smithgall TE. A growth-suppressive function for the c-fes protein-tyrosine kinase in colorectal cancer. J Biol Chem. 2006 Mar 31;281(13):8829-35. Epub 2006 Feb 2. PMID:16455651 doi:10.1074/jbc.M507331200
- ↑ Voisset E, Lopez S, Dubreuil P, De Sepulveda P. The tyrosine kinase FES is an essential effector of KITD816V proliferation signal. Blood. 2007 Oct 1;110(7):2593-9. Epub 2007 Jun 26. PMID:17595334 doi:10.1182/blood-2007-02-076471
- ↑ Naba A, Reverdy C, Louvard D, Arpin M. Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering. EMBO J. 2008 Jan 9;27(1):38-50. Epub 2007 Nov 29. PMID:18046454 doi:10.1038/sj.emboj.7601943
- ↑ Shaffer JM, Smithgall TE. Promoter methylation blocks FES protein-tyrosine kinase gene expression in colorectal cancer. Genes Chromosomes Cancer. 2009 Mar;48(3):272-84. doi: 10.1002/gcc.20638. PMID:19051325 doi:10.1002/gcc.20638
- ↑ Kanda S, Miyata Y, Kanetake H, Smithgall TE. Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells. Int J Oncol. 2009 Jan;34(1):89-96. PMID:19082481
- ↑ McPherson VA, Everingham S, Karisch R, Smith JA, Udell CM, Zheng J, Jia Z, Craig AW. Contributions of F-BAR and SH2 domains of Fes protein tyrosine kinase for coupling to the FcepsilonRI pathway in mast cells. Mol Cell Biol. 2009 Jan;29(2):389-401. doi: 10.1128/MCB.00904-08. Epub 2008 Nov, 10. PMID:19001085 doi:10.1128/MCB.00904-08
- ↑ Voisset E, Lopez S, Chaix A, Georges C, Hanssens K, Prebet T, Dubreuil P, De Sepulveda P. FES kinases are required for oncogenic FLT3 signaling. Leukemia. 2010 Apr;24(4):721-8. doi: 10.1038/leu.2009.301. Epub 2010 Jan 28. PMID:20111072 doi:10.1038/leu.2009.301
- ↑ Miyata Y, Watanabe S, Matsuo T, Hayashi T, Sakai H, Xuan JW, Greer PA, Kanda S. Pathological significance and predictive value for biochemical recurrence of c-Fes expression in prostate cancer. Prostate. 2012 Feb 1;72(2):201-8. doi: 10.1002/pros.21422. Epub 2011 May 11. PMID:21563194 doi:10.1002/pros.21422
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