Solution structure of sh2 domain of proto-oncogene tyrosine-protein kinase fer from homo sapiens, northeast structural genomics consortium (nesg) target hr3461dSolution structure of sh2 domain of proto-oncogene tyrosine-protein kinase fer from homo sapiens, northeast structural genomics consortium (nesg) target hr3461d
Structural highlights
2kk6 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
FER_HUMAN Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus.[1][2][3][4][5][6][7][8][9][10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
↑Makovski A, Yaffe E, Shpungin S, Nir U. Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells. J Biol Chem. 2012 Feb 24;287(9):6100-12. doi: 10.1074/jbc.M111.327106. Epub 2012 , Jan 5. PMID:22223638 doi:http://dx.doi.org/10.1074/jbc.M111.327106
↑Kim L, Wong TW. The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors. Mol Cell Biol. 1995 Aug;15(8):4553-61. PMID:7623846
↑Kim L, Wong TW. Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the cytoplasmic tyrosine kinase FER. J Biol Chem. 1998 Sep 4;273(36):23542-8. PMID:9722593
↑Kogata N, Masuda M, Kamioka Y, Yamagishi A, Endo A, Okada M, Mochizuki N. Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells. Mol Biol Cell. 2003 Sep;14(9):3553-64. Epub 2003 Jun 13. PMID:12972546 doi:http://dx.doi.org/10.1091/mbc.E03-02-0080
↑Miravet S, Piedra J, Castano J, Raurell I, Franci C, Dunach M, Garcia de Herreros A. Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription. Mol Cell Biol. 2003 Oct;23(20):7391-402. PMID:14517306
↑Oh MA, Choi S, Lee MJ, Choi MC, Lee SA, Ko W, Cance WG, Oh ES, Buday L, Kim SH, Lee JW. Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes. Biochim Biophys Acta. 2009 May;1793(5):781-91. doi: 10.1016/j.bbamcr.2009.01.015., Epub 2009 Feb 5. PMID:19339212 doi:http://dx.doi.org/10.1016/j.bbamcr.2009.01.015
↑Zoubeidi A, Rocha J, Zouanat FZ, Hamel L, Scarlata E, Aprikian AG, Chevalier S. The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth. Mol Cancer Res. 2009 Jan;7(1):142-55. doi: 10.1158/1541-7786.MCR-08-0117. PMID:19147545 doi:http://dx.doi.org/10.1158/1541-7786.MCR-08-0117
↑Itoh T, Hasegawa J, Tsujita K, Kanaho Y, Takenawa T. The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration. Sci Signal. 2009 Sep 8;2(87):ra52. doi: 10.1126/scisignal.2000393. PMID:19738202 doi:http://dx.doi.org/10.1126/scisignal.2000393
↑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
↑Guo C, Stark GR. FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-kappaB. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7968-73. doi:, 10.1073/pnas.1105369108. Epub 2011 Apr 25. PMID:21518868 doi:http://dx.doi.org/10.1073/pnas.1105369108
