Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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DAVID Functional Annotation Table
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FYN proto-oncogene, Src family tyrosine kinase(FYN) FYN proto-oncogene, Src family tyrosine kinase(FYN) Related Genes Homo sapiens
CHROMOSOME 6,
CYTOBAND 6q21,
ENSEMBL_GENE_ID ENSG00000010810,
GENERIF_SUMMARY Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling, Src-kinase p59(fyn) play a role in anergy induction in CD8+ T cells., the distinct potential of Fyn and Lck to phosphorylate Sam68 is likely controlled by the interaction of the kinase SH3 domain with the linker and Sam68, possibly on a competitive binding basis., identification of novel isoform fynDelta7, in which exon 7 is absent, The Fyn but not the Lck tyrosine kinase SH3 domain competes with CD2BP2 GYF-domain binding to the same CD2 proline-rich sequence in vitro. CD2BP2 is replaced by Fyn SH3 after CD2 is translocated into lipid rafts upon CD2 ectodomain clustering., High expression of FYN is restricted to low-stage tumors and predicts long-term survival. In culture, expression of active Fyn kinase induces differentiation and growth arrest of neuroblastoma cells., Data show that the SLAM-associated protein (SAP) SH2 domain binds to the SH3 domain of FynT and directly couples FynT to SLAM., There was an increase in both total area Fyn mRNA signal (17.7%, P<0.05) and cellular mRNA content (15.7%, P<0.05) in schizophrenic brains relative to controls., p250GAP is phosphorylated by Fyn in oligodendrocytes., upon ligation of integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it, activating a pathway leading to activation of the matrix metalloproteinase-3 gene, and promoting oral SCC cell proliferation and experimental metastasis in vivo, tr-kit promotes the formation of a multimolecular complex composed of Fyn, PLCgamma1 and Sam68, which allows phosphorylation of PLCgamma1 by Fyn, and may modulate RNA metabolism., Two Src kinases are selectively activated by TPO signaling in primary megakaryocytes, Fyn and Lyn, but only Fyn expression is significantly upregulated during MK differentiation, suggesting variable gene regulation., Our results indicate a possible association of alcohol dependence with a genotype of the SNP T137346C of the PTK fyn, with C being the risk allele., Tyrosine phosphorylated tau is distributed in Alzheimer disease brain differently from other phosphorylated tau. Evidence of differentially phosphorylated tau within degenerating neurons was found supporting a role for fyn in neurodegeneration, LYN and FYN are downregulated by CBL in osteoblast differentiation induced by constitutive FGFR2 activation, activation of Fyn is inhibited by NSAIDs and constitutively active Fyn reverses the NSAID-dependent stress kinase inhibition, determined that Fyn phosphorylated MAP-2c on tyrosine 67, Fyn kinase plays a key role in the UVB-induced phosphorylation of histone H3 at serine 10, Alterations in Fyn localization might be associated with neurofibrillary pathology and synapse loss in Alzheimer's disease., PEDF downregulates Fyn through Fes, resulting in inhibition of FGF-2-induced capillary morphogenesis of endothelial cells, calcium activates PLC-gamma1 via increased PIP3 formation mediated by c-src- and fyn-activated PI3K, the Fyn-tau interaction has a role in neurodegeneration, independent of one another Fyn and MAP-2c are able to induce process outgrowth and in concert can initiate and enhance process outgrowth in an additive manner., Increased Fyn expression is sufficient to trigger prominent neuronal deficits in FYN/human amyloid precursor protein transgenic mice in the context of even relatively moderate Abeta levels., Cells with single Src family kinase knockdown show that Src, Fyn and Yes kinases are all required for vascular endothelial growth factor (VEGF) mitogenic signaling in retinal microvascular endothelial cells., Fibronectin rigidity response involves force-dependent Fyn phosphorylation of p130Cas with rigidity-dependent displacement., Fyn suppresses the GTPase-activating protein (GAP) activity of wild-type brain-enriched Rho GTPase-activating protein TCGAP but not the Y406F mutant of TCGAP in a phosphorylation-dependent manner., Staurosporine binds to the ATP-binding site of Fyn in a similar manner as in the Lck- and Csk-complexes, These results indicate that Fyn is activated by G-protein-coupled receptor stimulation and is responsible for transactivation of TrkA receptors on intracellular membranes., extracellular matrix fragments produced by apoptotic EC initiate a state of resistance to apoptosis in fibroblasts via an alpha2beta1 integrin/SFK (Src and Fyn)/phosphatidylinositol 3-kinase (PI3K)-dependent pathway, Glucocorticoids causes dissociation of T-cell receptor associated protein complex containing LCK and FYN., TNF-alpha regulates the pulmonary vascular endothelial paracellular pathway, in part, through fyn activation., The extra-domain B binding D3 protein opens new biomedical opportunities for the in vivo imaging of solid tumorsand for the delivery of toxic agents to the tumoral vasculature., Polymorphisms of the Fyn gene is related to the function of glutamatergic system, and a performance on neuropsychological test of prefrontal cortex activity in schizophrenic patients., the mechanism of signal transduction by CD244 is to regulate FYN kinase recruitment and/or activity and the outcome of CD48/CD244 interactions is determined by which other receptors are engaged., Fyn is weakly phosphorylated in normal B cells, but strongly phosphorylated in myeloma B cells., The results of this study may suggest a relationship between the FYN gene polymorphisms and allergic asthma, Chromosomal deletion, promoter hypermethylation and downregulation of FYN is associated with prostate cancer, engagement of the SH2 domain on PAG renders FynT insensitive to Csk negative regulation, Fyn, due in part to its effects on Dab1, regulates the phosphorylation, trafficking, and processing of APP and apoEr2., Up-regulation, in contrast to activation, of the ubiquitously expressed Src kinase, Fyn, by BCR-ABL1, is described., NS5A binds to the Fyn SH3 domain with what can be considered a high affinity SH3 domain-ligand interaction (629 nM), and this binding did not require the presence of domain I of NS5A (amino acid residues 32-250)., DNMTs activity may have an indirect influence on the expression of Fyn without altering the methylation level of its promoter in Hut-78 T-lymphoma cells., H2O2 significantly inhibited Cl(-)/OH(-) exchange activity in Caco-2 cells. H(2)O(2)-mediated inhibition of Cl(-)/OH(-) exchange activity involved the Src kinase Fyn and PI3K (phosphoinositide 3-kinase)-dependent pathways., PECAM-1 and Fyn are essential components of a PECAM-1-based mechanosensory complex in endothelial cells, Analysis reveals that the Fyn SH2 domain forms a noisy communication channel that couples residues located in the phosphopeptide and specificity binding sites and a number of residues at the other side of the domain., tyrosine phosphorylation of Neph1 mediated by Fyn results in significantly increased Neph1 and ZO-1 binding, suggesting a critical role for Neph1 tyrosine phosphorylation in reorganizing the Neph1-ZO-1 complex., Mutation of Sp1 and Egr1 binding sites within the essential region diminished Fyn promoter activity and identified Egr1 as conferring redox sensitivity., Endocytosis of flotillins is regulated by the Src family kinase Fyn., These results suggest that SFK trafficking is specified by the palmitoylation state in the SH4 domain., The results of the study demonstrated only marginal association between FYN polymorphisms and prophylactic lithium response in bipolar, The results suggest that the glutamatergic FYN gene may be associated with bipolar disorder, particularly with type I illness and early age of onset., These results suggest novel deficits in Fyn function, manifested as the downregulation of Fyn protein or the altered transcription of the fyn gene, in patients with schizophrenia., Mounting evidence summarized in this review suggests that tyrosine kinase Fyn and c-Abl are critical in the neurodegenerative process which occurs in tauopathies., Increased expression of Fyn is associated with resistance to BCR-ABL inhibitors in chronic myelogenous leukemia., a mechanism linking EGFR signaling with Fyn and Src activation to promote glioblastoma progression and invasion in vivo, Fyn is suggested to play an essential role in signaling events that implicate spindle assembly checkpoint pathway and hence in regulating the exit from metaphase in oocytes and zygote., Results describe on a molecular level how Fyn kinase uses alternative splicing to adapt to different cellular environments., brain-specific PTPRT regulates synapse formation through interaction with cell adhesion molecules, and this function and the phosphatase activity are attenuated through tyrosine phosphorylation by the synaptic tyrosine kinase Fyn., Gbeta1-mediated Fyn activation integrates FAK with AJ, preventing persistent endothelial barrier leakiness., Data confirm previous observations of higher expression of CD70 in CD4+ T cells from patients with SLE, and suggest that increased Fyn protein content in CD4+ T cells can be associated with high SLE disease activity., Suggest a possible mechanism by which Fyn activity regulates cell proliferation and apoptosis that exerts an effect on pancreatic cancer metastasis., Data demonstrate that CRMP1 tyrosine 504 is a primary target of the Src family of tyrosine kinases (SFKs), specifically Fyn., These findings indicate that phosphorylation of S21 within the pPKA recognition site (RxxS motif) of Fyn regulates its tyrosine kinase activity and controls focal adhesion targeting., Activation of Fyn promoted SCC cell migration and its suppression thwarted SCC migration toward FN. These results indicate that the activation of Fyn kinase as well as local growth factor concentration modulate EMT in oral SCC., Data describe how alpha6beta4 integrin selectively activates Fyn in response to receptor engagement, and show that both catalytic and noncatalytic functions of SHP2 are required for Fyn activation by alpha6beta4., Results highlight an important role for the Fyn/ERK signaling pathway in imatinib-resistant cells that is driven by accumulation of intracellular SPARC., Here we report the (1)H, (15)N and (13)C backbone and side-chain chemical shift assignments of the SH2 domain of the human protein tyrosine kinase Fyn., Fyn plays an important role in prostate cancer biology by facilitating cellular growth and by regulating directed chemotaxis-a key component of metastasis., Fyn, a member of Src family tyrosine kinases, plays a critical role in mediating TGF-beta1-induced down-regulation of E-cadherin in human A549 lung cancer cells., Data show that the Ras/PI3K/Akt pathway can account for Fyn over-expression in cancers., Fyn phosphorylates Tim-1 and binds Tim-1 in the absence of tyrosine 299 in 293T cells. Fyn is required for phosphorylation of Tim-1 in B cells., Negative regulation of Gq-mediated pathways in platelets by G(12/13) pathways through Fyn kinase, High Fyn expression is associated with pancreatic cancer progression., Pro216 in tau PXXP motif plays role in interaction of tau with Fyn-SH3; phosphorylation of tau at Tyr18 is important for mediating Fyn-SH2-tau interactions; tyrosine phosphorylation influences tau localization in cortical neurons which is Fyn-dependent, Data show that a higher percentage of classical Hodgkin lymphoma cases expressing Lyn, Fyn and Syk compared with previous reports., CD5 glycoprotein-mediated T cell inhibition dependent on inhibitory phosphorylation of Fyn kinase, [review] Recent evidence cited in this review suggests that alterations in Fyn, a Src family kinase, might contribute to Alzheimer's disease pathogenesis., TM4SF10, possibly through ADAP, may regulate Fyn activity, characterized the folding kinetics of a Fyn SH3 domain variant containing 5 amino acid substitutions that was computationally designed to optimize surface charge-charge interactions; results show that optimized Fyn SH3 domain is stabilized through an 8-fold acceleration in the folding rate., Fyn is not required for the pathogenesis of Bcr-Abl-mediated leukemias., Double RNA interference knockdown of Fyn and Lyn induced apoptosis accompanied by caspase-8 activation in NCI-H2052 and ACC-MESO-4 cells., The protein phosphatase PP2A/Balpha binds to the microtubule-associated proteins Tau and MAP2 at a motif also recognized by the kinase Fyn., X-ray data were collected to a resolution of 2.00 A for the unbound form and 1.40 A for the Fyn in complex with the phosphotyrosine peptide, Oxidative injury caused by arachidonic acid and iron enhanced Fyn phosphorylation at a tyrosine residue., c-Src but not Fyn promotes proper spindle orientation in early prometaphase, Fyn mediates postsynaptic density protein- 95Y523 phosphorylation, which may be responsible for the excitotoxic signal cascades and neuronal apoptosis in brain ischemia and amyloid-beta peptide neurotoxicity., these results demonstrate a Fyn kinase-dependent mechanism through which IFNgamma regulates E-cadherin stability and suggest a novel mechanism of disruption of epithelial cell contact, which could contribute to perturbed epithelial barrier function., tau interacts in a phosphorylation-dependent manner with the PSD95-Fyn-NMDA receptor complex at the postsynaptic site, The results presented from this in silico study will open up new prospect for genetic analysis of FYN gene and their correlation with clinical data will be very useful in understanding the genetics of Alzheimer's disease., analysis of binding of the Fyn SH3 domain to a peptide from the NS5A protein, Highlighted is recent evidence that FYN kinase mediates signal transduction downstream of the PrP(C)-ABETA oligomer complex in Alzheimer disease. [review], results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner, we showed that gene dosage of Prnp regulates amyloid beta-induced Fyn/tau alterations, Nck may facilitate dynamic signaling events at the slit diaphragm by promoting Fyn-dependent phosphorylation of nephrin., no association between FYN polymorphisms and schizophrenia risk or age at schizophrenia onset, was found., the non-catalytic functions of the kinases Fyn and Pyk2 were required for late stage human T cell adhesion., positively regulates IFN-lambda1 genes during viral infection, Fyn regulates the activity of the adipogenic transcription factor signal transducer and activator of transcription 5a (STAT5a) through enhancing its interaction with the GTPase phosphoinositide 3-kinase enhancer A (PIKE-A)., Expression of HPV type 16 E7 resulted in increase in Src and Yes proteins level, but did not alter the level of Fyn., MicroRNA-125a-3p reduces cell proliferation and migration by targeting Fyn., PrP(C) down-regulated tau via the Fyn pathway and the effect can be regulated by Abeta oligomers., Fyn expression in mdMSCs contributes to basal cytoskeletal architecture and, when associated with FAs, functions as a proximal mechanical effector for environmental signals that influence MSC lineage allocation., These results provided suggestive evidence that the FYN gene contributes toward the variance in human coping styles., monomeric IgE, in the absence of antigen, induces VEGF production in MC and in vivo contributes to melanoma tumor growth through a Fyn kinase-dependent mechanism., These data demonstrate a mechanism whereby Fyn and Lyn, redundantly mediate anticryptococcal killing by inducing the polarization of perforin-containing granules to the NK cell-cryptococcal synapse., Mutations in FYN implicate SRC signaling, impaired DNA damage response, and escape from immune surveillance mechanisms in the pathogenesis of peripheral T cell lymphomas., The SNPs in the selected regions of the Fyn gene are unlikely to confer the susceptibility of sAD in the Chinese Han population, Results indicate that FYN has an important role in tamoxifen resistance, and its subcellular localization in breast tumor cells may be an important novel biomarker of response to endocrine therapy in breast cancer., Fyn inhibition may be an effective therapeutic approach in treating cSCC., the main finding is that FYN polymorphisms were respon- sible for the variance in intermediate defense style(undoing)and mature defensestyle(suppression)., it is not just inactivation of Fyn that promotes multicellular spheroid formation but this must be coupled with the full length beta6 integrin., Fyn, but not Lyn, was required for complete Pyk2 phosphorylation by thrombin., Mutation of Fyn phosphorylation sites on PIKE-A, depletion of Fyn, or pharmacological inhibition of Fyn blunts the association between PIKE-A and AMPK, resulting in loss of its inhibitory effect on AMPK., Our results establish that Fyn can arrest SW-induced apoptosis via the activity of Akt and its effective phosphorylation in 293T cells., Results show that Fyn differentially modulates Nav1.5 channel splice variants. It phosphorylates Nav1.5 variants Q-del and Q-pre resulting in there hyperpolarizing and depolarizing shift. Fyn's activity is abolished in the presence of both variants., our results provide no evidence that the Fyn -93A>G SNP contributes to the susceptibility to acute liver transplant rejection in a Caucasian population., In this study, it is shown that the alternatively spliced FynT isoform is specifically up-regulated in the AD neocortex, with no change in FynB isoform., Data suggest both KLF5 (Kruppel like factor 5) and FYN are important in regulation of migration in bladder cancer cells; KLF5 up-regulates cell migration, lamellipodia formation, FYN expression, and phosphorylation of FAK (focal adhesion kinase).,
OFFICIAL_GENE_SYMBOL FYN,
SP_COMMENT catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate., cofactor:Manganese., enzyme regulation:Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site., function:Implicated in the control of cell growth. Plays a role in the regulation of intracellular calcium levels, with isoform 2 showing the greater ability to mobilize cytoplasmic calcium in comparison to isoform 1. Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension. Blocks axon outgrowth and attraction induced by NTN1 by phosphorylating its receptor DDC., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily., similarity:Contains 1 protein kinase domain., similarity:Contains 1 SH2 domain., similarity:Contains 1 SH3 domain., subcellular location:Present and active in lipid rafts. Present in cell body and along the process of mature and developing oligodendroyctes., subunit:Associates through its SH3 domain, to the p85 subunit of phosphatidylinositol 3-kinase. Interacts with the FYN-binding protein (FYB). Interacts with phosphorylated TOM1L1. Interacts with CD79A upon activation of the B-cell antigen receptor which increases FYN activity (By similarity). Interacts with PAG1. Interacts (via SH3 domain) with PRMT8. Interacts with SH2D1A and SLAMF1. Interacts (via SH3 domain) with HEV ORF3 protein., tissue specificity:Isoform 1 is highly expressed in the brain, isoform 2 is expressed in cells of hemopoietic lineages, especially T lymphocytes.,