Description: Homo sapiens feline sarcoma oncogene (FES), transcript variant 1, mRNA. RefSeq Summary (NM_002005): This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]. Transcript (Including UTRs) Position: hg19 chr15:91,427,665-91,439,006 Size: 11,342 Total Exon Count: 19 Strand: + Coding Region Position: hg19 chr15:91,428,276-91,438,788 Size: 10,513 Coding Exon Count: 18
ID:FES_HUMAN DESCRIPTION: RecName: Full=Tyrosine-protein kinase Fes/Fps; EC=2.7.10.2; AltName: Full=Feline sarcoma/Fujinami avian sarcoma oncogene homolog; AltName: Full=Proto-oncogene c-Fes; AltName: Full=Proto-oncogene c-Fps; AltName: Full=p93c-fes; FUNCTION: 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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Kinase activity is tightly regulated. Activated in response to signaling from a cell surface receptor. Activation probably requires binding of a substrate via the SH2 domain, plus autophosphorylation at Tyr-713. Present in an inactive form in the absence of activating stimuli. SUBUNIT: Homooligomer. Interacts with BCR. Interacts (when activated, via coiled coil domain) with TRIM28. Interacts (via SH2 domain) with phosphorylated EZR, MS4A2/FCER1B and HCLS1/HS1. Interacts with phosphorylated KIT. Interacts with FLT3. Interacts (via FCH domain) with soluble tubulin. Interacts (via SH2 domain) with microtubules. SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesicle. Golgi apparatus. Cell junction, focal adhesion. Note=Distributed throughout the cytosol when the kinase is not activated. Association with microtubules requires activation of the kinase activity. Shuttles between focal adhesions and cell-cell contacts in epithelial cells. Recruited to the lateral cell membrane in polarized epithelial cells by interaction with phosphorylated EZR. Detected at tubular membrane structures in the cytoplasm and at the cell periphery. TISSUE SPECIFICITY: Widely expressed. Detected in adult colon epithelium. DOMAIN: The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins. DOMAIN: The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes. PTM: Autophosphorylated on Tyr-713. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK. DISEASE: 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). MISCELLANEOUS: Cellular homolog of retroviral oncogenes. In constrast to the viral oncoproteins, the kinase activity of cellular FSP/FES is tightly regulated, and the kinase is inactive in normal cells in the absence of activating stimuli (PubMed:15485904). SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily. SIMILARITY: Contains 1 FCH domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain.
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): FES CDC HuGE Published Literature: FES Positive Disease Associations: Blood Pressure
, Hypertension Related Studies:
Blood Pressure Louise V Wain et al. Nature genetics 2011, Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure., Nature genetics.
[PubMed 21909110]
Blood Pressure Georg B Ehret et al. Nature 2011, Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk., Nature.
[PubMed 21909115]
Hypertension Georg B Ehret et al. Nature 2011, Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk., Nature.
[PubMed 21909115]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P07332
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
