FES
Domain
The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins.
The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes.
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.
Involvement in disease
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). May function as tumor suppressor in melanoma by preventing melanoma cell proliferation; expression is reduced or absent in samples from some melanoma patients (PubMed:28463229). 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:16455651). May promote growth of renal carcinoma cells (PubMed:19082481).
Post-translational modifications
Autophosphorylated on Tyr-713. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.
Tissue Specificity
Widely expressed. Detected in adult colon epithelium (at protein level) (PubMed:16455651, PubMed:19051325). Expressed in melanocytes (at protein level) (PubMed:28463229).
Cellular localization
- Cytoplasm
- Cytosol
- Cytoplasm
- Cytoskeleton
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasmic vesicle
- Golgi apparatus
- Cell junction
- Focal adhesion
- 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.
Alternative names
FPS, FES, Tyrosine-protein kinase Fes/Fps, Feline sarcoma/Fujinami avian sarcoma oncogene homolog, Proto-oncogene c-Fes, Proto-oncogene c-Fps, p93c-fes