InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FES

Summary

InnateDB Protein

IDBP-380500.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FES

Protein Name

feline sarcoma oncogene

Synonyms

FPS;

Species

Homo sapiens

Ensembl Protein

ENSP00000400868

InnateDB Gene

IDBG-30488 (FES)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:11509660, ECO:0000269PubMed:15302586, ECO:0000269PubMed:15485904, ECO:0000269PubMed:16455651, ECO:0000269PubMed:17595334, ECO:0000269PubMed:18046454, ECO:0000269PubMed:19001085, ECO:0000269PubMed:19051325, ECO:0000269PubMed:20111072, ECO:0000269PubMed:2656706, ECO:0000269PubMed:8955135}.

Subcellular Localization

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.

Disease Associations

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). {ECO:0000269PubMed:16455651, ECO:0000269PubMed:19082481, ECO:0000269PubMed:20111072, ECO:0000269PubMed:21563194, ECO:0000269PubMed:2656706}.

Tissue Specificity

Widely expressed. Detected in adult colon epithelium. {ECO:0000269PubMed:16455651, ECO:0000269PubMed:19051325}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 45 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	45 [view]
Protein-Protein	42 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0034987	immunoglobulin receptor binding
GO:0035091	phosphatidylinositol binding

Biological Process

GO:0006468	protein phosphorylation
GO:0007275	multicellular organismal development
GO:0007411	axon guidance
GO:0008283	cell proliferation
GO:0008360	regulation of cell shape
GO:0010976	positive regulation of neuron projection development
GO:0016192	vesicle-mediated transport
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030155	regulation of cell adhesion
GO:0031116	positive regulation of microtubule polymerization
GO:0042127	regulation of cell proliferation
GO:0043304	regulation of mast cell degranulation
GO:0045595	regulation of cell differentiation
GO:0045639	positive regulation of myeloid cell differentiation
GO:0046777	protein autophosphorylation
GO:0060627	regulation of vesicle-mediated transport
GO:2000145	regulation of cell motility
GO:2000251	positive regulation of actin cytoskeleton reorganization

Cellular Component

GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005925	focal adhesion
GO:0015630	microtubule cytoskeleton
GO:0016020	membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0031234	extrinsic component of cytoplasmic side of plasma membrane
GO:0031410	cytoplasmic vesicle

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001060 FCH domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010989 t-SNARE
IPR011009 Protein kinase-like domain
IPR016250 Tyrosine-protein kinase, Fes/Fps type
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF00611
PF07714

PRINTS

PR00109

PIRSF

PIRSF000632

SMART

SM00055
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References