FES (FES proto-oncogene, tyrosine kinase)

Gene

• Entrez ID: 2242
• Gene name: FES proto-oncogene, tyrosine kinase
• Gene symbol: FES
• Synonyms: FPS
• Chromosome: 15
• Chromosome location: 15q26.1
• Summary: 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029960	hsa-miR-26b-5p	Microarray	19088304
MIRT734255	hsa-miR-125b-5p	Luciferase reporter assay, Western blot	28389358

Transcription factors

Transcription factor	Regulation	Reference
SP1	Unknown	8657143
SPI1	Unknown	7624145;8657143

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001578	Process	Microtubule bundle formation	IEA
GO:0004713	Function	Protein tyrosine kinase activity	IBA	21873635
GO:0004713	Function	Protein tyrosine kinase activity	IDA	11509660
GO:0004713	Function	Protein tyrosine kinase activity	TAS
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IBA	21873635
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IDA	15485904
GO:0005102	Function	Signaling receptor binding	IBA	21873635
GO:0005515	Function	Protein binding	IPI	18046454, 21044950, 24728074
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IDA	11339827
GO:0005794	Component	Golgi apparatus	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005925	Component	Focal adhesion	IDA	18046454
GO:0006935	Process	Chemotaxis	IBA	21873635
GO:0007098	Process	Centrosome cycle	IEA
GO:0007155	Process	Cell adhesion	IBA	21873635
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0008017	Function	Microtubule binding	IEA
GO:0008360	Process	Regulation of cell shape	IMP	11509660, 18046454
GO:0010976	Process	Positive regulation of neuron projection development	IMP	15302586
GO:0015630	Component	Microtubule cytoskeleton	IDA	15485904
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IDA	11509660, 15485904
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030155	Process	Regulation of cell adhesion	IMP	11509660
GO:0031116	Process	Positive regulation of microtubule polymerization	IMP	15485904
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	IBA	21873635
GO:0031234	Component	Extrinsic component of cytoplasmic side of plasma membrane	IDA	18046454, 19001085
GO:0031410	Component	Cytoplasmic vesicle	IDA	11339827
GO:0034987	Function	Immunoglobulin receptor binding	IDA	19001085
GO:0035091	Function	Phosphatidylinositol binding	IDA	19001085
GO:0042127	Process	Regulation of cell population proliferation	IMP	11509660
GO:0043304	Process	Regulation of mast cell degranulation	IBA	21873635
GO:0043304	Process	Regulation of mast cell degranulation	IMP	19001085
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0045595	Process	Regulation of cell differentiation	IMP	15302586
GO:0045639	Process	Positive regulation of myeloid cell differentiation	IMP	2656706
GO:0045657	Process	Positive regulation of monocyte differentiation	IMP	28389358
GO:0046777	Process	Protein autophosphorylation	IDA	7687763
GO:0060627	Process	Regulation of vesicle-mediated transport	TAS	11339827
GO:0071305	Process	Cellular response to vitamin D	IMP	28389358
GO:2000145	Process	Regulation of cell motility	IMP	18046454
GO:2000251	Process	Positive regulation of actin cytoskeleton reorganization	IMP	15302586

Other IDs

• MIM: 190030
• HGNC: 3657
• e!Ensembl: ENSG00000182511

Protein

• UniProt ID: P07332
• Protein name: Tyrosine-protein kinase Fes/Fps (EC 2.7.10.2) (Feline sarcoma/Fujinami avian sarcoma oncogene homolog) (Proto-oncogene c-Fes) (Proto-oncogene c-Fps) (p93c-fes)
• Protein 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.
• PDB: 1WQU, 2DCR, 3BKB, 3CBL, 3CD3, 4DYL, 4E93, 6JMF
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00611	FCH	12 → 92	Fes/CIP4, and EFC/F-BAR homology domain	Family
  PF00017	SH2	460 → 530	SH2 domain	Domain
  PF07714	PK_Tyr_Ser-Thr	561 → 814	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MGFSSELCSPQGHGVLQQMQEAELRLLEGMRKWMAQRVKSDREYAGLLHHMSLQDSGGQS
  RAISPDSPISQSWAEITSQTEGLSRLLRQHAEDLNSGPLSKLSLLIRERQQLRKTYSEQW
  QQLQQELTKTHSQDIEKLKSQYRALARDSAQAKRKYQEASKDKDRDKAKDKYVRSLWKLF
  AHHNRYVLGVRAAQLHHQHHHQLLLPGLLRSLQDLHEEMACILKEILQEYLEISSLVQDE
  VVAIHREMAAAAARIQPEAEYQGFLRQYGSAPDVPPCVTFDESLLEEGEPLEPGELQLNE
  LTVESVQHTLTSVTDELAVATEMVFRRQEMVTQLQQELRNEEENTHPRERVQLLGKRQVL
  QEALQGLQVALCSQAKLQAQQELLQTKLEHLGPGEPPPVLLLQDDRHSTSSSEQEREGGR
  TPTLEILKSHISGIFRPKFSLPPPLQLIPEVQKPLHEQLWYHGAIPRAEVAELLVHSGDF
  LVRESQGKQEYVLSVLWDGLPRHFIIQSLDNLYRLEGEGFPSIPLLIDHLLSTQQPLTKK
  SGVVLHRAVPKDKWVLNHEDLVLGEQIGRGNFGEVFSGRLRADNTLVAVKSCRETLPPDL
  KAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDFLTFLRTEGARLRVKTL
  LQMVGDAAAGMEYLESKCCIHRDLAARNCLVTEKNVLKISDFGMSREEADGVYAASGGLR
  QVPVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGASPYPNLSNQQTREFVEKGGRLP
  CPELCPDAVFRLMEQCWAYEPGQRPSFSTIYQELQSIRKRHR

• Sequence length: 822

Pathways

KEGG:

Axon guidance

Reactome:

Signaling by SCF-KIT
Sema3A PAK dependent Axon repulsion
CRMPs in Sema3A signaling

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs-1, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	30285260
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	29212778, 28714975, 30104761, 23202125
Myocardial infarction	Myocardial Infarction	rs12316150, rs41303970, rs909253, rs7291467, rs2234693	26343387
Hypertension	Hypertensive disease	rs13306026	21909115

Unknown
Disease name	Disease term	dbSNP ID	References
Cardiovascular diseases	Cardiovascular Diseases		30595370