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P07332 (FES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 165. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase Fes/Fps

EC=2.7.10.2
Alternative name(s):
Feline sarcoma/Fujinami avian sarcoma oncogene homolog
Proto-oncogene c-Fes
Proto-oncogene c-Fps
p93c-fes
Gene names
Name:FES
Synonyms:FPS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length822 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.8 Ref.10 Ref.12 Ref.14 Ref.15 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.27 Ref.29

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.8 Ref.9 Ref.12 Ref.15 Ref.16 Ref.31

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. Ref.10 Ref.31

Subunit structure

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. Ref.12 Ref.14 Ref.15 Ref.18 Ref.21 Ref.22 Ref.25 Ref.27

Subcellular location

Cytoplasmcytosol. Cytoplasmcytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesicle. Golgi apparatus. Cell junctionfocal 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. Ref.11 Ref.15 Ref.19 Ref.21 Ref.22 Ref.25

Tissue specificity

Widely expressed. Detected in adult colon epithelium. Ref.19 Ref.23

Domain

The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins. Ref.12 Ref.22

The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes. Ref.12 Ref.22

Post-translational modification

Autophosphorylated on Tyr-713. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK. Ref.9 Ref.10 Ref.12 Ref.15 Ref.16 Ref.21 Ref.22 Ref.25 Ref.27 Ref.31

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 (Ref.27). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (Ref.8). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (Ref.19). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (Ref.19). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (Ref.29). May promote growth of renal carcinoma cells (Ref.24).

Miscellaneous

Cellular homolog of retroviral oncogenes. In contrast 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 (Ref.15).

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.

Contains 1 FCH domain.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoplasmic vesicle
Cytoskeleton
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseProto-oncogene
Tumor suppressor
   DomainCoiled coil
SH2 domain
   LigandATP-binding
Lipid-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Traceable author statement. Source: Reactome

cell proliferation

Traceable author statement PubMed 6264598. Source: ProtInc

multicellular organismal development

Traceable author statement PubMed 6264598. Source: ProtInc

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.12Ref.15. Source: UniProtKB

positive regulation of actin cytoskeleton reorganization

Inferred from mutant phenotype Ref.14. Source: UniProtKB

positive regulation of microtubule polymerization

Inferred from mutant phenotype Ref.15. Source: UniProtKB

positive regulation of myeloid cell differentiation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of neuron projection development

Inferred from mutant phenotype Ref.14. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.9. Source: UniProtKB

protein phosphorylation

Traceable author statement PubMed 6183005. Source: ProtInc

regulation of cell adhesion

Inferred from mutant phenotype Ref.12. Source: UniProtKB

regulation of cell differentiation

Inferred from mutant phenotype Ref.14. Source: UniProtKB

regulation of cell motility

Inferred from mutant phenotype Ref.21. Source: UniProtKB

regulation of cell proliferation

Inferred from mutant phenotype Ref.12. Source: UniProtKB

regulation of cell shape

Inferred from mutant phenotype Ref.12Ref.21. Source: UniProtKB

regulation of mast cell degranulation

Inferred from mutant phenotype Ref.25. Source: UniProtKB

regulation of vesicle-mediated transport

Traceable author statement Ref.11. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay Ref.11. Source: UniProtKB

cytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

extrinsic component of cytoplasmic side of plasma membrane

Inferred from direct assay Ref.21Ref.25. Source: UniProtKB

focal adhesion

Inferred from direct assay Ref.21. Source: UniProtKB

microtubule cytoskeleton

Inferred from direct assay Ref.15. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

immunoglobulin receptor binding

Inferred from direct assay Ref.25. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.15. Source: UniProtKB

phosphatidylinositol binding

Inferred from direct assay Ref.25. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.21PubMed 24728074. Source: IntAct

protein tyrosine kinase activity

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P07332-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P07332-2)

Also known as: Variant 1;

The sequence of this isoform differs from the canonical sequence as follows:
     72-129: Missing.
     441-510: Missing.
Isoform 3 (identifier: P07332-3)

Also known as: Variant 3;

The sequence of this isoform differs from the canonical sequence as follows:
     72-129: Missing.
Isoform 4 (identifier: P07332-4)

Also known as: Variant 4;

The sequence of this isoform differs from the canonical sequence as follows:
     441-510: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 822822Tyrosine-protein kinase Fes/Fps
PRO_0000088088

Regions

Domain1 – 6969FCH
Domain460 – 54990SH2
Domain561 – 822262Protein kinase
Nucleotide binding567 – 5759ATP By similarity
Region1 – 300300Important for interaction with membranes containing phosphoinositides
Coiled coil125 – 16945 Potential
Coiled coil324 – 36845 Potential

Sites

Active site6831Proton acceptor By similarity
Binding site5901ATP By similarity

Amino acid modifications

Modified residue641Phosphoserine Ref.26
Modified residue671Phosphoserine Ref.26
Modified residue2611Phosphotyrosine Ref.26
Modified residue4211Phosphothreonine Ref.27
Modified residue7131Phosphotyrosine; by autocatalysis Ref.9 Ref.15 Ref.21 Ref.22 Ref.26 Ref.31
Modified residue7161Phosphoserine Ref.26

Natural variations

Alternative sequence72 – 12958Missing in isoform 2 and isoform 3.
VSP_041748
Alternative sequence441 – 51070Missing in isoform 2 and isoform 4.
VSP_041749
Natural variant851R → C. Ref.32
Corresponds to variant rs56041861 [ dbSNP | Ensembl ].
VAR_041697
Natural variant2461R → Q. Ref.32
Corresponds to variant rs34573430 [ dbSNP | Ensembl ].
VAR_041698
Natural variant3231M → V. Ref.32
Corresponds to variant rs56296062 [ dbSNP | Ensembl ].
VAR_041699

Experimental info

Mutagenesis113 – 1142RK → EE: Reduced binding to membranes containing phosphoinositides. Ref.25
Mutagenesis113 – 1142RK → QQ: Reduced binding to membranes containing phosphoinositides. Ref.25
Mutagenesis1451L → P: Constitutively activated kinase that can act as oncogene. Promotes myeloid cell survival and proliferation. Ref.12 Ref.15 Ref.25
Mutagenesis3341L → P: Abolishes autophosphorylation. Ref.12 Ref.25
Mutagenesis4631G → V: Abolishes kinase activity. Ref.25 Ref.31
Mutagenesis4831R → M: Abolishes pTyr binding. Abolishes association with microtubules. Abolishes autophosphorylation. Reduced kinase activity. Ref.15 Ref.25 Ref.31
Mutagenesis5901K → E: Abolishes kinase activity. Ref.15 Ref.25
Mutagenesis7041M → V: Reduced autophosphorylation and strongly reduced kinase activity. Ref.16 Ref.19 Ref.25
Mutagenesis7061R → Q: Negligible effect on autophosphorylation and kinase activity. Ref.16 Ref.19 Ref.25
Mutagenesis7131Y → F: Reduces kinase activity by over 90%. Ref.9 Ref.25
Mutagenesis7431V → M: Strongly reduced autophosphorylation and kinase activity. Ref.16 Ref.19 Ref.25
Mutagenesis7591S → F: Reduced autophosphorylation and strongly reduced kinase activity. Ref.16 Ref.19 Ref.25
Sequence conflict7191L → S in CAA36438. Ref.1
Sequence conflict7191L → S in AAS82866. Ref.3
Sequence conflict7191L → S in AAS82869. Ref.3
Sequence conflict7191L → S in AAS82868. Ref.3

Secondary structure

...................................................................................................... 822
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 3, 2006. Version 3.
Checksum: 4C2A90555857F045

FASTA82293,497
        10         20         30         40         50         60 
MGFSSELCSP QGHGVLQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS 

        70         80         90        100        110        120 
RAISPDSPIS QSWAEITSQT EGLSRLLRQH AEDLNSGPLS KLSLLIRERQ QLRKTYSEQW 

       130        140        150        160        170        180 
QQLQQELTKT HSQDIEKLKS QYRALARDSA QAKRKYQEAS KDKDRDKAKD KYVRSLWKLF 

       190        200        210        220        230        240 
AHHNRYVLGV RAAQLHHQHH HQLLLPGLLR SLQDLHEEMA CILKEILQEY LEISSLVQDE 

       250        260        270        280        290        300 
VVAIHREMAA AAARIQPEAE YQGFLRQYGS APDVPPCVTF DESLLEEGEP LEPGELQLNE 

       310        320        330        340        350        360 
LTVESVQHTL TSVTDELAVA TEMVFRRQEM VTQLQQELRN EEENTHPRER VQLLGKRQVL 

       370        380        390        400        410        420 
QEALQGLQVA LCSQAKLQAQ QELLQTKLEH LGPGEPPPVL LLQDDRHSTS SSEQEREGGR 

       430        440        450        460        470        480 
TPTLEILKSH ISGIFRPKFS LPPPLQLIPE VQKPLHEQLW YHGAIPRAEV AELLVHSGDF 

       490        500        510        520        530        540 
LVRESQGKQE YVLSVLWDGL PRHFIIQSLD NLYRLEGEGF PSIPLLIDHL LSTQQPLTKK 

       550        560        570        580        590        600 
SGVVLHRAVP KDKWVLNHED LVLGEQIGRG NFGEVFSGRL RADNTLVAVK SCRETLPPDL 

       610        620        630        640        650        660 
KAKFLQEARI LKQYSHPNIV RLIGVCTQKQ PIYIVMELVQ GGDFLTFLRT EGARLRVKTL 

       670        680        690        700        710        720 
LQMVGDAAAG MEYLESKCCI HRDLAARNCL VTEKNVLKIS DFGMSREEAD GVYAASGGLR 

       730        740        750        760        770        780 
QVPVKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGASP YPNLSNQQTR EFVEKGGRLP 

       790        800        810        820 
CPELCPDAVF RLMEQCWAYE PGQRPSFSTI YQELQSIRKR HR 

« Hide

Isoform 2 (Variant 1) [UniParc].

Checksum: 9BFFA652C8C3B8EB
Show »

FASTA69478,633
Isoform 3 (Variant 3) [UniParc].

Checksum: 3F3713631F1D08A2
Show »

FASTA76486,663
Isoform 4 (Variant 4) [UniParc].

Checksum: 0580B667FEF3FDD1
Show »

FASTA75285,466

References

« Hide 'large scale' references
[1]"Characterization of human and mouse c-fes cDNA clones and identification of the 5' end of the gene."
Alcalay M., Antolini F., van de Ven W.J.M., Lanfrancone L., Grignani F., Pelicci P.G.
Oncogene 5:267-275(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The structure of the human c-fes/fps proto-oncogene."
Roebroek A.J.M., Schalken J.A., Verbeek J.S., van den Ouweland A.M.W., Onnekink C., Bloemers H.P.J., van de Ven W.J.M.
EMBO J. 4:2897-2903(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]Lefebvre J.-C.
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Tongue.
[5]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[8]"K562 leukemia cells transfected with the human c-fes gene acquire the ability to undergo myeloid differentiation."
Yu G., Smithgall T.E., Glazer R.I.
J. Biol. Chem. 264:10276-10281(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL DIFFERENTIATION AND AS TUMOR SUPPRESSOR, CATALYTIC ACTIVITY.
[9]"Regulation of the human c-fes protein tyrosine kinase (p93c-fes) by its src homology 2 domain and major autophosphorylation site (Tyr-713)."
Hjermstad S.J., Peters K.L., Briggs S.D., Glazer R.I., Smithgall T.E.
Oncogene 8:2283-2292(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-713, CATALYTIC ACTIVITY, MUTAGENESIS OF TYR-713.
[10]"Co-expression with BCR induces activation of the FES tyrosine kinase and phosphorylation of specific N-terminal BCR tyrosine residues."
Li J., Smithgall T.E.
J. Biol. Chem. 271:32930-32936(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BCR, AUTOPHOSPHORYLATION, ENZYME REGULATION.
[11]"Subcellular localization analysis of the closely related Fps/Fes and Fer protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular trafficking."
Zirngibl R., Schulze D., Mirski S.E., Cole S.P., Greer P.A.
Exp. Cell Res. 266:87-94(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[12]"A point mutation in the N-terminal coiled-coil domain releases c-Fes tyrosine kinase activity and survival signaling in myeloid leukemia cells."
Cheng H.Y., Schiavone A.P., Smithgall T.E.
Mol. Cell. Biol. 21:6170-6180(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL PROLIFERATION AND CELL SPREADING, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, DOMAIN, MUTAGENESIS OF LEU-145 AND LEU-334.
[13]"Closing in on the biological functions of Fps/Fes and Fer."
Greer P.
Nat. Rev. Mol. Cell Biol. 3:278-289(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[14]"The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner."
Laurent C.E., Smithgall T.E.
Exp. Cell Res. 299:188-198(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REORGANIZATION OF THE ACTIN CYTOSKELETON AND CELL DIFFERENTIATION, INTERACTION WITH BCR.
[15]"The human c-Fes tyrosine kinase binds tubulin and microtubules through separate domains and promotes microtubule assembly."
Laurent C.E., Delfino F.J., Cheng H.Y., Smithgall T.E.
Mol. Cell. Biol. 24:9351-9358(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TUBULIN AND MICROTUBULES, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-713, PHOSPHORYLATION BY HCK, MUTAGENESIS OF LEU-145; ARG-483 AND LYS-590.
[16]"An identity crisis for fps/fes: oncogene or tumor suppressor?"
Sangrar W., Zirgnibl R.A., Gao Y., Muller W.J., Jia Z., Greer P.A.
Cancer Res. 65:3518-3522(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF MET-704; ARG-706; VAL-743 AND SER-759.
[17]"Expression of c-Fes protein isoforms correlates with differentiation in myeloid leukemias."
Carlson A., Berkowitz J.M., Browning D., Slamon D.J., Gasson J.C., Yates K.E.
DNA Cell Biol. 24:311-316(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[18]"The KRAB-associated co-repressor KAP-1 is a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase."
Delfino F.J., Shaffer J.M., Smithgall T.E.
Biochem. J. 399:141-150(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM28.
[19]"A growth-suppressive function for the c-fes protein-tyrosine kinase in colorectal cancer."
Delfino F.J., Stevenson H., Smithgall T.E.
J. Biol. Chem. 281:8829-8835(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN STAT3 PHOSPHORYLATION, ROLE AS PUTATIVE TUMOR SUPPRESSOR IN COLON CANCER, MUTAGENESIS OF MET-704; ARG-706; VAL-743 AND SER-759, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[20]"The tyrosine kinase FES is an essential effector of KITD816V proliferation signal."
Voisset E., Lopez S., Dubreuil P., De Sepulveda P.
Blood 110:2593-2599(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN KIT SIGNALING, POSSIBLE ROLE IN CANCER CELL PROLIFERATION.
[21]"Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering."
Naba A., Reverdy C., Louvard D., Arpin M.
EMBO J. 27:38-50(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CYTOSKELETON REORGANIZATION, INTERACTION WITH EZR, PHOSPHORYLATION AT TYR-713, SUBCELLULAR LOCATION.
[22]"Bimolecular fluorescence complementation demonstrates that the c-Fes protein-tyrosine kinase forms constitutive oligomers in living cells."
Shaffer J.M., Hellwig S., Smithgall T.E.
Biochemistry 48:4780-4788(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-713, PHOSPHORYLATION BY HCK, DOMAIN.
[23]"Promoter methylation blocks FES protein-tyrosine kinase gene expression in colorectal cancer."
Shaffer J.M., Smithgall T.E.
Genes Chromosomes Cancer 48:272-284(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, ROLE AS PUTATIVE TUMOR SUPPRESSOR IN COLON CANCER.
[24]"Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells."
Kanda S., Miyata Y., Kanetake H., Smithgall T.E.
Int. J. Oncol. 34:89-96(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PUTATIVE ROLE IN RENAL CARCINOMA.
[25]"Contributions of F-BAR and SH2 domains of Fes protein tyrosine kinase for coupling to the FcepsilonRI pathway in mast cells."
McPherson V.A., Everingham S., Karisch R., Smith J.A., Udell C.M., Zheng J., Jia Z., Craig A.W.
Mol. Cell. Biol. 29:389-401(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MS4A2/FCER1B AND HCLS1/HS1, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH PHOSPHOINOSITIDE-CONTAINING MEMBRANES, MUTAGENESIS OF 113-ARG-LYS-114.
[26]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-67; TYR-261; TYR-713 AND SER-716, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"FES kinases are required for oncogenic FLT3 signaling."
Voisset E., Lopez S., Chaix A., Georges C., Hanssens K., Prebet T., Dubreuil P., De Sepulveda P.
Leukemia 24:721-728(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT THR-421, INTERACTION WITH FLT3.
[28]"Structure and regulation of the c-Fes protein-tyrosine kinase."
Hellwig S., Smithgall T.E.
Front. Biosci. 16:3146-3155(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[29]"Pathological significance and predictive value for biochemical recurrence of c-Fes expression in prostate cancer."
Miyata Y., Watanabe S.I., Matsuo T., Hayashi T., Sakai H., Xuan J.W., Greer P.A., Kanda S.
Prostate 72:201-208(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE ROLE IN PROSTATE CANCER.
[30]"Solution structure of the Src homology 2 domain from the human feline sarcoma oncogene Fes."
Scott A., Pantoja-Uceda D., Koshiba S., Inoue M., Kigawa T., Terada T., Shirouzu M., Tanaka A., Sugano S., Yokoyama S., Guentert P.
J. Biomol. NMR 31:357-361(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 450-550.
[31]"Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation."
Filippakopoulos P., Kofler M., Hantschel O., Gish G.D., Grebien F., Salah E., Neudecker P., Kay L.E., Turk B.E., Superti-Furga G., Pawson T., Knapp S.
Cell 134:793-803(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 448-822 OF UNPHOSPHORYLATED APOPROTEIN AND IN COMPLEX WITH STAUROSPORINE AND A SUBSTRATE PEPTIDE, CATALYTIC ACTIVITY, ENZYME REGULATION, PHOSPHORYLATION AT TYR-713, NMR SPECTROSCOPY, MUTAGENESIS OF GLY-463 AND ARG-483.
[32]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-85; GLN-246 AND VAL-323.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X52192 mRNA. Translation: CAA36438.1.
X06292 Genomic DNA. Translation: CAA29619.1.
AY513654 mRNA. Translation: AAS82866.1.
AY513656 mRNA. Translation: AAS82868.1.
AY513657 mRNA. Translation: AAS82869.1.
AK300595 mRNA. Translation: BAG62292.1.
AK312545 mRNA. Translation: BAG35443.1.
AC124248 Genomic DNA. No translation available.
CH471101 Genomic DNA. Translation: EAX02114.1.
BC035357 mRNA. Translation: AAH35357.1.
CCDSCCDS10365.1. [P07332-1]
CCDS45349.1. [P07332-4]
CCDS45350.1. [P07332-3]
CCDS45351.1. [P07332-2]
PIRTVHUFF. A24673.
RefSeqNP_001137255.1. NM_001143783.1. [P07332-3]
NP_001137256.1. NM_001143784.1. [P07332-4]
NP_001137257.1. NM_001143785.1. [P07332-2]
NP_001996.1. NM_002005.3. [P07332-1]
XP_005254934.1. XM_005254877.1. [P07332-1]
XP_005254937.1. XM_005254880.1. [P07332-3]
XP_005254938.1. XM_005254881.1. [P07332-3]
XP_005254939.1. XM_005254882.1. [P07332-4]
UniGeneHs.7636.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WQUNMR-A450-550[»]
2DCRNMR-A450-550[»]
3BKBX-ray1.78A448-822[»]
3CBLX-ray1.75A448-822[»]
3CD3X-ray1.98A448-822[»]
4DYLX-ray2.18A1-405[»]
4E93X-ray1.84A448-822[»]
ProteinModelPortalP07332.
SMRP07332. Positions 1-402, 449-821.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108533. 22 interactions.
IntActP07332. 19 interactions.
MINTMINT-1497714.
STRING9606.ENSP00000331504.

Chemistry

BindingDBP07332.
ChEMBLCHEMBL5455.
GuidetoPHARMACOLOGY2023.

PTM databases

PhosphoSiteP07332.

Polymorphism databases

DMDM115502390.

Proteomic databases

MaxQBP07332.
PaxDbP07332.
PRIDEP07332.

Protocols and materials databases

DNASU2242.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328850; ENSP00000331504; ENSG00000182511. [P07332-1]
ENST00000394300; ENSP00000377837; ENSG00000182511. [P07332-3]
ENST00000414248; ENSP00000414629; ENSG00000182511. [P07332-2]
ENST00000444422; ENSP00000400868; ENSG00000182511. [P07332-4]
ENST00000450438; ENSP00000409915; ENSG00000182511. [P07332-2]
GeneID2242.
KEGGhsa:2242.
UCSCuc002bpv.3. human. [P07332-1]
uc002bpx.3. human. [P07332-4]
uc002bpy.3. human. [P07332-3]
uc010uqj.2. human. [P07332-2]

Organism-specific databases

CTD2242.
GeneCardsGC15P091426.
HGNCHGNC:3657. FES.
HPAHPA001376.
MIM190030. gene.
neXtProtNX_P07332.
PharmGKBPA28098.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG005655.
InParanoidP07332.
KOK07527.
OMAYQGFLRQ.
OrthoDBEOG708VXW.
PhylomeDBP07332.
TreeFamTF315363.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
SignaLinkP07332.

Gene expression databases

ArrayExpressP07332.
BgeeP07332.
CleanExHS_FES.
GenevestigatorP07332.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR001060. FCH_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR016250. Tyr-prot_kinase_Fes/Fps.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF00611. FCH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PIRSFPIRSF000632. TyrPK_fps. 1 hit.
PRINTSPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTSM00055. FCH. 1 hit.
SM00252. SH2. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50133. FCH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP07332.
GeneWikiFeline_sarcoma_oncogene.
GenomeRNAi2242.
NextBio9069.
PROP07332.
SOURCESearch...

Entry information

Entry nameFES_HUMAN
AccessionPrimary (citable) accession number: P07332
Secondary accession number(s): B2R6E6 expand/collapse secondary AC list , B4DUD0, E9PC94, E9PC95, Q2VXS7, Q2VXS8, Q2VXT0, Q6GTU5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: October 3, 2006
Last modified: July 9, 2014
This is version 165 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM