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P16879 (FES_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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):
Proto-oncogene c-Fes
Gene names
Name:Fes
Synonyms:Fps
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.7 Ref.8 Ref.10

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. Ref.7

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 By similarity. Ref.8

Subcellular location

Cytoplasmcytosol By similarity. Cytoplasmcytoskeleton By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmic vesicle By similarity. Golgi apparatus By similarity. Cell junctionfocal adhesion By similarity. 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 By similarity.

Domain

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

The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes By similarity.

Post-translational modification

Autophosphorylated on Tyr-713 in response to FGF2. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK By similarity. Ref.7 Ref.8

Disruption phenotype

No visible phenotype. Mice are fertile and healthy, display slightly reduced numbers of myeloid cells and are more sensitive to lipopolysaccharide (LPS). Mice lacking both Fps/Fes and Fer activity are viable and fertile, but produce fewer offspring than normal. They display elevated levels of circulating neutrophils, erythrocytes and platelets, while other cell counts are normal. Ref.2 Ref.6

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
   DiseaseProto-oncogene
Tumor suppressor
   DomainCoiled coil
   LigandATP-binding
Lipid-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processpeptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of actin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of microtubule polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of myeloid cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell motility

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mast cell degranulation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB

focal adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

microtubule cytoskeleton

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

immunoglobulin receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase activity

Inferred from direct assay PubMed 12192036. Source: MGI

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

H2-K1P019013EBI-771815,EBI-1265227
Ptpn11P352352EBI-771815,EBI-397236

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 822822Tyrosine-protein kinase Fes/Fps
PRO_0000088089

Regions

Domain1 – 9696FCH
Domain460 – 54990SH2
Domain561 – 818258Protein kinase
Nucleotide binding567 – 5759ATP By similarity
Region1 – 300300Important for interaction with membranes containing phosphoinositides By similarity
Coiled coil133 – 16533 Potential
Coiled coil320 – 36950 Potential

Sites

Active site6831Proton acceptor By similarity
Binding site5901ATP By similarity

Amino acid modifications

Modified residue671Phosphoserine By similarity
Modified residue2611Phosphotyrosine By similarity
Modified residue4211Phosphothreonine By similarity
Modified residue7131Phosphotyrosine; by autocatalysis Ref.9
Modified residue7161Phosphoserine By similarity

Experimental info

Sequence conflict110 – 1112QH → HS in CAA31138. Ref.1
Sequence conflict413 – 4142Missing in CAA31138. Ref.1
Sequence conflict413 – 4142Missing in AAN33122. Ref.2
Sequence conflict4671R → W in CAA31138. Ref.1
Sequence conflict4771S → T in CAA31138. Ref.1
Sequence conflict4771S → T in AAN33122. Ref.2
Sequence conflict5001Q → H in CAA31138. Ref.1
Sequence conflict5001Q → H in AAN33122. Ref.2
Sequence conflict5091S → L in CAA31138. Ref.1
Sequence conflict5091S → L in AAN33122. Ref.2
Sequence conflict6641V → M in CAA31138. Ref.1
Sequence conflict716 – 7172SA → CS in CAA31138. Ref.1
Sequence conflict716 – 7172SA → CS in AAA40012. Ref.5
Sequence conflict7491L → P in AAA40012. Ref.5

Sequences

Sequence LengthMass (Da)Tools
P16879 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: 939280C56ACF25EE

FASTA82293,779
        10         20         30         40         50         60 
MGFSSELCSP QGHGAVQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS 

        70         80         90        100        110        120 
WSSGPDSPVS QSWAEITSQT ENLSRVLRQH AEDLNSGPLS KLSVLIRERQ HLRKTYNEQW 

       130        140        150        160        170        180 
QQLQQELTKT HSQDIEKLKT QYRTLVRDST QARRKYQEAS KDKDRDKAKD KYVRSLWKLF 

       190        200        210        220        230        240 
AHHNRYVLGV RAAQLHHHHH HRFMLPGLLQ SLQDLHEEMA GILKDILQEY LEISSLVQDD 

       250        260        270        280        290        300 
VASIHRELAA AAARIQPEFE YLGFLRQYGS TPDVPPCVTF DESLLEDGEQ LEPGELQLNE 

       310        320        330        340        350        360 
LTLESVQHTL TSVTDELAVA TKEVLSRQEM VSQLQRELQS EEQNTHPRER VQLLSKRQML 

       370        380        390        400        410        420 
QEAIQGLQIA LCSQDKLQAQ QELLQSKMEQ LGTGEPPAVP LLQDDRHSTS STEQEREGGR 

       430        440        450        460        470        480 
TPTLEILKSH FSGIFRPKFS IPPPLQLVPE VQKPLYEQLW YHGAIPRAEV AELLTHSGDF 

       490        500        510        520        530        540 
LVRESQGKQE YVLSVMWDGQ PRHFIIQSSD NLYRLEGDGF PSIPLLITHL LSSQQPLTKK 

       550        560        570        580        590        600 
SGVVLFRAVP KDKWVLKHED LVLGEQIGRG NFGEVFSGRL RADNTPVAVK SCRETLPPDL 

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

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

       730        740        750        760        770        780 
QVPVKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGASP YPNLTNQQTR EFVEKGHRLP 

       790        800        810        820 
CPELCPDAVF RLMEQCWAYE PGQRPSFSII CQELHSIRKR HR 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and structural analysis of murine c-fes cDNA clones."
Wilks A.F., Kurban R.R.
Oncogene 3:289-294(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Enhanced endotoxin sensitivity in fps/fes-null mice with minimal defects in hematopoietic homeostasis."
Zirngibl R.A., Senis Y., Greer P.A.
Mol. Cell. Biol. 22:2472-2486(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE.
Strain: 129/SvJ.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Spleen.
[4]"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].
[5]"The application of the polymerase chain reaction to cloning members of the protein tyrosine kinase family."
Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J.
Gene 85:67-74(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 680-749.
[6]"Fps/Fes and Fer protein-tyrosine kinases play redundant roles in regulating hematopoiesis."
Senis Y.A., Craig A.W., Greer P.A.
Exp. Hematol. 31:673-681(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[7]"Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation."
Udell C.M., Samayawardhena L.A., Kawakami Y., Kawakami T., Craig A.W.
J. Biol. Chem. 281:20949-20957(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MAST CELL ACTIVATION AND PHOSPHORYLATION OF PECAM1, PHOSPHORYLATION, ENZYME REGULATION.
[8]"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, INTERACTION WITH KIT, PHOSPHORYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
[9]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-713, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[10]"Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and beta1 integrin receptors."
Smith J.A., Samayawardhena L.A., Craig A.W.
Cell. Signal. 22:427-436(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X12616 mRNA. Translation: CAA31138.1.
AF542394 Genomic DNA. Translation: AAN33122.1.
M33421 mRNA. Translation: AAA40012.1.
AK143639 mRNA. Translation: BAE25475.1.
AK170418 mRNA. Translation: BAE41784.1.
BC129919 mRNA. Translation: AAI29920.1.
PIRI48347.
RefSeqNP_034324.2. NM_010194.2.
XP_006540667.1. XM_006540604.1.
UniGeneMm.48757.

3D structure databases

ProteinModelPortalP16879.
SMRP16879. Positions 1-402, 449-821.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199634. 1 interaction.
IntActP16879. 3 interactions.
MINTMINT-1520684.

PTM databases

PhosphoSiteP16879.

Proteomic databases

PRIDEP16879.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000080932; ENSMUSP00000079733; ENSMUSG00000053158.
GeneID14159.
KEGGmmu:14159.
UCSCuc009ias.1. mouse.

Organism-specific databases

CTD2242.
MGIMGI:95514. Fes.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117264.
HOGENOMHOG000059550.
HOVERGENHBG005655.
InParanoidP16879.
KOK07527.
OMAWDGQPRH.
OrthoDBEOG708VXW.
PhylomeDBP16879.
TreeFamTF315363.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.
ReactomeREACT_188576. Developmental Biology.

Gene expression databases

BgeeP16879.
CleanExMM_FES.
GenevestigatorP16879.

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]
PANTHERPTHR24418:SF85. PTHR24418:SF85. 1 hit.
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

NextBio285286.
PROP16879.
SOURCESearch...

Entry information

Entry nameFES_MOUSE
AccessionPrimary (citable) accession number: P16879
Secondary accession number(s): Q3TD20, Q62122, Q8CG02
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: January 15, 2008
Last modified: April 16, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot