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P14238 (FES_FELCA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
OrganismFelis catus (Cat) (Felis silvestris catus) [Reference proteome]
Taxonomic identifier9685 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraFeliformiaFelidaeFelinaeFelis

Protein attributes

Sequence length820 AA.
Sequence statusComplete.
Protein existenceInferred from homology

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 By similarity.

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-711. Present in an inactive form in the absence of activating stimuli By similarity.

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.

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-711 in response to FGF2. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK By similarity.

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
SH2 domain
   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

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

Inferred from electronic annotation. Source: UniProtKB-SubCell

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 tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 820820Tyrosine-protein kinase Fes/Fps
PRO_0000088085

Regions

Domain1 – 9494FCH
Domain458 – 54790SH2
Domain559 – 820262Protein kinase
Nucleotide binding565 – 5739ATP By similarity
Region1 – 298298Important for interaction with membranes containing phosphoinositides By similarity
Coiled coil123 – 16341 Potential
Coiled coil318 – 38972 Potential

Sites

Active site6811Proton acceptor By similarity
Binding site5881ATP By similarity

Amino acid modifications

Modified residue651Phosphoserine By similarity
Modified residue2591Phosphotyrosine By similarity
Modified residue4191Phosphothreonine By similarity
Modified residue7111Phosphotyrosine; by autocatalysis By similarity
Modified residue7141Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
P14238 [UniParc].

Last modified February 1, 1996. Version 2.
Checksum: F3A52B750236834E

FASTA82092,975
        10         20         30         40         50         60 
MGFSSELCSP QGHGAVQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDGGGRG 

        70         80         90        100        110        120 
TGPYSPISQS WAEITSQTEG LSRLLRQHAE DLNSGPLSKL GLLIRERQQL RKTYSEQWQQ 

       130        140        150        160        170        180 
LQQELTKTHN QDIEKLKSQY RALARDSAQA RRKYQEASKD KDRDKAKDKY VRSLWKLFAH 

       190        200        210        220        230        240 
HNRYVLGVRA AQLHHHHHHQ LMLPGLLQSL QDLHQEMACI LKEILQEYLE ISSLVQDEVV 

       250        260        270        280        290        300 
AIHLEMAAAV ARIQPEAEYQ GFLRQYGSTP DVPPCVTFDE SLLEEGEPLE PGELQLNELT 

       310        320        330        340        350        360 
VESVQHTLTS VTDELTVATQ TVLSRQEAVA QLQRELQNEE QNTHPRERVQ LLAKKQVLQE 

       370        380        390        400        410        420 
ALQALQVALC SQAKLQAQRE LLQAKLEQLG PGEPPPVLLL QDDRHSTSSS EQEREGGRTP 

       430        440        450        460        470        480 
TLEILKSHIS GIFRPKFSLP PPLQLVPEVQ KPLHEQLWYH GALPRAEVAE LLTHSGDFLV 

       490        500        510        520        530        540 
RESQGKQEYV LSVLWDGQPR HFIIESADNL YRLEGDGFAS IPLLVDHLLR SQQPLTKKSG 

       550        560        570        580        590        600 
IVLNRAVPKD KWVLNHEDLV LGEQIGRGNF GEVFSGRLRA DNTLVAVKSC RETLPPDIKA 

       610        620        630        640        650        660 
KFLQEAKILK QYSHPNIVRL IGVCTQKQPI YIVMELVQGG DFLTFLRTEG ARLRMKTLLQ 

       670        680        690        700        710        720 
MVGDAAAGME YLESKCCIHR DLAARNCLVT EKNVLKISDF GMSREEADGI YAASGGLRQV 

       730        740        750        760        770        780 
PVKWTAPEAL NYGRYSSESD VWSFGILLWE TFSLGASPYP NLSNQQTREF VEKGGRLPCP 

       790        800        810        820 
ELCPDAVFRL MEQCWAYEPG QRPSFSAIYQ ELQSIRKRHR 

« Hide

References

[1]"Structure of the feline c-fes/fps proto-oncogene: genesis of a retroviral oncogene."
Roebroek A.J.M., Schalken J.A., Onnekink C., Bloemers H.P.J., van de Ven W.J.M.
J. Virol. 61:2009-2016(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M16705 expand/collapse EMBL AC list , M16666, M16667, M16668, M16669, M16670, M16671, M16706, M16672, M16673, M16674, M16698, M16700, M16701, M16702, M16704 Genomic DNA. Translation: AAA30808.1.
PIRTVCTFF. A27824.

3D structure databases

ProteinModelPortalP14238.
SMRP14238. Positions 447-819.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9685.ENSFCAP00000005663.

Proteomic databases

PRIDEP14238.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG005655.

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...

Entry information

Entry nameFES_FELCA
AccessionPrimary (citable) accession number: P14238
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: February 1, 1996
Last modified: June 11, 2014
This is version 112 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