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P09760 (FER_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 131. 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 Fer

EC=2.7.10.2
Alternative name(s):
Proto-oncogene c-Fer
Tyrosine-protein kinase FLK
p94-Fer
Gene names
Name:Fer
Synonyms:Fert2, Flk
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length823 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this clearly depends on cell type and stimulus By similarity. Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Ref.3

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Subunit structure

Homotrimer. Interacts with IRS1, JAK1, NRP1, PIK3R1, PLEC and TMF1. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320'. Interacts with CTNND1, EGFR, FLT3, PECAM1, PDGFR and STAT3. Interacts (via SH2 domain) with CTTN. Interacts with HSP90; this stabilizes phosphorylated FER and protects FER against proteasomal degradation. Component of a complex that contains at least FER, CTTN and PTK2/FAK1 By similarity. Interacts with ARHGDIA. Ref.4

Subcellular location

Cytoplasm By similarity. Cytoplasmcytoskeleton By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cell projection By similarity. Cell junction By similarity. Membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Nucleus By similarity. Cytoplasmcell cortex By similarity. Note: Associated with the chromatin. Detected on microtubules in polarized and motile vascular endothelial cells. Colocalizes with F-actin at the cell cortex. Colocalizes with PECAM1 and CTNND1 at nascent cell-cell contacts By similarity.

Domain

The coiled coil domains mediate homooligomerization and are required for location at microtubules By similarity.

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

Post-translational modification

Autophosphorylated By similarity.

Polyubiquitinated; this leads to proteasomal degradation 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
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Nucleus
   DomainCoiled coil
SH2 domain
   LigandATP-binding
Lipid-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

Kit signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

actin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from electronic annotation. Source: Ensembl

cell-cell adhesion mediated by cadherin

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to insulin stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to macrophage colony-stimulating factor stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to reactive oxygen species

Inferred from sequence or structural similarity. Source: UniProtKB

chemotaxis

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

diapedesis

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular matrix-cell signaling

Inferred from sequence or structural similarity. Source: UniProtKB

insulin receptor signaling pathway via phosphatidylinositol 3-kinase

Inferred from sequence or structural similarity. Source: UniProtKB

interleukin-6-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

microtubule cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of mast cell activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

platelet-derived growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of epidermal growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of fibroblast migration

Inferred from electronic annotation. Source: Ensembl

regulation of lamellipodium assembly

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

response to lipopolysaccharide

Inferred from sequence or structural similarity. Source: UniProtKB

response to platelet-derived growth factor

Inferred from sequence or structural similarity. Source: UniProtKB

substrate adhesion-dependent cell spreading

Inferred from sequence or structural similarity. Source: UniProtKB

tyrosine phosphorylation of Stat3 protein

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentactin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cell cortex

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

extrinsic component of cytoplasmic side of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium

Inferred from electronic annotation. Source: Ensembl

microtubule cytoskeleton

Inferred from electronic annotation. Source: Ensembl

nuclear chromatin

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Rab GTPase binding

Inferred from physical interaction PubMed 12700184. Source: RGD

actin binding

Inferred from physical interaction PubMed 12700184. Source: RGD

cadherin binding

Inferred from physical interaction PubMed 12700184. Source: RGD

cell adhesion molecule binding

Inferred from physical interaction PubMed 12700184. Source: RGD

cytoskeletal protein binding

Inferred from physical interaction PubMed 12700184. Source: RGD

epidermal growth factor receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

gamma-catenin binding

Inferred from physical interaction PubMed 12700184. Source: RGD

lipid binding

Inferred from sequence or structural similarity. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase binding

Inferred from physical interaction PubMed 12700184. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 823823Tyrosine-protein kinase Fer
PRO_0000088093

Regions

Domain1 – 5858FCH
Domain461 – 55191SH2
Domain564 – 815252Protein kinase
Nucleotide binding570 – 5789ATP By similarity
Region1 – 300300Important for interaction with membranes containing phosphoinositides By similarity
Coiled coil123 – 18563 Potential
Coiled coil301 – 38282 Potential

Sites

Active site6851Proton acceptor By similarity
Binding site5921ATP By similarity

Amino acid modifications

Modified residue4021Phosphotyrosine By similarity
Modified residue4341Phosphoserine By similarity
Modified residue6161Phosphotyrosine; by autocatalysis By similarity
Modified residue7151Phosphotyrosine; by autocatalysis By similarity

Experimental info

Sequence conflict5011G → R in CAA31778. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P09760 [UniParc].

Last modified September 21, 2011. Version 2.
Checksum: CA4F31E375F747DA

FASTA82394,314
        10         20         30         40         50         60 
MGFGSDLKNS QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC NQVDKDSTVQ 

        70         80         90        100        110        120 
VNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYVGIHQQ 

       130        140        150        160        170        180 
IEAEMIKVTK TELEKLKSSY RQLIKEMNSA KEKYKEALAK GKETEKAKER CDKATMKLHM 

       190        200        210        220        230        240 
LHNQYVLALK GAQLHQSQYY DTTLPLLLDS VQKMQEEMIK ALKGIFDEYS EITSLVTEEI 

       250        260        270        280        290        300 
VNVHKEIQMS VDQIDPSTEY NDFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 

       310        320        330        340        350        360 
TADSLQVMLK TLAEELTQTQ QMLLHKEAAV LELEKRIEES SETCAKKSDI VLLLGQKQAL 

       370        380        390        400        410        420 
EELKQSVQQL RCTEAKCAAQ KELLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK 

       430        440        450        460        470        480 
FESIRHSIAG IIKSPKSVLG SSTQLSDVIS VGEKPLAEHD WYHGAIPRIE AQELLKQQGD 

       490        500        510        520        530        540 
FLVRESHGKP GEYVLSVYSD GQRRHFIIQF VDNLYRFEGT GFSNIPQLID HHFNTKQVIT 

       550        560        570        580        590        600 
KKSGVVLLNP IPKDKKWVLN HEDVSLGELL GKGNFGEVYK GTLKDKTPVA VKTCKEDLPQ 

       610        620        630        640        650        660 
ELKIKFLQEA KILKQYDHPN IVKLIGVCTQ RQPVYIIMEL VPGGDFLSFL RKRKDELKLK 

       670        680        690        700        710        720 
QLVRFSLDVA AGMLYLEGKN CIHRDLAARN CLVGENNTLK ISDFGMSRQE DGGVYSSSGL 

       730        740        750        760        770        780 
KQIPIKWTAP EALNYGRYSS ESDVWSFGIL LWETFSLGVC PYPGMTNQQA REQVERGYRM 

       790        800        810        820 
SAPQNCPEEI FTIMMKCWDY KPENRPKFSD LHKELTAIKK KIT 

« Hide

References

« Hide 'large scale' references
[1]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[2]"Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned using anti-phosphotyrosine antibody."
Letwin K., Yee S.P., Pawson T.
Oncogene 3:621-627(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 501-823.
Strain: Wistar.
Tissue: Brain.
[3]"Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and beta-catenin."
Lee S.H., Peng I.F., Ng Y.G., Yanagisawa M., Bamji S.X., Elia L.P., Balsamo J., Lilien J., Anastasiadis P.Z., Ullian E.M., Reichardt L.F.
J. Cell Biol. 183:893-908(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SYNAPSE ORGANIZATION AND SYNAPTIC TRANSMISSION.
[4]"The Fer tyrosine kinase regulates interactions of Rho GDP-Dissociation Inhibitor alpha with the small GTPase Rac."
Fei F., Kweon S.M., Haataja L., De Sepulveda P., Groffen J., Heisterkamp N.
BMC Biochem. 11:48-48(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARHGDIA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X13412 mRNA. Translation: CAA31778.1.
PIRS04328.
RefSeqXP_006245662.1. XM_006245600.1.
UniGeneRn.102629.

3D structure databases

ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000021758.

PTM databases

PhosphoSiteP09760.

Proteomic databases

PaxDbP09760.
PRIDEP09760.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000021758; ENSRNOP00000021758; ENSRNOG00000015898.
GeneID301737.
KEGGrno:301737.

Organism-specific databases

CTD14158.
RGD1306273. Fert2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117264.
HOGENOMHOG000233858.
HOVERGENHBG001540.
InParanoidP09760.
KOK08889.
OMAFVDNLYR.
OrthoDBEOG708VXW.
TreeFamTF315363.

Gene expression databases

GenevestigatorP09760.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR001060. FCH_dom.
IPR028539. Fer.
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:SF227. PTHR24418:SF227. 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

PROP09760.

Entry information

Entry nameFER_RAT
AccessionPrimary (citable) accession number: P09760
Secondary accession number(s): F1MA12
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: September 21, 2011
Last modified: June 11, 2014
This is version 131 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