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P16591 (FER_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. 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 Fer

EC=2.7.10.2
Alternative name(s):
Feline encephalitis virus-related kinase FER
Fujinami poultry sarcoma/Feline sarcoma-related protein Fer
Proto-oncogene c-Fer
Tyrosine kinase 3
p94-Fer
Gene names
Name:FER
Synonyms:TYK3
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 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 synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. 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 depends on cell type and stimulus. Ref.2 Ref.9 Ref.10 Ref.11 Ref.12 Ref.16 Ref.18 Ref.20 Ref.21 Ref.22

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.11 Ref.20

Enzyme regulation

Activated by phosphatidic acid binding. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS). Ref.20

Subunit structure

Homotrimer. Interacts with ARHGDIA, IRS1, JAK1, NRP1, PIK3R1, PLEC and TMF1. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320' By similarity. 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. Ref.9 Ref.10 Ref.11 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22

Subcellular location

Cytoplasm. Cytoplasmcytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection. Cell junction. Membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. Cytoplasmcell cortex. 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. Ref.8 Ref.10 Ref.11 Ref.13

Tissue specificity

Isoform 1 is detected in normal colon and in fibroblasts (at protein level). Isoform 3 is detected in normal testis, in colon carcinoma-derived metastases in lung, liver and ovary, and in colon carcinoma and hepato carcinoma cell lines (at protein level). Isoform 3 is not detected in normal colon or in normal fibroblasts (at protein level). Widely expressed. Ref.2 Ref.7 Ref.14

Domain

The coiled coil domains mediate homooligomerization and are required for location at microtubules. Ref.13 Ref.20

The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes. Ref.13 Ref.20

Post-translational modification

Autophosphorylated. Ref.9 Ref.21 Ref.22

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
   Coding sequence diversityAlternative promoter usage
Alternative splicing
Polymorphism
   DiseaseProto-oncogene
   DomainCoiled coil
SH2 domain
   LigandATP-binding
Lipid-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete 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 mutant phenotype Ref.2. Source: UniProtKB

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 mutant phenotype Ref.10. Source: UniProtKB

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 mutant phenotype Ref.10. 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 mutant phenotype Ref.18. Source: UniProtKB

intracellular signal transduction

Traceable author statement PubMed 2209086. Source: ProtInc

microtubule cytoskeleton organization

Inferred from mutant phenotype Ref.11. Source: UniProtKB

mitotic cell cycle

Inferred from mutant phenotype Ref.2. Source: UniProtKB

negative regulation of mast cell activation involved in immune response

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.11Ref.20. 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 mutant phenotype Ref.22. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from mutant phenotype Ref.20. Source: UniProtKB

positive regulation of cell migration

Inferred from mutant phenotype Ref.20. Source: UniProtKB

positive regulation of cell proliferation

Traceable author statement Ref.21. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.9. Source: UniProtKB

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

regulation of epidermal growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.22. Source: UniProtKB

regulation of fibroblast migration

Inferred from electronic annotation. Source: Ensembl

regulation of lamellipodium assembly

Inferred from direct assay Ref.20. 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 direct assay Ref.18. Source: UniProtKB

   Cellular_componentcell cortex

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell projection

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

cytoskeleton

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.20. Source: UniProtKB

nucleus

Inferred from direct assay Ref.18. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

epidermal growth factor receptor binding

Inferred from direct assay Ref.22. Source: UniProtKB

lipid binding

Inferred from direct assay Ref.20. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.11Ref.20. Source: UniProtKB

protein tyrosine kinase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

chBcatO424862EBI-1380661,EBI-972394From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform 1 (identifier: P16591-1)

Also known as: p94;

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: P16591-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-175: Missing.
Isoform 3 (identifier: P16591-3)

Also known as: FerT; p47;

The sequence of this isoform differs from the canonical sequence as follows:
     1-369: Missing.
     370-412: LRCTEAKFSA...EEDARSVTSM → MEQKMKCPHC...PSTSEVHRDQ
Note: Produced by alternative promoter usage.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 822822Tyrosine-protein kinase Fer
PRO_0000088084

Regions

Domain1 – 5858FCH
Domain460 – 55091SH2
Domain563 – 816254Protein kinase
Nucleotide binding569 – 5779ATP By similarity
Region1 – 300300Important for interaction with membranes containing phosphoinositides
Coiled coil123 – 18563 Potential
Coiled coil301 – 39090 Potential

Sites

Active site6841Proton acceptor By similarity
Binding site5911ATP By similarity

Amino acid modifications

Modified residue4021Phosphotyrosine Ref.15 Ref.19
Modified residue4341Phosphoserine Ref.15 Ref.19
Modified residue6151Phosphotyrosine; by autocatalysis By similarity
Modified residue7141Phosphotyrosine; by autocatalysis

Natural variations

Alternative sequence1 – 369369Missing in isoform 3.
VSP_043846
Alternative sequence1 – 175175Missing in isoform 2.
VSP_041765
Alternative sequence370 – 41243LRCTE…SVTSM → MEQKMKCPHCKDQLESGFGS QSCKTCALMFSSEPSTSEVH RDQ in isoform 3.
VSP_043847
Natural variant1281V → F. Ref.26
Corresponds to variant rs35150210 [ dbSNP | Ensembl ].
VAR_041691
Natural variant4041E → Q in an ovarian Endometrioid carcinoma sample; somatic mutation. Ref.26
VAR_041692
Natural variant4121M → V. Ref.26
Corresponds to variant rs33940843 [ dbSNP | Ensembl ].
VAR_041693
Natural variant4391L → V. Ref.1 Ref.25 Ref.26
Corresponds to variant rs34499946 [ dbSNP | Ensembl ].
VAR_006282
Natural variant4431A → P. Ref.26
Corresponds to variant rs34259824 [ dbSNP | Ensembl ].
VAR_041694
Natural variant4601W → C in a lung small cell carcinoma sample; somatic mutation. Ref.26
VAR_041695
Natural variant5071I → T.
Corresponds to variant rs34204308 [ dbSNP | Ensembl ].
VAR_051695
Natural variant8131E → Q. Ref.26
Corresponds to variant rs56097357 [ dbSNP | Ensembl ].
VAR_041696

Experimental info

Mutagenesis4831R → Q: Abolishes kinase activity. Abolishes location at microtubules. Ref.11
Mutagenesis5911K → R: Abolishes kinase activity. Ref.10
Sequence conflict2191I → L in BAG61714. Ref.3
Sequence conflict2341S → N in BAG61714. Ref.3
Sequence conflict4261H → Q in BAG61714. Ref.3
Sequence conflict4471M → L in AEY69041. Ref.2
Sequence conflict4851S → G in AEY69041. Ref.2
Sequence conflict4921Y → H in AEY69041. Ref.2
Sequence conflict5051F → L in BAG61714. Ref.3
Sequence conflict5581L → F in AEY69041. Ref.2
Sequence conflict7301E → G in BAG61714. Ref.3

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (p94) [UniParc].

Last modified May 16, 2006. Version 2.
Checksum: BD42DF6C03419C76

FASTA82294,638
        10         20         30         40         50         60 
MGFGSDLKNS HEAVLKLQDW ELRLLETVKK FMALRIKSDK EYASTLQNLC NQVDKESTVQ 

        70         80         90        100        110        120 
MNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYIGVHQQ 

       130        140        150        160        170        180 
IEAEMIKVTK TELEKLKCSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM 

       190        200        210        220        230        240 
LHNQYVLALK GAQLHQNQYY DITLPLLLDS LQKMQEEMIK ALKGIFDEYS QITSLVTEEI 

       250        260        270        280        290        300 
VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 

       310        320        330        340        350        360 
TAESLQVMLK TLAEELMQTQ QMLLNKEEAV LELEKRIEES SETCEKKSDI VLLLSQKQAL 

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

       430        440        450        460        470        480 
FESIRHSIAG IIRSPKSALG SSALSDMISI SEKPLAEQDW YHGAIPRIEA QELLKKQGDF 

       490        500        510        520        530        540 
LVRESHGKPG EYVLSVYSDG QRRHFIIQYV DNMYRFEGTG FSNIPQLIDH HYTTKQVITK 

       550        560        570        580        590        600 
KSGVVLLNPI PKDKKWILSH EDVILGELLG KGNFGEVYKG TLKDKTSVAV KTCKEDLPQE 

       610        620        630        640        650        660 
LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPVYIIMELV SGGDFLTFLR RKKDELKLKQ 

       670        680        690        700        710        720 
LVKFSLDAAA GMLYLESKNC IHRDLAARNC LVGENNVLKI SDFGMSRQED GGVYSSSGLK 

       730        740        750        760        770        780 
QIPIKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGVCP YPGMTNQQAR EQVERGYRMS 

       790        800        810        820 
APQHCPEDIS KIMMKCWDYK PENRPKFSEL QKELTIIKRK LT 

« Hide

Isoform 2 [UniParc].

Checksum: F05F6497716D7D36
Show »

FASTA64774,266
Isoform 3 (FerT) (p47) [UniParc].

Checksum: E9B8AD1A2DD0A7DC
Show »

FASTA45351,643

References

« Hide 'large scale' references
[1]"Isolation and sequence analysis of a novel human tyrosine kinase gene."
Hao Q.-L., Heisterkamp N., Groffen J.
Mol. Cell. Biol. 9:1587-1593(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-439.
[2]"Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells."
Makovski A., Yaffe E., Shpungin S., Nir U.
J. Biol. Chem. 287:6100-6112(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE PROMOTER USAGE, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
Tissue: Testis.
[3]"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: Brain.
[4]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes."
Lee S.-T., Strunk K.M., Spritz R.A.
Oncogene 8:3403-3410(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 686-741.
[7]"Identification and chromosomal mapping of new human tyrosine kinase genes."
Krolewski J.J., Lee R., Eddy R., Shows T.B., Dalla-Favera R.
Oncogene 5:277-282(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Nuclear and cytoplasmic location of the FER tyrosine kinase."
Hao Q.-L., Ferris D.K., White G., Heisterkamp N., Groffen J.
Mol. Cell. Biol. 11:1180-1183(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors."
Kim L., Wong T.W.
Mol. Cell. Biol. 15:4553-4561(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CTNND1, AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH CTNND1.
[10]"Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the cytoplasmic tyrosine kinase FER."
Kim L., Wong T.W.
J. Biol. Chem. 273:23542-23548(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CTTN, INTERACTION WITH CTTN; CTNND1 AND PDGFR, MUTAGENESIS OF LYS-591, SUBCELLULAR LOCATION.
[11]"Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells."
Kogata N., Masuda M., Kamioka Y., Yamagishi A., Endo A., Okada M., Mochizuki N.
Mol. Biol. Cell 14:3553-3564(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PECAM1; PTPN11 AND GAB1, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-483, INTERACTION WITH PECAM1.
[12]"Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription."
Miravet S., Piedra J., Castano J., Raurell I., Franci C., Dunach M., Garcia de Herreros A.
Mol. Cell. Biol. 23:7391-7402(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF JUP AND IN REGULATION OF PROTEIN PHOSPHORYLATION.
[13]"Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis."
Tsujita K., Suetsugu S., Sasaki N., Furutani M., Oikawa T., Takenawa T.
J. Cell Biol. 172:269-279(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, LIPID-BINDING, DOMAIN.
[14]"Expression of Fer testis (FerT) tyrosine kinase transcript variants and distribution sites of FerT during the development of the acrosome-acroplaxome-manchette complex in rat spermatids."
Kierszenbaum A.L., Rivkin E., Tres L.L.
Dev. Dyn. 237:3882-3891(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION OF ISOFORM 3, TISSUE SPECIFICITY.
[15]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402 AND SER-434, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes."
Oh M.A., Choi S., Lee M.J., Choi M.C., Lee S.A., Ko W., Cance W.G., Oh E.S., Buday L., Kim S.H., Lee J.W.
Biochim. Biophys. Acta 1793:781-791(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PTK2/FAK1, FUNCTION IN REGULATION OF ACTIN CYTOSKELETON, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH CTTN AND PTK2/FAK1.
[17]"Hsp90 and a tyrosine embedded in the Hsp90 recognition loop are required for the Fer tyrosine kinase activity."
Hikri E., Shpungin S., Nir U.
Cell. Signal. 21:588-596(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HSP90.
[18]"The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth."
Zoubeidi A., Rocha J., Zouanat F.Z., Hamel L., Scarlata E., Aprikian A.G., Chevalier S.
Mol. Cancer Res. 7:142-155(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN IL6 SIGNALING PATHWAY; CELL PROLIFERATION AND IN PHOSPHORYLATION OF STAT3, INTERACTION WITH STAT3.
[19]"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 TYR-402 AND SER-434, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration."
Itoh T., Hasegawa J., Tsujita K., Kanaho Y., Takenawa T.
Sci. Signal. 2:RA52-RA52(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF ACTIN CYTOSKELETON AND CELL MIGRATION, CATALYTIC ACTIVITY, DOMAIN, LIPID-BINDING, ENZYME REGULATION.
[21]"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 IN CELL PROLIFERATION, PHOSPHORYLATION, INTERACTION WITH FLT3.
[22]"FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-kappaB."
Guo C., Stark G.R.
Proc. Natl. Acad. Sci. U.S.A. 108:7968-7973(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF NF-KAPPA-B DOWNSTREAM OF EGFR AND CELL PROLIFERATION, INTERACTION WITH EGFR, PHOSPHORYLATION.
[23]"Solution structure of SH2 domain of proto-oncogene tyrosine-protein kinase FER from Homo sapiens, Northeast structural genomics consortium (NESG) target HR3461D."
Northeast structural genomics consortium (NESG)
Submitted (AUG-2009) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 453-557.
[24]"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.
[25]"Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients."
Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P., Markham A., Krush A.J., Petersen G.M., Hamilton S.R., Nilbert M.C., Levy D.B., Bryan T.M., Preisinger A.C. expand/collapse author list , Smith K.J., Su L.-K., Kinzler K.W., Vogelstein B.
Science 253:665-669(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VAL-439.
[26]"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] PHE-128; GLN-404; VAL-412; VAL-439; PRO-443; CYS-460 AND GLN-813.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03358 mRNA. Translation: AAA61190.1.
JQ412173 mRNA. Translation: AEY69041.1.
AK299855 mRNA. Translation: BAG61714.1.
AK315234 mRNA. Translation: BAG37661.1.
AC034207 Genomic DNA. No translation available.
AC008871 Genomic DNA. No translation available.
AC109481 Genomic DNA. No translation available.
AC008955 Genomic DNA. No translation available.
AC010228 Genomic DNA. No translation available.
AC011421 Genomic DNA. No translation available.
AC116428 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW49055.1.
PIRTVHUFE. A31943.
RefSeqNP_005237.2. NM_005246.2.
UniGeneHs.221472.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KK6NMR-A453-557[»]
ProteinModelPortalP16591.
SMRP16591. Positions 1-400, 452-820.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108532. 13 interactions.
IntActP16591. 10 interactions.
MINTMINT-261636.
STRING9606.ENSP00000281092.

Chemistry

BindingDBP16591.
ChEMBLCHEMBL3982.
GuidetoPHARMACOLOGY2022.

PTM databases

PhosphoSiteP16591.

Polymorphism databases

DMDM97536202.

Proteomic databases

PaxDbP16591.
PeptideAtlasP16591.
PRIDEP16591.

Protocols and materials databases

DNASU2241.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000281092; ENSP00000281092; ENSG00000151422. [P16591-1]
ENST00000438717; ENSP00000394297; ENSG00000151422. [P16591-2]
GeneID2241.
KEGGhsa:2241.
UCSCuc003kop.1. human. [P16591-1]
uc031skp.1. human. [P16591-3]

Organism-specific databases

CTD2241.
GeneCardsGC05P108111.
HGNCHGNC:3655. FER.
HPACAB022464.
HPA007641.
MIM176942. gene.
neXtProtNX_P16591.
PharmGKBPA28095.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000059550.
HOVERGENHBG005655.
InParanoidP16591.
KOK08889.
OMAFVDNLYR.
OrthoDBEOG708VXW.
PhylomeDBP16591.
TreeFamTF315363.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111102. Signal Transduction.
SignaLinkP16591.

Gene expression databases

ArrayExpressP16591.
BgeeP16591.
CleanExHS_FER.
GenevestigatorP16591.

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:SF86. PTHR24418:SF86. 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

EvolutionaryTraceP16591.
GeneWikiFER_(gene).
GenomeRNAi2241.
NextBio9065.
PROP16591.
SOURCESearch...

Entry information

Entry nameFER_HUMAN
AccessionPrimary (citable) accession number: P16591
Secondary accession number(s): B2RCR4, B4DSQ2, H2FLB8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: May 16, 2006
Last modified: April 16, 2014
This is version 156 of the entry and version 2 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 5

Human chromosome 5: entries, gene names and cross-references to MIM