Tyrosine-protein kinase Fer

Details

Name
Tyrosine-protein kinase Fer
Synonyms
  • 2.7.10.2
  • Feline encephalitis virus-related kinase FER
  • Fujinami poultry sarcoma/Feline sarcoma-related protein Fer
  • p94-Fer
  • Proto-oncogene c-Fer
  • TYK3
  • Tyrosine kinase 3
Gene Name
FER
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051764|Tyrosine-protein kinase Fer
MGFGSDLKNSHEAVLKLQDWELRLLETVKKFMALRIKSDKEYASTLQNLCNQVDKESTVQ
MNYVSNVSKSWLLMIQQTEQLSRIMKTHAEDLNSGPLHRLTMMIKDKQQVKKSYIGVHQQ
IEAEMIKVTKTELEKLKCSYRQLIKEMNSAKEKYKEALAKGKETEKAKERYDKATMKLHM
LHNQYVLALKGAQLHQNQYYDITLPLLLDSLQKMQEEMIKALKGIFDEYSQITSLVTEEI
VNVHKEIQMSVEQIDPSTEYNNFIDVHRTTAAKEQEIEFDTSLLEENENLQANEIMWNNL
TAESLQVMLKTLAEELMQTQQMLLNKEEAVLELEKRIEESSETCEKKSDIVLLLSQKQAL
EELKQSVQQLRCTEAKFSAQKELLEQKVQENDGKEPPPVVNYEEDARSVTSMERKERLSK
FESIRHSIAGIIRSPKSALGSSALSDMISISEKPLAEQDWYHGAIPRIEAQELLKKQGDF
LVRESHGKPGEYVLSVYSDGQRRHFIIQYVDNMYRFEGTGFSNIPQLIDHHYTTKQVITK
KSGVVLLNPIPKDKKWILSHEDVILGELLGKGNFGEVYKGTLKDKTSVAVKTCKEDLPQE
LKIKFLQEAKILKQYDHPNIVKLIGVCTQRQPVYIIMELVSGGDFLTFLRRKKDELKLKQ
LVKFSLDAAAGMLYLESKNCIHRDLAARNCLVGENNVLKISDFGMSRQEDGGVYSSSGLK
QIPIKWTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVERGYRMS
APQHCPEDISKIMMKCWDYKPENRPKFSELQKELTIIKRKLT
Number of residues
822
Molecular Weight
94637.255
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / epidermal growth factor receptor binding / lipid binding / non-membrane spanning protein tyrosine kinase activity / protein phosphatase 1 binding / protein tyrosine kinase activity
Processes
actin cytoskeleton reorganization / cell adhesion / cell differentiation / cell proliferation / cell-cell adhesion mediated by cadherin / cellular response to insulin stimulus / cellular response to macrophage colony-stimulating factor stimulus / cellular response to reactive oxygen species / chemotaxis / cytokine-mediated signaling pathway / diapedesis / extracellular matrix-cell signaling / Fc-epsilon receptor signaling pathway / innate immune response / insulin receptor signaling pathway via phosphatidylinositol 3-kinase / interleukin-6-mediated signaling pathway / intracellular signal transduction / Kit signaling pathway / microtubule cytoskeleton organization / mitotic cell cycle / negative regulation of mast cell activation involved in immune response / peptidyl-tyrosine autophosphorylation / peptidyl-tyrosine phosphorylation / platelet-derived growth factor receptor signaling pathway / positive regulation of actin filament polymerization / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of NF-kappaB transcription factor activity / protein autophosphorylation / protein phosphorylation / regulation of epidermal growth factor receptor signaling pathway / regulation of fibroblast migration / regulation of lamellipodium assembly / regulation of mast cell degranulation / regulation of protein phosphorylation / response to lipopolysaccharide / response to platelet-derived growth factor / substrate adhesion-dependent cell spreading / tyrosine phosphorylation of STAT protein
Components
cell cortex / cell junction / cell projection / cytoplasm / cytoskeleton / cytosol / extrinsic component of cytoplasmic side of plasma membrane / nucleus
General 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.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051765|Tyrosine-protein kinase Fer (FER)
ATGGGGTTTGGGAGTGACCTGAAGAATTCACATGAAGCAGTGTTAAAATTGCAAGACTGG
GAATTACGGTTACTGGAAACAGTAAAGAAATTTATGGCCCTGAGAATAAAAAGTGATAAA
GAATATGCATCTACTTTACAGAACCTTTGTAATCAAGTTGATAAGGAAAGTACTGTCCAA
ATGAATTATGTCAGCAACGTATCCAAGTCTTGGCTACTTATGATTCAGCAGACAGAACAA
CTTAGTAGGATAATGAAGACACATGCAGAGGACTTGAACTCTGGACCTTTACACAGGCTC
ACCATGATGATTAAGGACAAGCAGCAGGTGAAGAAAAGTTACATAGGTGTTCATCAGCAG
ATAGAGGCAGAGATGATCAAGGTTACCAAAACAGAATTGGAGAAGTTAAAATGCAGCTAT
AGACAATTAATAAAAGAAATGAATTCTGCCAAAGAGAAATATAAAGAAGCTTTAGCTAAA
GGGAAGGAAACTGAAAAGGCCAAGGAACGATACGACAAAGCCACAATGAAACTTCATATG
TTGCACAATCAGTATGTATTGGCGTTGAAAGGGGCACAGCTCCATCAGAATCAGTATTAT
GATATCACACTTCCCCTGCTTCTGGACTCCTTACAAAAGATGCAAGAAGAAATGATAAAA
GCACTCAAAGGTATATTTGATGAATACAGCCAGATAACCAGTCTTGTCACAGAGGAAATA
GTGAATGTCCATAAAGAGATTCAAATGTCGGTTGAACAGATAGATCCTAGTACAGAATAC
AATAATTTCATAGATGTTCACAGAACAACGGCTGCTAAAGAACAAGAAATAGAGTTTGAT
ACTTCCTTACTGGAAGAAAATGAAAATCTTCAGGCAAATGAGATCATGTGGAATAACTTA
ACAGCAGAAAGTTTGCAAGTAATGTTGAAAACGTTAGCGGAAGAACTTATGCAAACACAG
CAGATGCTTTTAAACAAGGAGGAGGCTGTTTTGGAGTTAGAGAAGAGAATTGAAGAATCT
TCTGAAACTTGTGAGAAGAAGTCTGATATTGTGCTTCTGCTAAGCCAAAAACAGGCACTT
GAAGAACTGAAACAGTCAGTCCAGCAGCTGAGATGCACTGAAGCAAAGTTTTCAGCACAG
AAGGAATTACTAGAGCAAAAAGTGCAAGAAAATGATGGGAAAGAGCCACCTCCAGTAGTA
AATTATGAAGAAGATGCACGATCAGTTACATCTATGGAAAGAAAGGAGAGGCTATCCAAA
TTTGAATCTATTCGTCATTCAATTGCTGGAATAATTAGGTCTCCAAAATCTGCACTGGGC
TCTTCAGCACTTTCTGATATGATCTCCATCAGTGAGAAGCCTTTGGCAGAACAGGACTGG
TACCATGGTGCAATTCCCAGAATAGAAGCTCAAGAACTGTTAAAAAAACAAGGAGACTTT
TTGGTGCGAGAGAGTCATGGGAAACCTGGTGAATATGTCCTTTCTGTATATTCTGATGGA
CAGAGGAGACATTTTATCATACAATATGTTGATAACATGTATCGATTCGAGGGCACTGGG
TTTTCAAACATTCCTCAACTTATAGATCATCACTATACAACAAAACAGGTCATCACTAAG
AAATCAGGTGTAGTTCTGCTGAATCCTATTCCTAAGGACAAGAAATGGATTCTCAGTCAT
GAAGATGTCATATTGGGAGAATTACTGGGCAAGGGAAATTTTGGTGAAGTATATAAGGGC
ACATTAAAGGATAAAACTTCTGTTGCTGTTAAAACATGTAAAGAAGATCTTCCTCAGGAA
TTGAAAATAAAATTTTTACAAGAAGCCAAAATTCTCAAGCAATATGATCATCCCAATATT
GTCAAACTTATAGGAGTTTGCACACAAAGACAGCCTGTCTACATCATTATGGAACTGGTT
TCAGGAGGTGATTTCCTCACCTTTCTGAGAAGGAAGAAGGATGAACTAAAACTCAAACAG
TTAGTGAAATTTTCATTAGACGCTGCTGCTGGTATGTTGTATCTCGAGAGTAAAAACTGT
ATACACAGGGACCTTGCTGCAAGAAACTGCCTGGTAGGTGAAAATAATGTTCTGAAAATC
AGTGACTTTGGAATGTCTCGTCAAGAGGATGGTGGAGTGTATTCATCTTCTGGCTTAAAG
CAGATTCCCATTAAATGGACAGCACCGGAAGCTCTTAATTATGGGAGATACAGTTCAGAG
AGTGACGTGTGGAGCTTTGGCATCCTTCTCTGGGAGACCTTCAGCTTAGGGGTTTGTCCG
TACCCTGGAATGACAAATCAGCAAGCAAGAGAGCAAGTAGAAAGAGGATACCGGATGTCA
GCTCCCCAGCACTGTCCAGAGGATATTTCCAAAATCATGATGAAGTGTTGGGATTATAAA
CCTGAAAATCGCCCTAAGTTCAGTGAACTTCAGAAAGAGCTCACTATCATCAAGAGAAAA
CTCACATAG
Chromosome Location
5
Locus
5q21.3
External Identifiers
ResourceLink
UniProtKB IDP16591
UniProtKB Entry NameFER_HUMAN
HGNC IDHGNC:3655
General References
  1. Hao QL, Heisterkamp N, Groffen J: Isolation and sequence analysis of a novel human tyrosine kinase gene. Mol Cell Biol. 1989 Apr;9(4):1587-93. [Article]
  2. Makovski A, Yaffe E, Shpungin S, Nir U: Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells. J Biol Chem. 2012 Feb 24;287(9):6100-12. doi: 10.1074/jbc.M111.327106. Epub 2012 Jan 5. [Article]
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  5. Lee ST, Strunk KM, Spritz RA: A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes. Oncogene. 1993 Dec;8(12):3403-10. [Article]
  6. Krolewski JJ, Lee R, Eddy R, Shows TB, Dalla-Favera R: Identification and chromosomal mapping of new human tyrosine kinase genes. Oncogene. 1990 Mar;5(3):277-82. [Article]
  7. Hao QL, Ferris DK, White G, Heisterkamp N, Groffen J: Nuclear and cytoplasmic location of the FER tyrosine kinase. Mol Cell Biol. 1991 Feb;11(2):1180-3. [Article]
  8. Kim L, Wong TW: The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors. Mol Cell Biol. 1995 Aug;15(8):4553-61. [Article]
  9. Kim L, Wong TW: Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the cytoplasmic tyrosine kinase FER. J Biol Chem. 1998 Sep 4;273(36):23542-8. [Article]
  10. Kogata N, Masuda M, Kamioka Y, Yamagishi A, Endo A, Okada M, Mochizuki N: Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells. Mol Biol Cell. 2003 Sep;14(9):3553-64. Epub 2003 Jun 13. [Article]
  11. Miravet S, Piedra J, Castano J, Raurell I, Franci C, Dunach M, Garcia de Herreros A: Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription. Mol Cell Biol. 2003 Oct;23(20):7391-402. [Article]
  12. Tsujita K, Suetsugu S, Sasaki N, Furutani M, Oikawa T, Takenawa T: Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis. J Cell Biol. 2006 Jan 16;172(2):269-79. [Article]
  13. Kierszenbaum AL, Rivkin E, Tres LL: 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. Dev Dyn. 2008 Dec;237(12):3882-91. doi: 10.1002/dvdy.21789. [Article]
  14. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  15. Oh MA, Choi S, Lee MJ, Choi MC, Lee SA, Ko W, Cance WG, Oh ES, Buday L, Kim SH, Lee JW: Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes. Biochim Biophys Acta. 2009 May;1793(5):781-91. doi: 10.1016/j.bbamcr.2009.01.015. Epub 2009 Feb 5. [Article]
  16. Hikri E, Shpungin S, Nir U: Hsp90 and a tyrosine embedded in the Hsp90 recognition loop are required for the Fer tyrosine kinase activity. Cell Signal. 2009 Apr;21(4):588-96. doi: 10.1016/j.cellsig.2008.12.011. Epub 2008 Dec 30. [Article]
  17. Zoubeidi A, Rocha J, Zouanat FZ, Hamel L, Scarlata E, Aprikian AG, Chevalier S: The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth. Mol Cancer Res. 2009 Jan;7(1):142-55. doi: 10.1158/1541-7786.MCR-08-0117. [Article]
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  19. Itoh T, Hasegawa J, Tsujita K, Kanaho Y, Takenawa T: The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration. Sci Signal. 2009 Sep 8;2(87):ra52. doi: 10.1126/scisignal.2000393. [Article]
  20. Voisset E, Lopez S, Chaix A, Georges C, Hanssens K, Prebet T, Dubreuil P, De Sepulveda P: FES kinases are required for oncogenic FLT3 signaling. Leukemia. 2010 Apr;24(4):721-8. doi: 10.1038/leu.2009.301. Epub 2010 Jan 28. [Article]
  21. Guo C, Stark GR: FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-kappaB. Proc Natl Acad Sci U S A. 2011 May 10;108(19):7968-73. doi: 10.1073/pnas.1105369108. Epub 2011 Apr 25. [Article]
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  23. Greer P: Closing in on the biological functions of Fps/Fes and Fer. Nat Rev Mol Cell Biol. 2002 Apr;3(4):278-89. [Article]
  24. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P: Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991 Aug 9;253(5020):665-9. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails