Tyrosine-protein kinase Fgr

Details

Name
Tyrosine-protein kinase Fgr
Synonyms
  • 2.7.10.2
  • Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog
  • p55-Fgr
  • p58-Fgr
  • p58c-Fgr
  • Proto-oncogene c-Fgr
  • SRC2
Gene Name
FGR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021448|Tyrosine-protein kinase Fgr
MGCVFCKKLEPVATAKEDAGLEGDFRSYGAADHYGPDPTKARPASSFAHIPNYSNFSSQA
INPGFLDSGTIRGVSGIGVTLFIALYDYEARTEDDLTFTKGEKFHILNNTEGDWWEARSL
SSGKTGCIPSNYVAPVDSIQAEEWYFGKIGRKDAERQLLSPGNPQGAFLIRESETTKGAY
SLSIRDWDQTRGDHVKHYKIRKLDMGGYYITTRVQFNSVQELVQHYMEVNDGLCNLLIAP
CTIMKPQTLGLAKDAWEISRSSITLERRLGTGCFGDVWLGTWNGSTKVAVKTLKPGTMSP
KAFLEEAQVMKLLRHDKLVQLYAVVSEEPIYIVTEFMCHGSLLDFLKNPEGQDLRLPQLV
DMAAQVAEGMAYMERMNYIHRDLRAANILVGERLACKIADFGLARLIKDDEYNPCQGSKF
PIKWTAPEAALFGRFTIKSDVWSFGILLTELITKGRIPYPGMNKREVLEQVEQGYHMPCP
PGCPASLYEAMEQTWRLDPEERPTFEYLQSFLEDYFTSAEPQYQPGDQT
Number of residues
529
Molecular Weight
59478.11
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / Fc-gamma receptor I complex binding / immunoglobulin receptor binding / non-membrane spanning protein tyrosine kinase activity / phosphotyrosine binding / protein kinase binding / protein tyrosine kinase activity
Processes
blood coagulation / cell differentiation / cellular response to peptide hormone stimulus / defense response to Gram-positive bacterium / Fc-gamma receptor signaling pathway involved in phagocytosis / immune response-regulating cell surface receptor signaling pathway / innate immune response / integrin-mediated signaling pathway / peptidyl-tyrosine autophosphorylation / peptidyl-tyrosine phosphorylation / positive regulation of cell migration / positive regulation of cytokine secretion / positive regulation of mast cell degranulation / positive regulation of phosphatidylinositol 3-kinase activity / positive regulation of phosphatidylinositol 3-kinase signaling / protein autophosphorylation / protein phosphorylation / regulation of cell proliferation / regulation of cell shape / regulation of innate immune response / regulation of phagocytosis / regulation of protein kinase activity / response to virus / transmembrane receptor protein tyrosine kinase signaling pathway
Components
actin cytoskeleton / cytosol / extracellular exosome / extrinsic component of cytoplasmic side of plasma membrane / mitochondrial inner membrane / mitochondrial intermembrane space / plasma membrane / ruffle membrane
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021449|Tyrosine-protein kinase Fgr (FGR)
ATGGGCTGTGTGTTCTGCAAGAAATTGGAGCCGGTGGCCACGGCCAAGGAGGATGCTGGC
CTGGAAGGGGACTTCAGAAGCTACGGGGCAGCAGACCACTATGGGCCTGACCCCACTAAG
GCCCGGCCTGCATCCTCATTTGCCCACATCCCCAACTACAGCAACTTCTCCTCTCAGGCC
ATCAACCCTGGCTTCCTTGATAGTGGCACCATCAGGGGTGTGTCAGGGATTGGGGTGACC
CTGTTCATTGCCCTGTATGACTATGAGGCTCGAACTGAGGATGACCTCACCTTCACCAAG
GGCGAGAAGTTCCACATCCTGAACAATACTGAAGGTGACTGGTGGGAGGCTCGGTCTCTC
AGCTCCGGAAAAACTGGCTGCATTCCCAGCAACTACGTGGCCCCTGTTGACTCAATCCAA
GCTGAAGAGTGGTACTTTGGAAAGATTGGGAGAAAGGATGCAGAGAGGCAGCTGCTTTCA
CCAGGCAACCCCCAGGGGGCCTTTCTCATTCGGGAAAGCGAGACCACCAAAGGTGCCTAC
TCCCTGTCCATCCGGGACTGGGATCAGACCAGAGGCGATCATGTGAAGCATTACAAGATC
CGCAAACTGGACATGGGCGGCTACTACATCACCACACGGGTTCAGTTCAACTCGGTGCAG
GAGCTGGTGCAGCACTACATGGAGGTGAATGACGGGCTGTGCAACCTGCTCATCGCGCCC
TGCACCATCATGAAGCCGCAGACGCTGGGCCTGGCCAAGGACGCCTGGGAGATCAGCCGC
AGCTCCATCACGCTGGAGCGCCGGCTGGGCACCGGCTGCTTCGGGGATGTGTGGCTGGGC
ACGTGGAACGGCAGCACTAAGGTGGCGGTGAAGACGCTGAAGCCGGGCACCATGTCCCCG
AAGGCCTTCCTGGAGGAGGCGCAGGTCATGAAGCTGCTGCGGCACGACAAGCTGGTGCAG
CTGTACGCCGTGGTGTCGGAGGAGCCCATCTACATCGTGACCGAGTTCATGTGTCACGGC
AGCTTGCTGGATTTTCTCAAGAACCCAGAGGGCCAGGATTTGAGGCTGCCCCAATTGGTG
GACATGGCAGCCCAGGTAGCTGAGGGCATGGCCTACATGGAACGCATGAACTACATTCAC
CGCGACCTGAGGGCAGCCAACATCCTGGTTGGGGAGCGGCTGGCGTGCAAGATCGCAGAC
TTTGGCTTGGCGCGTCTCATCAAGGACGATGAGTACAACCCCTGCCAAGGTTCCAAGTTC
CCCATCAAGTGGACAGCCCCAGAAGCTGCCCTCTTTGGCAGATTCACCATCAAGTCAGAC
GTGTGGTCCTTTGGGATCCTGCTCACTGAGCTCATCACCAAGGGCCGAATCCCCTACCCA
GGCATGAATAAACGGGAAGTGTTGGAACAGGTGGAGCAGGGCTACCACATGCCGTGCCCT
CCAGGCTGCCCAGCATCCCTGTACGAGGCCATGGAACAGACCTGGCGTCTGGACCCGGAG
GAGAGGCCTACCTTCGAGTACCTGCAGTCCTTCCTGGAGGACTACTTCACCTCCGCTGAA
CCACAGTACCAGCCCGGGGATCAGACATAG
Chromosome Location
1
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP09769
UniProtKB Entry NameFGR_HUMAN
HGNC IDHGNC:3697
General References
  1. Katamine S, Notario V, Rao CD, Miki T, Cheah MS, Tronick SR, Robbins KC: Primary structure of the human fgr proto-oncogene product p55c-fgr. Mol Cell Biol. 1988 Jan;8(1):259-66. [Article]
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  4. Brickell PM, Patel M: Structure and expression of c-fgr protooncogene mRNA in Epstein-Barr virus converted cell lines. Br J Cancer. 1988 Dec;58(6):704-9. [Article]
  5. Inoue K, Ikawa S, Semba K, Sukegawa J, Yamamoto T, Toyoshima K: Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9. Oncogene. 1987;1(3):301-4. [Article]
  6. Patel M, Leevers SJ, Brickell PM: Structure of the complete human c-fgr proto-oncogene and identification of multiple transcriptional start sites. Oncogene. 1990 Feb;5(2):201-6. [Article]
  7. Nishizawa M, Semba K, Yoshida MC, Yamamoto T, Sasaki M, Toyoshima K: Structure, expression, and chromosomal location of the human c-fgr gene. Mol Cell Biol. 1986 Feb;6(2):511-7. [Article]
  8. Inoue K, Yamamoto T, Toyoshima K: Specific expression of human c-fgr in natural immunity effector cells. Mol Cell Biol. 1990 Apr;10(4):1789-92. [Article]
  9. Sartor O, Moriuchi R, Sameshima JH, Severino M, Gutkind JS, Robbins KC: Diverse biologic properties imparted by the c-fgr proto-oncogene. J Biol Chem. 1992 Feb 15;267(5):3460-5. [Article]
  10. Hamada F, Aoki M, Akiyama T, Toyoshima K: Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6305-9. [Article]
  11. Berton G, Fumagalli L, Laudanna C, Sorio C: Beta 2 integrin-dependent protein tyrosine phosphorylation and activation of the FGR protein tyrosine kinase in human neutrophils. J Cell Biol. 1994 Aug;126(4):1111-21. [Article]
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  15. Melander F, Andersson T, Dib K: Fgr but not Syk tyrosine kinase is a target for beta 2 integrin-induced c-Cbl-mediated ubiquitination in adherent human neutrophils. Biochem J. 2003 Mar 1;370(Pt 2):687-94. [Article]
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  17. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01254Dasatinibapproved, investigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15035Zanubrutinibapproved, investigationalunknowninhibitorDetails
DB06616BosutinibapprovedyesinhibitorDetails