Tyrosine-protein kinase Fgr
Details
- Name
- Tyrosine-protein kinase Fgr
- Kind
- protein
- 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
- UniProtKB Entry
- P09769Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- 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
- Functionsphosphotyrosine residue binding / signaling receptor bindingProcessesbone mineralization / cell surface receptor protein tyrosine kinase signaling pathway / myoblast proliferation / negative regulation of inflammatory response to antigenic stimulus / negative regulation of natural killer cell activation / positive regulation of cytokine production / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / skeletal system morphogenesisComponentsaggresome / extracellular region / secretory granule lumen
- General 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 a 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 a 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. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity)
- Specific Function
- ATP binding
- Pfam Domain Function
- Signal Regions
- Not Available
- 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
- 1p35.3
- External Identifiers
Resource Link UniProtKB ID P09769 UniProtKB Entry Name FGR_HUMAN GeneCard ID FGR HGNC ID HGNC:3697 PDB ID(s) 7JT9, 7UY0, 7UY3 KEGG ID hsa:2268 IUPHAR/Guide To Pharmacology ID 2024 NCBI Gene ID 2268 - General References
- 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]
- Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Yan SR, Fumagalli L, Berton G: Activation of SRC family kinases in human neutrophils. Evidence that p58C-FGR and p53/56LYN redistributed to a Triton X-100-insoluble cytoskeletal fraction, also enriched in the caveolar protein caveolin, display an enhanced kinase activity. FEBS Lett. 1996 Feb 12;380(1-2):198-203. [Article]
- Axelsson L, Hellberg C, Melander F, Smith D, Zheng L, Andersson T: Clustering of beta(2)-integrins on human neutrophils activates dual signaling pathways to PtdIns 3-kinase. Exp Cell Res. 2000 Apr 10;256(1):257-63. [Article]
- Sergeant S, Waite KA, Heravi J, McPhail LC: Phosphatidic acid regulates tyrosine phosphorylating activity in human neutrophils: enhancement of Fgr activity. J Biol Chem. 2001 Feb 16;276(7):4737-46. Epub 2000 Nov 14. [Article]
- 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]
- Zuccato E, Blott EJ, Holt O, Sigismund S, Shaw M, Bossi G, Griffiths GM: Sorting of Fas ligand to secretory lysosomes is regulated by mono-ubiquitylation and phosphorylation. J Cell Sci. 2007 Jan 1;120(Pt 1):191-9. Epub 2006 Dec 12. [Article]
- 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]
- Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, 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 DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Dasatinib approved, investigational unknown target inhibitor Details Fostamatinib approved, investigational unknown target inhibitor Details Zanubrutinib approved, investigational unknown target inhibitor Details Bosutinib approved yes target inhibitor Details