This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Infection with Epstein–Barr virus results in the overexpression of this gene. Multiple alternatively spliced variants, encoding the same protein, have been identified.[6]
Discovery
The feline version of this gene was discovered by Suraiya Rasheed, Murray Gardner, and co-workers.[7]
^Rasheed S, Barbacid M, Aaronson S, Gardner MB (Feb 1982). "Origin and biological properties of a new feline sarcoma virus". Virology. 117 (1): 238–44. doi:10.1016/0042-6822(82)90522-0. PMID 6175084.
^Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I (Aug 1996). "Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981–8. doi:10.1016/S0960-9822(02)00642-5. PMID 8805332. S2CID 162267.
^Finan PM, Soames CJ, Wilson L, Nelson DL, Stewart DM, Truong O, Hsuan JJ, Kellie S (Oct 1996). "Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains" (PDF). The Journal of Biological Chemistry. 271 (42): 26291–5. doi:10.1074/jbc.271.42.26291. PMID 8824280. S2CID 1945958.
^Rivero-Lezcano OM, Marcilla A, Sameshima JH, Robbins KC (Oct 1995). "Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains". Molecular and Cellular Biology. 15 (10): 5725–31. doi:10.1128/MCB.15.10.5725. PMC230823. PMID 7565724.
Further reading
Patel M, Faulkner L, Katz DR, Brickell PM (1991). "The c-fgr proto-oncogene: expression in Epstein-Barr-virus-infected B lymphocytes and in cells of the myelomonocytic and granulocytic lineages". Pathobiology. 59 (4): 289–92. doi:10.1159/000163665. PMID 1652975.
Resh MD (Feb 1994). "Myristylation and palmitylation of Src family members: the fats of the matter". Cell. 76 (3): 411–3. doi:10.1016/0092-8674(94)90104-X. PMID 8313462. S2CID 30267126.
Lowell CA, Berton G (Mar 1999). "Integrin signal transduction in myeloid leukocytes". Journal of Leukocyte Biology. 65 (3): 313–20. doi:10.1002/jlb.65.3.313. PMID 10080533.
Snapper SB, Rosen FS (1999). "The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization". Annual Review of Immunology. 17 (1): 905–29. doi:10.1146/annurev.immunol.17.1.905. PMID 10358777.
Tatosyan AG, Mizenina OA (Jan 2000). "Kinases of the Src family: structure and functions". Biochemistry. Biokhimiia. 65 (1): 49–58. PMID 10702640.
Patel MS, Mankoo BS, Brickell PM (Apr 1992). "A polymorphic microsatellite repeat is located close to the promoter region of the c-fgr proto-oncogene (FGR) at chromosome 1p36.2-p36.1". Human Molecular Genetics. 1 (1): 65. doi:10.1093/hmg/1.1.65-a. PMID 1339476.
Link DC, Gutkind SJ, Robbins KC, Ley TJ (May 1992). "Characterization of the 5' untranslated region of the human c-fgr gene and identification of the major myelomonocytic c-fgr promoter". Oncogene. 7 (5): 877–84. PMID 1373875.
Patel M, Leevers SJ, Brickell PM (Feb 1990). "Structure of the complete human c-fgr proto-oncogene and identification of multiple transcriptional start sites". Oncogene. 5 (2): 201–6. PMID 1690869.
Biondi A, Paganin C, Rossi V, Benvestito S, Perlmutter RM, Mantovani A, Allavena P (Mar 1991). "Expression of lineage-restricted protein tyrosine kinase genes in human natural killer cells". European Journal of Immunology. 21 (3): 843–6. doi:10.1002/eji.1830210348. PMID 1826268. S2CID 26645112.
Gutkind JS, Link DC, Katamine S, Lacal P, Miki T, Ley TJ, Robbins KC (Mar 1991). "A novel c-fgr exon utilized in Epstein-Barr virus-infected B lymphocytes but not in normal monocytes". Molecular and Cellular Biology. 11 (3): 1500–7. doi:10.1128/MCB.11.3.1500. PMC369433. PMID 1847500.
Patel M, Leevers SJ, Brickell PM (Feb 1990). "Regulation of c-fgr proto-oncogene expression in Epstein-Barr virus infected B-cell lines". International Journal of Cancer. 45 (2): 342–6. doi:10.1002/ijc.2910450222. PMID 2154410. S2CID 22888218.
Parker RC, Mardon G, Lebo RV, Varmus HE, Bishop JM (Apr 1985). "Isolation of duplicated human c-src genes located on chromosomes 1 and 20". Molecular and Cellular Biology. 5 (4): 831–8. doi:10.1128/MCB.5.4.831. PMC366788. PMID 2581127.
Brickell PM, Patel M (Dec 1988). "Structure and expression of c-fgr protooncogene mRNA in Epstein-Barr virus converted cell lines". British Journal of Cancer. 58 (6): 704–9. doi:10.1038/bjc.1988.294. PMC2246855. PMID 2852026.
Tronick SR, Popescu NC, Cheah MS, Swan DC, Amsbaugh SC, Lengel CR, DiPaolo JA, Robbins KC (Oct 1985). "Isolation and chromosomal localization of the human fgr protooncogene, a distinct member of the tyrosine kinase gene family". Proceedings of the National Academy of Sciences of the United States of America. 82 (19): 6595–9. Bibcode:1985PNAS...82.6595T. doi:10.1073/pnas.82.19.6595. PMC391256. PMID 2995972.
Cheah MS, Ley TJ, Tronick SR, Robbins KC (1986). "fgr proto-oncogene mRNA induced in B lymphocytes by Epstein-Barr virus infection". Nature. 319 (6050): 238–40. Bibcode:1986Natur.319..238C. doi:10.1038/319238a0. PMID 3003578. S2CID 4323488.
Nishizawa M, Semba K, Yoshida MC, Yamamoto T, Sasaki M, Toyoshima K (Feb 1986). "Structure, expression, and chromosomal location of the human c-fgr gene". Molecular and Cellular Biology. 6 (2): 511–7. doi:10.1128/MCB.6.2.511. PMC367540. PMID 3023853.
Katamine S, Notario V, Rao CD, Miki T, Cheah MS, Tronick SR, Robbins KC (Jan 1988). "Primary structure of the human fgr proto-oncogene product p55c-fgr". Molecular and Cellular Biology. 8 (1): 259–66. doi:10.1128/MCB.8.1.259. PMC363113. PMID 3275868.
Inoue K, Ikawa S, Semba K, Sukegawa J, Yamamoto T, Toyoshima K (1988). "Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene from a human B lymphocyte cell line, IM-9". Oncogene. 1 (3): 301–4. PMID 3330776.
Nishizawa M, Semba K, Yamamoto T, Toyoshima K (Mar 1985). "Human c-f gr gene does not contain coding sequence for actin-like protein". Japanese Journal of Cancer Research. 76 (3): 155–9. PMID 3922831.
gene, gardner, rasheed, feline, sarcoma, viral, oncogene, homolog, also, known, protein, which, humans, encoded, gene, fgridentifiersaliasesfgr, src2, src2, p55c, p58c, proto, oncogene, family, tyrosine, kinaseexternal, idsomim, 164940, 95527, homologene, 3842. Gardner Rasheed feline sarcoma viral v fgr oncogene homolog also known as FGR is a protein which in humans is encoded by the FGR gene 5 6 FGRIdentifiersAliasesFGR SRC2 c fgr c src2 p55 Fgr p55c fgr p58 Fgr p58c fgr FGR proto oncogene Src family tyrosine kinaseExternal IDsOMIM 164940 MGI 95527 HomoloGene 3842 GeneCards FGRGene location Human Chr Chromosome 1 human 1 Band1p35 3Start27 612 064 bp 1 End27 635 185 bp 1 Gene location Mouse Chr Chromosome 4 mouse 2 Band4 D2 3 4 66 11 cMStart132 701 406 bp 2 End132 729 221 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytebloodright lungspleenupper lobe of left lungbone marrow cellscancellous boneappendixlower lobe of lungleft uterine tubeTop expressed inbloodspleenbone marrowoocytesecondary oocytethymusmorularight lung lobesubcutaneous adipose tissuebody of femurMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functiontransferase activity nucleotide binding protein kinase activity immunoglobulin receptor binding kinase activity protein binding Fc gamma receptor I complex binding ATP binding protein kinase binding protein tyrosine kinase activity non membrane spanning protein tyrosine kinase activity phosphotyrosine residue binding signaling receptor bindingCellular componentcytoplasm cytosol cell projection membrane extrinsic component of cytoplasmic side of plasma membrane mitochondrial intermembrane space ruffle membrane mitochondrion actin cytoskeleton mitochondrial inner membrane extracellular exosome cytoskeleton extracellular region plasma membrane aggresome secretory granule lumenBiological processcell differentiation regulation of innate immune response Fc gamma receptor signaling pathway involved in phagocytosis phosphorylation transmembrane receptor protein tyrosine kinase signaling pathway immune system process positive regulation of cell migration response to virus positive regulation of mast cell degranulation immune response regulating cell surface receptor signaling pathway positive regulation of phosphatidylinositol 3 kinase activity protein phosphorylation regulation of cell population proliferation regulation of cell shape peptidyl tyrosine autophosphorylation integrin mediated signaling pathway protein autophosphorylation positive regulation of phosphatidylinositol 3 kinase signaling peptidyl tyrosine phosphorylation regulation of protein kinase activity regulation of phagocytosis defense response to Gram positive bacterium cell migration innate immune response neutrophil degranulation bone mineralization skeletal system morphogenesisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez226814191EnsemblENSG00000000938ENSMUSG00000028874UniProtP09769P14234RefSeq mRNA NM 001042729NM 001042747NM 005248NM 010208RefSeq protein NP 001036194NP 001036212NP 005239NP 034338Location UCSC Chr 1 27 61 27 64 MbChr 4 132 7 132 73 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Discovery 3 Interactions 4 References 5 Further readingFunction EditThis gene is a member of the Src family of protein tyrosine kinases PTKs The encoded protein contains N terminal sites for myristoylation and palmitoylation a PTK domain and SH2 and SH3 domains which are involved in mediating protein protein interactions with phosphotyrosine containing and proline rich motifs respectively The protein localizes to plasma membrane ruffles and functions as a negative regulator of cell migration and adhesion triggered by the beta 2 integrin signal transduction pathway Infection with Epstein Barr virus results in the overexpression of this gene Multiple alternatively spliced variants encoding the same protein have been identified 6 Discovery EditThe feline version of this gene was discovered by Suraiya Rasheed Murray Gardner and co workers 7 Interactions EditFGR gene has been shown to interact with Wiskott Aldrich syndrome protein 8 9 10 References Edit a b c GRCh38 Ensembl release 89 ENSG00000000938 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000028874 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Tronick SR Popescu NC Cheah MS Swan DC Amsbaugh SC Lengel CR DiPaolo JA Robbins KC Oct 1985 Isolation and chromosomal localization of the human fgr protooncogene a distinct member of the tyrosine kinase gene family Proc Natl Acad Sci U S A 82 19 6595 9 Bibcode 1985PNAS 82 6595T doi 10 1073 pnas 82 19 6595 PMC 391256 PMID 2995972 a b Entrez Gene FGR Gardner Rasheed feline sarcoma viral v fgr oncogene homolog Rasheed S Barbacid M Aaronson S Gardner MB Feb 1982 Origin and biological properties of a new feline sarcoma virus Virology 117 1 238 44 doi 10 1016 0042 6822 82 90522 0 PMID 6175084 Banin S Truong O Katz DR Waterfield MD Brickell PM Gout I Aug 1996 Wiskott Aldrich syndrome protein WASp is a binding partner for c Src family protein tyrosine kinases Current Biology 6 8 981 8 doi 10 1016 S0960 9822 02 00642 5 PMID 8805332 S2CID 162267 Finan PM Soames CJ Wilson L Nelson DL Stewart DM Truong O Hsuan JJ Kellie S Oct 1996 Identification of regions of the Wiskott Aldrich syndrome protein responsible for association with selected Src homology 3 domains PDF The Journal of Biological Chemistry 271 42 26291 5 doi 10 1074 jbc 271 42 26291 PMID 8824280 S2CID 1945958 Rivero Lezcano OM Marcilla A Sameshima JH Robbins KC Oct 1995 Wiskott Aldrich syndrome protein physically associates with Nck through Src homology 3 domains Molecular and Cellular Biology 15 10 5725 31 doi 10 1128 MCB 15 10 5725 PMC 230823 PMID 7565724 Further reading EditPatel M Faulkner L Katz DR Brickell PM 1991 The c fgr proto oncogene expression in Epstein Barr virus infected B lymphocytes and in cells of the myelomonocytic and granulocytic lineages Pathobiology 59 4 289 92 doi 10 1159 000163665 PMID 1652975 Resh MD Feb 1994 Myristylation and palmitylation of Src family members the fats of the matter Cell 76 3 411 3 doi 10 1016 0092 8674 94 90104 X PMID 8313462 S2CID 30267126 Lowell CA Berton G Mar 1999 Integrin signal transduction in myeloid leukocytes Journal of Leukocyte Biology 65 3 313 20 doi 10 1002 jlb 65 3 313 PMID 10080533 Snapper SB Rosen FS 1999 The Wiskott Aldrich syndrome protein WASP roles in signaling and cytoskeletal organization Annual Review of Immunology 17 1 905 29 doi 10 1146 annurev immunol 17 1 905 PMID 10358777 Tatosyan AG Mizenina OA Jan 2000 Kinases of the Src family structure and functions Biochemistry Biokhimiia 65 1 49 58 PMID 10702640 Patel MS Mankoo BS Brickell PM Apr 1992 A polymorphic microsatellite repeat is located close to the promoter region of the c fgr proto oncogene FGR at chromosome 1p36 2 p36 1 Human Molecular Genetics 1 1 65 doi 10 1093 hmg 1 1 65 a PMID 1339476 Link DC Gutkind SJ Robbins KC Ley TJ May 1992 Characterization of the 5 untranslated region of the human c fgr gene and identification of the major myelomonocytic c fgr promoter Oncogene 7 5 877 84 PMID 1373875 Patel M Leevers SJ Brickell PM Feb 1990 Structure of the complete human c fgr proto oncogene and identification of multiple transcriptional start sites Oncogene 5 2 201 6 PMID 1690869 Biondi A Paganin C Rossi V Benvestito S Perlmutter RM Mantovani A Allavena P Mar 1991 Expression of lineage restricted protein tyrosine kinase genes in human natural killer cells European Journal of Immunology 21 3 843 6 doi 10 1002 eji 1830210348 PMID 1826268 S2CID 26645112 Gutkind JS Link DC Katamine S Lacal P Miki T Ley TJ Robbins KC Mar 1991 A novel c fgr exon utilized in Epstein Barr virus infected B lymphocytes but not in normal monocytes Molecular and Cellular Biology 11 3 1500 7 doi 10 1128 MCB 11 3 1500 PMC 369433 PMID 1847500 Patel M Leevers SJ Brickell PM Feb 1990 Regulation of c fgr proto oncogene expression in Epstein Barr virus infected B cell lines International Journal of Cancer 45 2 342 6 doi 10 1002 ijc 2910450222 PMID 2154410 S2CID 22888218 Parker RC Mardon G Lebo RV Varmus HE Bishop JM Apr 1985 Isolation of duplicated human c src genes located on chromosomes 1 and 20 Molecular and Cellular Biology 5 4 831 8 doi 10 1128 MCB 5 4 831 PMC 366788 PMID 2581127 Brickell PM Patel M Dec 1988 Structure and expression of c fgr protooncogene mRNA in Epstein Barr virus converted cell lines British Journal of Cancer 58 6 704 9 doi 10 1038 bjc 1988 294 PMC 2246855 PMID 2852026 Tronick SR Popescu NC Cheah MS Swan DC Amsbaugh SC Lengel CR DiPaolo JA Robbins KC Oct 1985 Isolation and chromosomal localization of the human fgr protooncogene a distinct member of the tyrosine kinase gene family Proceedings of the National Academy of Sciences of the United States of America 82 19 6595 9 Bibcode 1985PNAS 82 6595T doi 10 1073 pnas 82 19 6595 PMC 391256 PMID 2995972 Cheah MS Ley TJ Tronick SR Robbins KC 1986 fgr proto oncogene mRNA induced in B lymphocytes by Epstein Barr virus infection Nature 319 6050 238 40 Bibcode 1986Natur 319 238C doi 10 1038 319238a0 PMID 3003578 S2CID 4323488 Nishizawa M Semba K Yoshida MC Yamamoto T Sasaki M Toyoshima K Feb 1986 Structure expression and chromosomal location of the human c fgr gene Molecular and Cellular Biology 6 2 511 7 doi 10 1128 MCB 6 2 511 PMC 367540 PMID 3023853 Katamine S Notario V Rao CD Miki T Cheah MS Tronick SR Robbins KC Jan 1988 Primary structure of the human fgr proto oncogene product p55c fgr Molecular and Cellular Biology 8 1 259 66 doi 10 1128 MCB 8 1 259 PMC 363113 PMID 3275868 Inoue K Ikawa S Semba K Sukegawa J Yamamoto T Toyoshima K 1988 Isolation and sequencing of cDNA clones homologous to the v fgr oncogene from a human B lymphocyte cell line IM 9 Oncogene 1 3 301 4 PMID 3330776 Nishizawa M Semba K Yamamoto T Toyoshima K Mar 1985 Human c f gr gene does not contain coding sequence for actin like protein Japanese Journal of Cancer Research 76 3 155 9 PMID 3922831 Portal Biology This article on a 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