ID FGR_HUMAN Reviewed; 529 AA. AC P09769; D3DPL7; Q9UIQ3; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1990, sequence version 2. DT 27-MAR-2024, entry version 236. DE RecName: Full=Tyrosine-protein kinase Fgr; DE EC=2.7.10.2; DE AltName: Full=Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog; DE AltName: Full=Proto-oncogene c-Fgr; DE AltName: Full=p55-Fgr; DE AltName: Full=p58-Fgr; DE AltName: Full=p58c-Fgr; GN Name=FGR; Synonyms=SRC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3275868; DOI=10.1128/mcb.8.1.259-266.1988; RA Katamine S., Notario V., Rao C.D., Miki T., Cheah M.S.C., Tronick S.R., RA Robbins K.C.; RT "Primary structure of the human fgr proto-oncogene product p55c-fgr."; RL Mol. Cell. Biol. 8:259-266(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-177 AND 524-529. RX PubMed=2852026; DOI=10.1038/bjc.1988.294; RA Brickell P.M., Patel M.; RT "Structure and expression of c-fgr protooncogene mRNA in Epstein-Barr virus RT converted cell lines."; RL Br. J. Cancer 58:704-709(1988). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-143. RX PubMed=3330776; RA Inoue K., Ikawa S., Semba K., Sukegawa J., Yamamoto T., Toyoshima K.; RT "Isolation and sequencing of cDNA clones homologous to the v-fgr oncogene RT from a human B lymphocyte cell line, IM-9."; RL Oncogene 1:301-304(1987). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-142. RX PubMed=1690869; RA Patel M., Leevers S.J., Brickell P.M.; RT "Structure of the complete human c-fgr proto-oncogene and identification of RT multiple transcriptional start sites."; RL Oncogene 5:201-206(1990). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 111-416. RX PubMed=3023853; DOI=10.1128/mcb.6.2.511-517.1986; RA Nishizawa M., Semba K., Yoshida M.C., Yamamoto T., Sasaki M., Toyoshima K.; RT "Structure, expression, and chromosomal location of the human c-fgr gene."; RL Mol. Cell. Biol. 6:511-517(1986). RN [9] RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY. RX PubMed=2181286; DOI=10.1128/mcb.10.4.1789-1792.1990; RA Inoue K., Yamamoto T., Toyoshima K.; RT "Specific expression of human c-fgr in natural immunity effector cells."; RL Mol. Cell. Biol. 10:1789-1792(1990). RN [10] RP FUNCTION AS PROTO-ONCOGENE, ROLE IN DISEASE, CATALYTIC ACTIVITY, AND RP MUTAGENESIS OF TYR-523. RX PubMed=1737799; DOI=10.1016/s0021-9258(19)50753-0; RA Sartor O., Moriuchi R., Sameshima J.H., Severino M., Gutkind J.S., RA Robbins K.C.; RT "Diverse biologic properties imparted by the c-fgr proto-oncogene."; RL J. Biol. Chem. 267:3460-3465(1992). RN [11] RP INTERACTION WITH FCGR2A AND/OR FCGR2B, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY. RX PubMed=8327512; DOI=10.1073/pnas.90.13.6305; RA Hamada F., Aoki M., Akiyama T., Toyoshima K.; RT "Association of immunoglobulin G Fc receptor II with Src-like protein- RT tyrosine kinase Fgr in neutrophils."; RL Proc. Natl. Acad. Sci. U.S.A. 90:6305-6309(1993). RN [12] RP PHOSPHORYLATION, AND FUNCTION IN INTEGRIN SIGNALING. RX PubMed=7519620; DOI=10.1083/jcb.126.4.1111; RA Berton G., Fumagalli L., Laudanna C., Sorio C.; RT "Beta 2 integrin-dependent protein tyrosine phosphorylation and activation RT of the FGR protein tyrosine kinase in human neutrophils."; RL J. Cell Biol. 126:1111-1121(1994). RN [13] RP SUBCELLULAR LOCATION AT THE CYTOSKELETON, AND ACTIVITY REGULATION. RX PubMed=8603737; DOI=10.1016/0014-5793(96)00029-4; RA Yan S.R., Fumagalli L., Berton G.; RT "Activation of SRC family kinases in human neutrophils. Evidence that p58C- RT FGR and p53/56LYN redistributed to a Triton X-100-insoluble cytoskeletal RT fraction, also enriched in the caveolar protein caveolin, display an RT enhanced kinase activity."; RL FEBS Lett. 380:198-203(1996). RN [14] RP FUNCTION IN ACTIVATION OF PIK3R1, PHOSPHORYLATION, AND INTERACTION WITH RP ITGB2 AND PIK3R1. RX PubMed=10739672; DOI=10.1006/excr.2000.4816; RA Axelsson L., Hellberg C., Melander F., Smith D., Zheng L., Andersson T.; RT "Clustering of beta(2)-integrins on human neutrophils activates dual RT signaling pathways to PtdIns 3-kinase."; RL Exp. Cell Res. 256:257-263(2000). RN [15] RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11078731; DOI=10.1074/jbc.m006571200; RA Sergeant S., Waite K.A., Heravi J., McPhail L.C.; RT "Phosphatidic acid regulates tyrosine phosphorylating activity in human RT neutrophils: enhancement of Fgr activity."; RL J. Biol. Chem. 276:4737-4746(2001). RN [16] RP UBIQUITINATION, AND INTERACTION WITH CBL. RX PubMed=12435267; DOI=10.1042/bj20021201; RA Melander F., Andersson T., Dib K.; RT "Fgr but not Syk tyrosine kinase is a target for beta 2 integrin-induced c- RT Cbl-mediated ubiquitination in adherent human neutrophils."; RL Biochem. J. 370:687-694(2003). RN [17] RP FUNCTION IN PHOSPHORYLATION OF FASLG, AND INTERACTION WITH FASLG. RX PubMed=17164290; DOI=10.1242/jcs.03315; RA Zuccato E., Blott E.J., Holt O., Sigismund S., Shaw M., Bossi G., RA Griffiths G.M.; RT "Sorting of Fas ligand to secretory lysosomes is regulated by mono- RT ubiquitylation and phosphorylation."; RL J. Cell Sci. 120:191-199(2007). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-34; TYR-412 AND TYR-523, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [19] RP VARIANTS [LARGE SCALE ANALYSIS] ILE-110 AND ARG-130. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that transmits signals CC from cell surface receptors devoid of kinase activity and contributes CC to the regulation of immune responses, including neutrophil, monocyte, CC macrophage and mast cell functions, cytoskeleton remodeling in response CC to extracellular stimuli, phagocytosis, cell adhesion and migration. CC Promotes mast cell degranulation, release of inflammatory cytokines and CC IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc CC region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. CC Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton CC reorganization, cell spreading and adhesion. Depending on the context, CC activates or inhibits cellular responses. Functions as a negative CC regulator of ITGB2 signaling, phagocytosis and SYK activity in CC monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell CC spreading and adhesion in neutrophils and macrophages. Functions as a CC positive regulator of cell migration and regulates cytoskeleton CC reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and CC promotes SYK-dependent activation of AKT1 and MAP kinase signaling. CC Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 CC activation and the production of the signaling molecules CC lysophosphatidic acid and diacylglycerol. Promotes activation of CC PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination CC and subsequent internalization. Phosphorylates ABL1. Promotes CC phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. CC Phosphorylates HCLS1 that has already been phosphorylated by SYK, but CC not unphosphorylated HCLS1. Together with CLNK, it acts as a negative CC regulator of natural killer cell-activating receptors and inhibits CC interferon-gamma production (By similarity). CC {ECO:0000250|UniProtKB:P14234, ECO:0000269|PubMed:10739672, CC ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, CC ECO:0000269|PubMed:7519620}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:2181286, CC ECO:0000269|PubMed:8327512}; CC -!- ACTIVITY REGULATION: Activated by autophosphorylation. Prior CC phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation CC at Tyr-412. Activated by phorbol myristate acetate, phosphatidic acid CC and poly-Lys. Binding (via SH2 domain) of HCLS1 that is already CC phosphorylated by SYK strongly increases kinase activity. CC {ECO:0000269|PubMed:11078731, ECO:0000269|PubMed:8327512, CC ECO:0000269|PubMed:8603737}. CC -!- SUBUNIT: Interacts with ITGB1, ITGB2, MS4A2/FCER1B, FCER1G, FCGR2A CC and/or FCGR2B. Interacts (via SH2 domain) with SYK (tyrosine CC phosphorylated). Interacts (via SH2 domain) with FLT3 (tyrosine CC phosphorylated). Interacts with PTK2/FAK1. Interacts (via SH2 domain) CC with HCLS1 (tyrosine phosphorylated by SYK). Interacts with SIRPA and CC PTPNS1. Interacts (not phosphorylated on tyrosine residues) with CBL; CC FGR tyrosine phosphorylation promotes dissociation. Interacts with CC PIK3R1 and FASLG (By similarity). Interacts with CLNK (By similarity). CC {ECO:0000250, ECO:0000250|UniProtKB:P14234}. CC -!- INTERACTION: CC P09769; P09917: ALOX5; NbExp=2; IntAct=EBI-1383732, EBI-79934; CC P09769; P10275: AR; NbExp=3; IntAct=EBI-1383732, EBI-608057; CC P09769; P00533: EGFR; NbExp=3; IntAct=EBI-1383732, EBI-297353; CC P09769; P04626: ERBB2; NbExp=3; IntAct=EBI-1383732, EBI-641062; CC P09769; P08238: HSP90AB1; NbExp=4; IntAct=EBI-1383732, EBI-352572; CC P09769; P10721: KIT; NbExp=2; IntAct=EBI-1383732, EBI-1379503; CC P09769; P08581: MET; NbExp=2; IntAct=EBI-1383732, EBI-1039152; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cell membrane; CC Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle CC membrane. Cytoplasm, cytosol. Cytoplasm, cytoskeleton. Mitochondrion CC inner membrane {ECO:0000250}. Mitochondrion intermembrane space CC {ECO:0000250}. Note=Detected in mitochondrial intermembrane space and CC at inner membranes (By similarity). Colocalizes with actin fibers at CC membrane ruffles. Detected at plasma membrane lipid rafts. CC {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Detected in neutrophils, monocytes and natural CC killer cells (at protein level). Detected in monocytes and large CC lymphocytes. {ECO:0000269|PubMed:11078731, ECO:0000269|PubMed:2181286, CC ECO:0000269|PubMed:8327512}. CC -!- PTM: Ubiquitinated. Becomes ubiquitinated in response to ITGB2 CC signaling; this does not lead to degradation. CC {ECO:0000269|PubMed:12435267}. CC -!- PTM: Phosphorylated. Autophosphorylated on tyrosine residues. Becomes CC phosphorylated in response to FCGR2A and/or FCGR2B engagement, cell CC adhesion and signaling by ITGB2. Prior phosphorylation at Tyr-523 by CC SRC inhibits ulterior autophosphorylation at Tyr-412. CC {ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:7519620}. CC -!- DISEASE: Note=Mutations that cause aberrant kinase activation can CC confer oncogene activity and promote aberrant cell proliferation. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M19722; AAA52451.1; -; mRNA. DR EMBL; AL031729; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07748.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07749.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07750.1; -; Genomic_DNA. DR EMBL; BC064382; AAH64382.1; -; mRNA. DR EMBL; X52207; CAA36457.2; -; Genomic_DNA. DR EMBL; X52208; CAA36457.2; JOINED; Genomic_DNA. DR EMBL; M12724; AAA52762.1; -; Genomic_DNA. DR EMBL; M12719; AAA52762.1; JOINED; Genomic_DNA. DR EMBL; M12720; AAA52762.1; JOINED; Genomic_DNA. DR EMBL; M12721; AAA52762.1; JOINED; Genomic_DNA. DR EMBL; M12722; AAA52762.1; JOINED; Genomic_DNA. DR EMBL; M12723; AAA52762.1; JOINED; Genomic_DNA. DR CCDS; CCDS305.1; -. DR PIR; A27676; TVHUFR. DR RefSeq; NP_001036194.1; NM_001042729.1. DR RefSeq; NP_001036212.1; NM_001042747.1. DR RefSeq; NP_005239.1; NM_005248.2. DR RefSeq; XP_006710515.1; XM_006710452.2. DR RefSeq; XP_011539312.1; XM_011541010.1. DR PDB; 7JT9; X-ray; 1.93 A; A=77-138. DR PDB; 7UY0; X-ray; 2.55 A; A/B=80-527. DR PDB; 7UY3; X-ray; 2.99 A; A=80-527. DR PDBsum; 7JT9; -. DR PDBsum; 7UY0; -. DR PDBsum; 7UY3; -. DR AlphaFoldDB; P09769; -. DR SMR; P09769; -. DR BioGRID; 108559; 86. DR DIP; DIP-1049N; -. DR ELM; P09769; -. DR IntAct; P09769; 66. DR MINT; P09769; -. DR STRING; 9606.ENSP00000363117; -. DR BindingDB; P09769; -. DR ChEMBL; CHEMBL4454; -. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB15035; Zanubrutinib. DR DrugCentral; P09769; -. DR GuidetoPHARMACOLOGY; 2024; -. DR GlyGen; P09769; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P09769; -. DR PhosphoSitePlus; P09769; -. DR SwissPalm; P09769; -. DR BioMuta; FGR; -. DR DMDM; 125358; -. DR CPTAC; CPTAC-1786; -. DR CPTAC; CPTAC-3064; -. DR EPD; P09769; -. DR jPOST; P09769; -. DR MassIVE; P09769; -. DR MaxQB; P09769; -. DR PaxDb; 9606-ENSP00000363117; -. DR PeptideAtlas; P09769; -. DR ProteomicsDB; 52268; -. DR Antibodypedia; 711; 614 antibodies from 39 providers. DR DNASU; 2268; -. DR Ensembl; ENST00000374003.7; ENSP00000363115.3; ENSG00000000938.13. DR Ensembl; ENST00000374004.5; ENSP00000363116.1; ENSG00000000938.13. DR Ensembl; ENST00000374005.8; ENSP00000363117.3; ENSG00000000938.13. DR Ensembl; ENST00000399173.5; ENSP00000382126.1; ENSG00000000938.13. DR GeneID; 2268; -. DR KEGG; hsa:2268; -. DR MANE-Select; ENST00000374005.8; ENSP00000363117.3; NM_005248.3; NP_005239.1. DR UCSC; uc001boj.4; human. DR AGR; HGNC:3697; -. DR CTD; 2268; -. DR DisGeNET; 2268; -. DR GeneCards; FGR; -. DR HGNC; HGNC:3697; FGR. DR HPA; ENSG00000000938; Group enriched (bone marrow, lung, lymphoid tissue). DR MIM; 164940; gene. DR neXtProt; NX_P09769; -. DR OpenTargets; ENSG00000000938; -. DR PharmGKB; PA28135; -. DR VEuPathDB; HostDB:ENSG00000000938; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000157554; -. DR HOGENOM; CLU_000288_7_2_1; -. DR InParanoid; P09769; -. DR OMA; VDWWEAR; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P09769; -. DR TreeFam; TF351634; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; P09769; -. DR Reactome; R-HSA-2029481; FCGR activation. DR Reactome; R-HSA-432142; Platelet sensitization by LDL. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis. DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis. DR SignaLink; P09769; -. DR SIGNOR; P09769; -. DR BioGRID-ORCS; 2268; 13 hits in 1177 CRISPR screens. DR ChiTaRS; FGR; human. DR GeneWiki; FGR_(gene); -. DR GenomeRNAi; 2268; -. DR Pharos; P09769; Tchem. DR PRO; PR:P09769; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P09769; Protein. DR Bgee; ENSG00000000938; Expressed in granulocyte and 121 other cell types or tissues. DR ExpressionAtlas; P09769; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl. DR GO; GO:0016235; C:aggresome; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0034988; F:Fc-gamma receptor I complex binding; IDA:UniProtKB. DR GO; GO:0034987; F:immunoglobulin receptor binding; ISS:UniProtKB. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central. DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0002768; P:immune response-regulating cell surface receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0051450; P:myoblast proliferation; IEA:Ensembl. DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome. DR GO; GO:0032815; P:negative regulation of natural killer cell activation; IEA:Ensembl. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB. DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; ISS:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB. DR GO; GO:0045088; P:regulation of innate immune response; ISS:UniProtKB. DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB. DR GO; GO:0045859; P:regulation of protein kinase activity; ISS:UniProtKB. DR GO; GO:0009615; P:response to virus; TAS:ProtInc. DR GO; GO:0048705; P:skeletal system morphogenesis; IEA:Ensembl. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd10367; SH2_Src_Fgr; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR035693; Fgr_SH2. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF224; TYROSINE-PROTEIN KINASE FGR; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00452; SH3DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00252; SH2; 1. DR SMART; SM00326; SH3; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; P09769; HS. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell membrane; Cell projection; Cytoplasm; KW Cytoskeleton; Immunity; Innate immunity; Kinase; Lipoprotein; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Myristate; Nucleotide-binding; KW Palmitate; Phosphoprotein; Proto-oncogene; Reference proteome; SH2 domain; KW SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..529 FT /note="Tyrosine-protein kinase Fgr" FT /id="PRO_0000088091" FT DOMAIN 77..138 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 144..241 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 263..516 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ACT_SITE 382 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 269..277 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 291 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 34 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 208 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P14234" FT MOD_RES 218 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P14234" FT MOD_RES 412 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 523 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0007744|PubMed:19369195" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250" FT LIPID 3 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 6 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT VARIANT 110 FT /note="T -> I (in dbSNP:rs34597831)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041700" FT VARIANT 130 FT /note="S -> R (in dbSNP:rs35334091)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041701" FT MUTAGEN 523 FT /note="Y->F: Strongly increased catalytic activity. FT Functions as oncogene." FT /evidence="ECO:0000269|PubMed:1737799" FT STRAND 82..86 FT /evidence="ECO:0007829|PDB:7JT9" FT STRAND 92..95 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 103..108 FT /evidence="ECO:0007829|PDB:7JT9" FT STRAND 112..119 FT /evidence="ECO:0007829|PDB:7JT9" FT TURN 120..122 FT /evidence="ECO:0007829|PDB:7JT9" FT STRAND 125..129 FT /evidence="ECO:0007829|PDB:7JT9" FT HELIX 130..132 FT /evidence="ECO:0007829|PDB:7JT9" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:7JT9" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 151..158 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 167..172 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 180..188 FT /evidence="ECO:0007829|PDB:7UY0" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 192..202 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 204..206 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 208..211 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 219..228 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 231..235 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 249..252 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 260..262 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 263..271 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 273..282 FT /evidence="ECO:0007829|PDB:7UY0" FT TURN 283..285 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 286..293 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 300..310 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 321..325 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 327..329 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 331..334 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 342..345 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 349..352 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 356..375 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 388..390 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 392..394 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 396..398 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 403..406 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 407..412 FT /evidence="ECO:0007829|PDB:7UY3" FT HELIX 422..424 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 427..432 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 437..452 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 464..472 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 485..494 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 499..501 FT /evidence="ECO:0007829|PDB:7UY0" FT HELIX 505..513 FT /evidence="ECO:0007829|PDB:7UY0" FT TURN 514..516 FT /evidence="ECO:0007829|PDB:7UY0" FT STRAND 522..524 FT /evidence="ECO:0007829|PDB:7UY0" SQ SEQUENCE 529 AA; 59479 MW; 6B8C1E08414E0F9C CRC64; MGCVFCKKLE PVATAKEDAG LEGDFRSYGA ADHYGPDPTK ARPASSFAHI PNYSNFSSQA INPGFLDSGT IRGVSGIGVT LFIALYDYEA RTEDDLTFTK GEKFHILNNT EGDWWEARSL SSGKTGCIPS NYVAPVDSIQ AEEWYFGKIG RKDAERQLLS PGNPQGAFLI RESETTKGAY SLSIRDWDQT RGDHVKHYKI RKLDMGGYYI TTRVQFNSVQ ELVQHYMEVN DGLCNLLIAP CTIMKPQTLG LAKDAWEISR SSITLERRLG TGCFGDVWLG TWNGSTKVAV KTLKPGTMSP KAFLEEAQVM KLLRHDKLVQ LYAVVSEEPI YIVTEFMCHG SLLDFLKNPE GQDLRLPQLV DMAAQVAEGM AYMERMNYIH RDLRAANILV GERLACKIAD FGLARLIKDD EYNPCQGSKF PIKWTAPEAA LFGRFTIKSD VWSFGILLTE LITKGRIPYP GMNKREVLEQ VEQGYHMPCP PGCPASLYEA MEQTWRLDPE ERPTFEYLQS FLEDYFTSAE PQYQPGDQT //