FGR_HUMAN
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 03-AUG-2022, entry version 227.
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 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
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}.
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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 PDBsum; 7JT9; -.
DR AlphaFoldDB; P09769; -.
DR SMR; P09769; -.
DR BioGRID; 108559; 80.
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 iPTMnet; P09769; -.
DR PhosphoSitePlus; P09769; -.
DR SwissPalm; P09769; -.
DR BioMuta; FGR; -.
DR DMDM; 125358; -.
DR CPTAC; CPTAC-1786; -.
DR EPD; P09769; -.
DR jPOST; P09769; -.
DR MassIVE; P09769; -.
DR MaxQB; P09769; -.
DR PaxDb; P09769; -.
DR PeptideAtlas; P09769; -.
DR PRIDE; P09769; -.
DR ProteomicsDB; 52268; -.
DR Antibodypedia; 711; 575 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 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; AQIPNYN; -.
DR OrthoDB; 539311at2759; -.
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; 12 hits in 1099 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 120 other tissues.
DR ExpressionAtlas; P09769; baseline and differential.
DR Genevisible; P09769; HS.
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: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:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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; -; 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 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; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 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.
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 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"
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
