ID FGFR2_MOUSE Reviewed; 821 AA. AC P21803; O55141; Q00389; Q61342; DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 4. DT 27-MAR-2024, entry version 207. DE RecName: Full=Fibroblast growth factor receptor 2; DE Short=FGFR-2; DE EC=2.7.10.1; DE AltName: Full=Keratinocyte growth factor receptor; DE Short=KGFR; DE AltName: CD_antigen=CD332; DE Flags: Precursor; GN Name=Fgfr2; Synonyms=Bek, Ect1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC STRAIN=BALB/cJ; TISSUE=Brain; RX PubMed=1711190; RA Raz V., Kelman Z., Avivi A., Neufeld G., Givol D., Yarden Y.; RT "PCR-based identification of new receptors: molecular cloning of a receptor RT for fibroblast growth factors."; RL Oncogene 6:753-760(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RX PubMed=1846048; DOI=10.1126/science.1846048; RA Miki T., Fleming T.P., Bottaro D.P., Rubin J.S., Ron D., Aaronson S.A.; RT "Expression cDNA cloning of the KGF receptor by creation of a transforming RT autocrine loop."; RL Science 251:72-75(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC TISSUE=Brain, and Liver; RX PubMed=1373495; DOI=10.1073/pnas.89.8.3305; RA Mansukhani A., Dell'Era P., Moscatelli D., Kornbluth S., Hanafusa H., RA Basilico C.; RT "Characterization of the murine BEK fibroblast growth factor (FGF) RT receptor: activation by three members of the FGF family and requirement for RT heparin."; RL Proc. Natl. Acad. Sci. U.S.A. 89:3305-3309(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM LONG). RX PubMed=9499422; DOI=10.1093/hmg/7.4.685; RA Twigg S.R.F., Burns H.D., Oldridge M., Heath J.K., Wilkie A.O.M.; RT "Conserved use of a non-canonical 5' splice site (/GA) in alternative RT splicing by fibroblast growth factor receptors 1, 2 and 3."; RL Hum. Mol. Genet. 7:685-691(1998). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 477-821. RC TISSUE=Liver; RX PubMed=2468999; DOI=10.1128/mcb.8.12.5541-5544.1988; RA Kornbluth S., Paulson K.E., Hanafusa H.; RT "Novel tyrosine kinase identified by phosphotyrosine antibody screening of RT cDNA libraries."; RL Mol. Cell. Biol. 8:5541-5544(1988). RN [6] RP FUNCTION. RX PubMed=8393815; DOI=10.1006/dbio.1993.1205; RA Orr-Urtreger A., Bedford M.T., Burakova T., Arman E., Zimmer Y., Yayon A., RA Givol D., Lonai P.; RT "Developmental localization of the splicing alternatives of fibroblast RT growth factor receptor-2 (FGFR2)."; RL Dev. Biol. 158:475-486(1993). RN [7] RP INTERACTION WITH FGF1; FGF2; FGF3; FGF4; FGF6; FGF7 AND FGF9, AND FUNCTION RP IN CELL PROLIFERATION. RX PubMed=8663044; DOI=10.1074/jbc.271.25.15292; RA Ornitz D.M., Xu J., Colvin J.S., McEwen D.G., MacArthur C.A., Coulier F., RA Gao G., Goldfarb M.; RT "Receptor specificity of the fibroblast growth factor family."; RL J. Biol. Chem. 271:15292-15297(1996). RN [8] RP DISRUPTION PHENOTYPE. RX PubMed=9435295; DOI=10.1242/dev.125.4.753; RA Xu X., Weinstein M., Li C., Naski M., Cohen R.I., Ornitz D.M., Leder P., RA Deng C.; RT "Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation RT loop between FGF8 and FGF10 is essential for limb induction."; RL Development 125:753-765(1998). RN [9] RP DISRUPTION PHENOTYPE. RX PubMed=9560232; DOI=10.1073/pnas.95.9.5082; RA Arman E., Haffner-Krausz R., Chen Y., Heath J.K., Lonai P.; RT "Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests RT a role for FGF signaling in pregastrulation mammalian development."; RL Proc. Natl. Acad. Sci. U.S.A. 95:5082-5087(1998). RN [10] RP DISRUPTION PHENOTYPE. RX PubMed=10518547; DOI=10.1073/pnas.96.21.11895; RA Arman E., Haffner-Krausz R., Gorivodsky M., Lonai P.; RT "Fgfr2 is required for limb outgrowth and lung-branching morphogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11895-11899(1999). RN [11] RP FUNCTION. RX PubMed=10851026; DOI=10.1083/jcb.149.6.1297; RA Mansukhani A., Bellosta P., Sahni M., Basilico C.; RT "Signaling by fibroblast growth factors (FGF) and fibroblast growth factor RT receptor 2 (FGFR2)-activating mutations blocks mineralization and induces RT apoptosis in osteoblasts."; RL J. Cell Biol. 149:1297-1308(2000). RN [12] RP DISRUPTION PHENOTYPE. RX PubMed=12135917; DOI=10.1242/dev.129.16.3783; RA Eswarakumar V.P., Monsonego-Ornan E., Pines M., Antonopoulou I., RA Morriss-Kay G.M., Lonai P.; RT "The IIIc alternative of Fgfr2 is a positive regulator of bone formation."; RL Development 129:3783-3793(2002). RN [13] RP FUNCTION IN CELL PROLIFERATION AND ACTIVATION OF SIGNALING PATHWAYS, RP MUTAGENESIS OF TYR-769, PHOSPHORYLATION AT TYR-769, AND INTERACTION WITH RP PLCG1. RX PubMed=15629145; DOI=10.1016/j.bbrc.2004.12.031; RA Ceridono M., Belleudi F., Ceccarelli S., Torrisi M.R.; RT "Tyrosine 769 of the keratinocyte growth factor receptor is required for RT receptor signaling but not endocytosis."; RL Biochem. Biophys. Res. Commun. 327:523-532(2005). RN [14] RP INTERACTION WITH FLRT2. RX PubMed=21765038; DOI=10.1177/0022034511415272; RA Wei K., Xu Y., Tse H., Manolson M.F., Gong S.G.; RT "Mouse FLRT2 interacts with the extracellular and intracellular regions of RT FGFR2."; RL J. Dent. Res. 90:1234-1239(2011). CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor CC for fibroblast growth factors and plays an essential role in the CC regulation of cell proliferation, differentiation, migration and CC apoptosis, and in the regulation of embryonic development. Required for CC normal embryonic patterning, trophoblast function, limb bud CC development, lung morphogenesis, osteogenesis and skin development. CC Plays an essential role in the regulation of osteoblast CC differentiation, proliferation and apoptosis, and is required for CC normal skeleton development. Promotes cell proliferation in CC keratinocytes and immature osteoblasts, but promotes apoptosis in CC differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand CC binding leads to the activation of several signaling cascades. CC Activation of PLCG1 leads to the production of the cellular signaling CC molecules diacylglycerol and inositol 1,4,5-trisphosphate. CC Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and CC SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the CC MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. CC FGFR2 signaling is down-regulated by ubiquitination, internalization CC and degradation. Mutations that lead to constitutive kinase activation CC or impair normal FGFR2 maturation, internalization and degradation lead CC to aberrant signaling. Over-expressed FGFR2 promotes activation of CC STAT1. {ECO:0000269|PubMed:10851026, ECO:0000269|PubMed:15629145, CC ECO:0000269|PubMed:8393815, ECO:0000269|PubMed:8663044}. 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=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence CC of bound ligand. Ligand binding leads to dimerization and activation by CC autophosphorylation on tyrosine residues (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Monomer. Homodimer after ligand binding. Interacts CC predominantly with FGF1 and FGF2, but can also interact with FGF3, CC FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro) CC (PubMed:8663044). Ligand specificity is determined by tissue-specific CC expression of isoforms, and differences in the third Ig-like domain are CC crucial for ligand specificity. Affinity for fibroblast growth factors CC (FGFs) is increased by heparan sulfate glycosaminoglycans that function CC as coreceptors. Likewise, KLB increases the affinity for FGF19 and CC FGF21. Interacts with PLCG1 (PubMed:15629145). Interacts with GRB2 and CC PAK4 (By similarity). Interacts with FLRT2 (PubMed:21765038). CC {ECO:0000250|UniProtKB:P21802, ECO:0000269|PubMed:15629145, CC ECO:0000269|PubMed:21765038, ECO:0000269|PubMed:8663044}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. Golgi apparatus {ECO:0000250}. Cytoplasmic vesicle CC {ECO:0000250}. Note=Detected on osteoblast plasma membrane lipid rafts. CC After ligand binding, the activated receptor is rapidly internalized CC and degraded (By similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P21803-1; Sequence=Displayed; CC Name=Short; CC IsoId=P21803-2; Sequence=VSP_002985, VSP_002986, VSP_002987; CC -!- DOMAIN: The second and third Ig-like domains directly interact with CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans. CC Alternative splicing events affecting the third Ig-like domain are CC crucial for ligand selectivity (By similarity). {ECO:0000250}. CC -!- PTM: Autophosphorylated. Binding of FGF family members together with CC heparan sulfate proteoglycan or heparin promotes receptor dimerization CC and autophosphorylation on tyrosine residues. Autophosphorylation CC occurs in trans between the two FGFR molecules present in the dimer (By CC similarity). {ECO:0000250}. CC -!- PTM: N-glycosylated in the endoplasmic reticulum. The N-glycan chains CC undergo further maturation to an Endo H-resistant form in the Golgi CC apparatus (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated. FGFR2 is rapidly ubiquitinated after CC autophosphorylation, leading to internalization and degradation. CC Subject to degradation both in lysosomes and by the proteasome (By CC similarity). {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Embryonic lethality shortly after implantation, CC due to trophoblast defects, absence of a functional placenta, failure CC of limb bud formation, plus defects in lung branching and heart CC development. {ECO:0000269|PubMed:10518547, ECO:0000269|PubMed:12135917, CC ECO:0000269|PubMed:9435295, ECO:0000269|PubMed:9560232}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Fibroblast growth factor receptor subfamily. CC {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; X55441; CAA39083.1; -; mRNA. DR EMBL; M63503; AAA39377.1; -; mRNA. DR EMBL; M86441; AAA37286.1; -; mRNA. DR EMBL; Y16152; CAA76098.1; -; Genomic_DNA. DR EMBL; Y16167; CAA76099.1; -; Genomic_DNA. DR EMBL; M23362; AAA37285.1; -; mRNA. DR PIR; A38429; A38429. DR PIR; A44142; TVMSBK. DR PIR; S17295; S17295. DR RefSeq; NP_034337.2; NM_010207.2. DR RefSeq; NP_963895.2; NM_201601.2. DR PDB; 4HWU; X-ray; 2.90 A; A/B=45-127. DR PDBsum; 4HWU; -. DR AlphaFoldDB; P21803; -. DR SMR; P21803; -. DR BioGRID; 199657; 20. DR DIP; DIP-6038N; -. DR IntAct; P21803; 2. DR STRING; 10090.ENSMUSP00000112430; -. DR ChEMBL; CHEMBL3648; -. DR GlyCosmos; P21803; 9 sites, No reported glycans. DR GlyGen; P21803; 10 sites, 1 O-linked glycan (1 site). DR iPTMnet; P21803; -. DR PhosphoSitePlus; P21803; -. DR CPTAC; non-CPTAC-3806; -. DR jPOST; P21803; -. DR MaxQB; P21803; -. DR PaxDb; 10090-ENSMUSP00000112430; -. DR ProteomicsDB; 271890; -. [P21803-1] DR ProteomicsDB; 271891; -. [P21803-2] DR Pumba; P21803; -. DR ABCD; P21803; 1 sequenced antibody. DR DNASU; 14183; -. DR GeneID; 14183; -. DR KEGG; mmu:14183; -. DR AGR; MGI:95523; -. DR CTD; 2263; -. DR MGI; MGI:95523; Fgfr2. DR eggNOG; KOG0200; Eukaryota. DR InParanoid; P21803; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P21803; -. DR BRENDA; 2.7.10.1; 3474. DR Reactome; R-MMU-109704; PI3K Cascade. DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling. DR Reactome; R-MMU-190375; FGFR2c ligand binding and activation. DR Reactome; R-MMU-190377; FGFR2b ligand binding and activation. DR Reactome; R-MMU-5654221; Phospholipase C-mediated cascade, FGFR2. DR Reactome; R-MMU-5654695; PI-3K cascade:FGFR2. DR Reactome; R-MMU-5654699; SHC-mediated cascade:FGFR2. DR Reactome; R-MMU-5654700; FRS-mediated FGFR2 signaling. DR Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR BioGRID-ORCS; 14183; 5 hits in 79 CRISPR screens. DR ChiTaRS; Fgfr2; mouse. DR PRO; PR:P21803; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P21803; Protein. DR GO; GO:0005938; C:cell cortex; ISO:MGI. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0060076; C:excitatory synapse; IMP:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:MGI. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0017134; F:fibroblast growth factor binding; IDA:MGI. DR GO; GO:0005007; F:fibroblast growth factor receptor activity; ISO:MGI. DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI. DR GO; GO:0001525; P:angiogenesis; IGI:MGI. DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI. DR GO; GO:0007409; P:axonogenesis; IMP:MGI. DR GO; GO:0060348; P:bone development; IMP:MGI. DR GO; GO:0030282; P:bone mineralization; IMP:MGI. DR GO; GO:0060349; P:bone morphogenesis; IMP:MGI. DR GO; GO:0060667; P:branch elongation involved in salivary gland morphogenesis; IMP:MGI. DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IMP:MGI. DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IMP:MGI. DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IMP:MGI. DR GO; GO:0048755; P:branching morphogenesis of a nerve; IMP:MGI. DR GO; GO:0060449; P:bud elongation involved in lung branching; IMP:MGI. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:MGI. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IGI:MGI. DR GO; GO:0051301; P:cell division; IMP:MGI. DR GO; GO:0045165; P:cell fate commitment; IDA:MGI. DR GO; GO:0008283; P:cell population proliferation; IMP:MGI. DR GO; GO:0007267; P:cell-cell signaling; IMP:MGI. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISO:MGI. DR GO; GO:0060365; P:coronal suture morphogenesis; IMP:MGI. DR GO; GO:0048565; P:digestive tract development; IMP:MGI. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISO:MGI. DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IMP:MGI. DR GO; GO:0048568; P:embryonic organ development; IMP:MGI. DR GO; GO:0048562; P:embryonic organ morphogenesis; IMP:MGI. DR GO; GO:0009880; P:embryonic pattern specification; IMP:MGI. DR GO; GO:0061031; P:endodermal digestive tract morphogenesis; IMP:MGI. DR GO; GO:0048730; P:epidermis morphogenesis; IMP:MGI. DR GO; GO:0030855; P:epithelial cell differentiation; IMP:MGI. DR GO; GO:0050673; P:epithelial cell proliferation; IMP:MGI. DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; IMP:MGI. DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:MGI. DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IMP:MGI. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IGI:MGI. DR GO; GO:1902178; P:fibroblast growth factor receptor apoptotic signaling pathway; IMP:MGI. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IMP:MGI. DR GO; GO:0035603; P:fibroblast growth factor receptor signaling pathway involved in hemopoiesis; IMP:UniProtKB. DR GO; GO:0060595; P:fibroblast growth factor receptor signaling pathway involved in mammary gland specification; IMP:MGI. DR GO; GO:0035602; P:fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell; IMP:UniProtKB. DR GO; GO:0035607; P:fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development; IMP:UniProtKB. DR GO; GO:0035604; P:fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow; IMP:UniProtKB. DR GO; GO:0022612; P:gland morphogenesis; IMP:MGI. DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI. DR GO; GO:0032808; P:lacrimal gland development; IMP:MGI. DR GO; GO:0060601; P:lateral sprouting from an epithelium; IMP:MGI. DR GO; GO:0070307; P:lens fiber cell development; IMP:MGI. DR GO; GO:0060174; P:limb bud formation; IMP:MGI. DR GO; GO:0048286; P:lung alveolus development; IMP:MGI. DR GO; GO:0030324; P:lung development; IMP:MGI. DR GO; GO:0060463; P:lung lobe morphogenesis; IMP:MGI. DR GO; GO:0060484; P:lung-associated mesenchyme development; IMP:MGI. DR GO; GO:0060615; P:mammary gland bud formation; IMP:MGI. DR GO; GO:0003149; P:membranous septum morphogenesis; IMP:MGI. DR GO; GO:0048762; P:mesenchymal cell differentiation; IGI:MGI. DR GO; GO:0060915; P:mesenchymal cell differentiation involved in lung development; IGI:MGI. DR GO; GO:0010463; P:mesenchymal cell proliferation; IGI:MGI. DR GO; GO:0060916; P:mesenchymal cell proliferation involved in lung development; IMP:MGI. DR GO; GO:0030901; P:midbrain development; IGI:MGI. DR GO; GO:0140014; P:mitotic nuclear division; IGI:MGI. DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IMP:MGI. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IGI:MGI. DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; ISO:MGI. DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; IGI:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0007528; P:neuromuscular junction development; IMP:MGI. DR GO; GO:0042476; P:odontogenesis; IMP:MGI. DR GO; GO:0021769; P:orbitofrontal cortex development; IMP:UniProtKB. DR GO; GO:0035265; P:organ growth; IMP:MGI. DR GO; GO:0030916; P:otic vesicle formation; IMP:MGI. DR GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:MGI. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:MGI. DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IGI:MGI. DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB. DR GO; GO:0051781; P:positive regulation of cell division; IMP:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI. DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; IMP:MGI. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IGI:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IGI:MGI. DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0050677; P:positive regulation of urothelial cell proliferation; IMP:MGI. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; ISO:MGI. DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:MGI. DR GO; GO:0009791; P:post-embryonic development; IMP:MGI. DR GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IMP:MGI. DR GO; GO:0060523; P:prostate epithelial cord elongation; IMP:MGI. DR GO; GO:0060512; P:prostate gland morphogenesis; IMP:MGI. DR GO; GO:0021860; P:pyramidal neuron development; IMP:UniProtKB. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:MGI. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:MGI. DR GO; GO:0060688; P:regulation of morphogenesis of a branching structure; IMP:MGI. DR GO; GO:0033688; P:regulation of osteoblast proliferation; IMP:MGI. DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; IMP:MGI. DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IMP:MGI. DR GO; GO:0048608; P:reproductive structure development; IMP:MGI. DR GO; GO:0060529; P:squamous basal epithelial stem cell differentiation involved in prostate gland acinus development; IMP:MGI. DR GO; GO:0048863; P:stem cell differentiation; IGI:MGI. DR GO; GO:0072089; P:stem cell proliferation; IMP:MGI. DR GO; GO:0048489; P:synaptic vesicle transport; IMP:MGI. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR GO; GO:0001657; P:ureteric bud development; IGI:MGI. DR GO; GO:0050674; P:urothelial cell proliferation; IMP:MGI. DR GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; TAS:DFLAT. DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:MGI. DR GO; GO:0021847; P:ventricular zone neuroblast division; IMP:UniProtKB. DR CDD; cd05857; IgI_2_FGFR; 1. DR CDD; cd05858; IgI_3_FGFR2; 1. DR CDD; cd05101; PTKc_FGFR2; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR016248; FGF_rcpt_fam. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. 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; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR PANTHER; PTHR24416:SF130; FIBROBLAST GROWTH FACTOR RECEPTOR 2; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF07679; I-set; 1. DR Pfam; PF13927; Ig_3; 2. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PIRSF; PIRSF000628; FGFR; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00409; IG; 3. DR SMART; SM00408; IGc2; 3. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; Immunoglobulin; 3. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50835; IG_LIKE; 3. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell membrane; KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Golgi apparatus; KW Heparin-binding; Immunoglobulin domain; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor; KW Reference proteome; Repeat; Signal; Transferase; Transmembrane; KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1..21 FT CHAIN 22..821 FT /note="Fibroblast growth factor receptor 2" FT /id="PRO_0000016784" FT TOPO_DOM 22..377 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 378..398 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 399..821 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 25..125 FT /note="Ig-like C2-type 1" FT DOMAIN 154..247 FT /note="Ig-like C2-type 2" FT DOMAIN 256..358 FT /note="Ig-like C2-type 3" FT DOMAIN 481..770 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 129..151 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 161..178 FT /note="Heparin-binding" FT /evidence="ECO:0000250" FT ACT_SITE 626 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 487..495 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 517 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 565..567 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 571 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 466 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P21802" FT MOD_RES 586 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P21802" FT MOD_RES 588 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P21802" FT MOD_RES 656 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P21802" FT MOD_RES 657 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P21802" FT MOD_RES 769 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P21802" FT MOD_RES 780 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P21802" FT CARBOHYD 83 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 123 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 147 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 228 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 241 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 265 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 297 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 318 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 331 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 62..107 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 179..231 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 278..342 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 37 FT /note="E -> G (in isoform Short)" FT /evidence="ECO:0000303|PubMed:1846048" FT /id="VSP_002985" FT VAR_SEQ 38..152 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:1846048" FT /id="VSP_002986" FT VAR_SEQ 314..361 FT /note="AAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVLP -> FT HSGINSSNAEVLALFNVTEMDAGEYICKVSNYIGQANQSAWLTVLPKQQ (in FT isoform Short)" FT /evidence="ECO:0000303|PubMed:1846048" FT /id="VSP_002987" FT MUTAGEN 769 FT /note="Y->F: Abolishes phosphorylation of FRS2 and FT activation of MAP kinases." FT /evidence="ECO:0000269|PubMed:15629145" FT CONFLICT 53 FT /note="A -> V (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 55..56 FT /note="GE -> RG (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 90 FT /note="E -> R (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 119 FT /note="I -> Y (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 142..143 FT /note="DV -> R (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 169 FT /note="C -> V (in Ref. 1; CAA39083 and 2; AAA39377)" FT /evidence="ECO:0000305" FT CONFLICT 187 FT /note="S -> P (in Ref. 1; CAA39083 and 2; AAA39377)" FT /evidence="ECO:0000305" FT CONFLICT 214 FT /note="W -> R (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 229 FT /note="Y -> I (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 275 FT /note="E -> R (in Ref. 1; CAA39083)" FT /evidence="ECO:0000305" FT CONFLICT 301 FT /note="N -> Y (in Ref. 1; CAA39083 and 2; AAA39377)" FT /evidence="ECO:0000305" FT STRAND 48..52 FT /evidence="ECO:0007829|PDB:4HWU" FT STRAND 58..61 FT /evidence="ECO:0007829|PDB:4HWU" FT STRAND 69..74 FT /evidence="ECO:0007829|PDB:4HWU" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:4HWU" FT STRAND 83..88 FT /evidence="ECO:0007829|PDB:4HWU" FT STRAND 91..94 FT /evidence="ECO:0007829|PDB:4HWU" FT HELIX 99..101 FT /evidence="ECO:0007829|PDB:4HWU" FT STRAND 103..110 FT /evidence="ECO:0007829|PDB:4HWU" FT STRAND 115..124 FT /evidence="ECO:0007829|PDB:4HWU" SQ SEQUENCE 821 AA; 91984 MW; FCDB28ADD61F4414 CRC64; MVSWGRFICL VLVTMATLSL ARPSFSLVED TTLEPEEPPT KYQISQPEAY VVAPGESLEL QCMLKDAAVI SWTKDGVHLG PNNRTVLIGE YLQIKGATPR DSGLYACTAA RTVDSETWIF MVNVTDAISS GDDEDDTDSS EDVVSENRSN QRAPYWTNTE KMEKRLHACP AANTVKFRCP AGGNPTSTMR WLKNGKEFKQ EHRIGGYKVR NQHWSLIMES VVPSDKGNYT CLVENEYGSI NHTYHLDVVE RSPHRPILQA GLPANASTVV GGDVEFVCKV YSDAQPHIQW IKHVEKNGSK NGPDGLPYLK VLKAAGVNTT DKEIEVLYIR NVTFEDAGEY TCLAGNSIGI SFHSAWLTVL PAPVREKEIT ASPDYLEIAI YCIGVFLIAC MVVTVIFCRM KTTTKKPDFS SQPAVHKLTK RIPLRRQVTV SAESSSSMNS NTPLVRITTR LSSTADTPML AGVSEYELPE DPKWEFPRDK LTLGKPLGEG CFGQVVMAEA VGIDKDKPKE AVTVAVKMLK DDATEKDLSD LVSEMEMMKM IGKHKNIINL LGACTQDGPL YVIVEYASKG NLREYLRARR PPGMEYSYDI NRVPEEQMTF KDLVSCTYQL ARGMEYLASQ KCIHRDLAAR NVLVTENNVM KIADFGLARD INNIDYYKKT TNGRLPVKWM APEALFDRVY THQSDVWSFG VLMWEIFTLG GSPYPGIPVE ELFKLLKEGH RMDKPTNCTN ELYMMMRDCW HAVPSQRPTF KQLVEDLDRI LTLTTNEEYL DLTQPLEQYS PSYPDTSSSC SSGDDSVFSP DPMPYEPCLP QYPHINGSVK T //