FGFR2_PLEWA
ID FGFR2_PLEWA Reviewed; 824 AA.
AC Q91286;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Fibroblast growth factor receptor 2;
DE Short=FGFR-2;
DE EC=2.7.10.1;
DE AltName: Full=PFR2;
DE Flags: Precursor;
GN Name=FGFR2;
OS Pleurodeles waltl (Iberian ribbed newt).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Caudata; Salamandroidea; Salamandridae; Pleurodelinae;
OC Pleurodeles.
OX NCBI_TaxID=8319;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8026621; DOI=10.1006/dbio.1994.1189;
RA Shi D.-L., Launay C., Fromentoux V., Feige J.-J., Boucaut J.-C.;
RT "Expression of fibroblast growth factor receptor-2 splice variants is
RT developmentally and tissue-specifically regulated in the amphibian
RT embryo.";
RL Dev. Biol. 164:173-182(1994).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as 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, limb bud development, lung morphogenesis,
CC osteogenesis and skin development. Plays an essential role in the
CC regulation of osteoblast differentiation, proliferation and apoptosis,
CC and is required for normal skeleton development. Promotes cell
CC proliferation in keratinocytes and immature osteoblasts, but promotes
CC apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and
CC PAK4. Ligand binding leads to the activation of several signaling
CC cascades. Activation of PLCG1 leads to the production of the cellular
CC signaling 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 (By similarity). {ECO:0000250}.
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 (By similarity).
CC {ECO:0000250}.
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 -!- DOMAIN: The second and third Ig-like domains directly interact with
CC fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
CC {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 -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Fibroblast growth factor receptor subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; X74332; CAA52379.1; -; mRNA.
DR PIR; I51127; S36439.
DR AlphaFoldDB; Q91286; -.
DR SMR; Q91286; -.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017134; F:fibroblast growth factor binding; ISS:UniProtKB.
DR GO; GO:0005007; F:fibroblast growth factor receptor activity; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0060667; P:branch elongation involved in salivary gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0048755; P:branching morphogenesis of a nerve; ISS:UniProtKB.
DR GO; GO:0060449; P:bud elongation involved in lung branching; ISS:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; ISS:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; ISS:UniProtKB.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0048568; P:embryonic organ development; ISS:UniProtKB.
DR GO; GO:0048562; P:embryonic organ morphogenesis; ISS:UniProtKB.
DR GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB.
DR GO; GO:0048730; P:epidermis morphogenesis; ISS:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0060664; P:epithelial cell proliferation involved in salivary gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0022612; P:gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0042472; P:inner ear morphogenesis; ISS:UniProtKB.
DR GO; GO:0032808; P:lacrimal gland development; ISS:UniProtKB.
DR GO; GO:0060601; P:lateral sprouting from an epithelium; ISS:UniProtKB.
DR GO; GO:0060174; P:limb bud formation; ISS:UniProtKB.
DR GO; GO:0048286; P:lung alveolus development; ISS:UniProtKB.
DR GO; GO:0030324; P:lung development; ISS:UniProtKB.
DR GO; GO:0060463; P:lung lobe morphogenesis; ISS:UniProtKB.
DR GO; GO:0060484; P:lung-associated mesenchyme development; ISS:UniProtKB.
DR GO; GO:0003149; P:membranous septum morphogenesis; ISS:UniProtKB.
DR GO; GO:0048762; P:mesenchymal cell differentiation; ISS:UniProtKB.
DR GO; GO:0060915; P:mesenchymal cell differentiation involved in lung development; ISS:UniProtKB.
DR GO; GO:0060916; P:mesenchymal cell proliferation involved in lung development; ISS:UniProtKB.
DR GO; GO:0030901; P:midbrain development; ISS:UniProtKB.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; ISS:UniProtKB.
DR GO; GO:0035265; P:organ growth; ISS:UniProtKB.
DR GO; GO:0030916; P:otic vesicle formation; ISS:UniProtKB.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; ISS:UniProtKB.
DR GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; ISS:UniProtKB.
DR GO; GO:0060523; P:prostate epithelial cord elongation; ISS:UniProtKB.
DR GO; GO:0060512; P:prostate gland morphogenesis; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0060688; P:regulation of morphogenesis of a branching structure; ISS:UniProtKB.
DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0048608; P:reproductive structure development; ISS:UniProtKB.
DR GO; GO:0060529; P:squamous basal epithelial stem cell differentiation involved in prostate gland acinus development; ISS:UniProtKB.
DR GO; GO:0001657; P:ureteric bud development; ISS:UniProtKB.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 3.
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 Pfam; PF07679; I-set; 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; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 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 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell membrane; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Immunoglobulin domain; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..824
FT /note="Fibroblast growth factor receptor 2"
FT /id="PRO_0000249217"
FT TOPO_DOM 22..374
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 396..824
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..125
FT /note="Ig-like C2-type 1"
FT DOMAIN 153..246
FT /note="Ig-like C2-type 2"
FT DOMAIN 254..356
FT /note="Ig-like C2-type 3"
FT DOMAIN 478..767
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 125..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 160..177
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT REGION 801..824
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 803..817
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 623
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 484..492
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 514
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 562..564
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 568
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 463
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 583
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 653
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 654
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 766
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
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 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 62..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 178..230
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 277..340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 824 AA; 92307 MW; 58B39786746D620B CRC64;
MFSWSYLMGL VMVATATLSL ARPSYNIAED TTLEPEEPPT KYQISQPDVH SALPGESVEL
RCLLGDAIMV TWTKDGAQLV SNNRTLLIGP YLQIREAAPR DSGLYACGAT RPLQSETRYF
IVNITDGNSS GDDEDDNDGS EDFTNDNNHK RAPYWTNTEK LEKKLHAVPA ANTVKFRCPA
GGNPLPSMRW LKNGKEFKQE HRIGGFKVRS QHWSLIMESV VPSDKGNYTC IMENEYGSIN
HTYHLDVVER SPHPPILQAG LPANTTTKVG GDREFVCKVY SDAQPHIQWR HIELNGSKIG
PDGNPYLKVL KAAGGNTTVK EIEVLYVRNV SFEDAGEYTC LAGNSIGISY HSAWLTVLPD
EERQLDSSSS EYTEIAIYCV GGFLIACMIG TIMMCHMKGR GKKSDFSSQP AVHKLSKRLP
LRRQVTVSAD SSSSMNSNTP LVRITTRLLS NTDTHLLAGV SEYELPEDPK WEYPRDKLTL
GKPLGEGCFG QVVMAEAVGI DKDRPKDAVT VAVKMLKDDA TEKDLSDLVS EMEMMKMIGK
HKNIINLLGA CTQDGPLYVI VEYASKGNLR EYLRTRRPPG MEYSFDIFRI PEEQMTFKDL
VSCTYQLARG MEYLASQKCI HRDLAARNVL VTETNVIKIA DFGLARDINN IDYYKKTTNG
RLPVKWMAPE ALFDRVYTLQ SDVWSFGVLM WEIFTLGGSP YPGIPVEELF KLLKEGHRMV
KPGNCTNELY TMMTDCWRAV PSQRPTFKQL VEDLDRILTQ TTNEEYLDLN NPLEPYSPSY
PDTRSSCSFG DDSVFSPDPM SMNLAFPNPN TQMAPLKHEA TQPA
