FGFR2_NOTVI
ID FGFR2_NOTVI Reviewed; 729 AA.
AC Q91147;
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 Flags: Precursor;
GN Name=FGFR2;
OS Notophthalmus viridescens (Eastern newt) (Triturus viridescens).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Caudata; Salamandroidea; Salamandridae; Pleurodelinae;
OC Notophthalmus.
OX NCBI_TaxID=8316;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Regenerating forelimb blastema;
RX PubMed=8312364; DOI=10.1016/0167-4889(94)90137-6;
RA Poulin M.L., Chiu I.-M.;
RT "Nucleotide sequences of two newt (Notophthalmus viridescens) fibroblast
RT growth factor receptor-2 variants.";
RL Biochim. Biophys. Acta 1220:209-211(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; L19869; AAA49395.1; -; mRNA.
DR PIR; S41050; S41050.
DR AlphaFoldDB; Q91147; -.
DR SMR; Q91147; -.
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:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005007; F:fibroblast growth factor receptor activity; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:InterPro.
DR Gene3D; 2.60.40.10; -; 2.
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; 2.
DR SMART; SM00408; IGc2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
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..729
FT /note="Fibroblast growth factor receptor 2"
FT /id="PRO_0000249204"
FT TOPO_DOM 22..285
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..729
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 64..157
FT /note="Ig-like C2-type 1"
FT DOMAIN 166..268
FT /note="Ig-like C2-type 2"
FT DOMAIN 389..678
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 29..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 71..88
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT REGION 682..729
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..52
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 682..704
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 534
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 395..403
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 425
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 473..475
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 479
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 374
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 494
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 564
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 565
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 677
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
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 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 89..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 188..252
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 729 AA; 81825 MW; 931437A37C48C15F CRC64;
MFSWSYLMGL VMVATATLSL ARPSYNIAED TTLEPEDANS SGDDEDDNDG SEDFTNDNNH
MRAPYWTNTE KLEKKLHAVP AANTVKFRCP AGGNPTPSMR WLKNGKEFKQ EHRIGGFKVR
SQHFSLIMES VVPSDEGNYT CIMENEYGSI NHTYHLDVVE RSPHRPILQA GLPANTTTKV
GGDAEFVCKV YSDAQPHIQW IRHFELNGSK IGPDGHPYLK VLKAAGVNTT DKEIEVLYVR
NVSFEDAGEY TCLAGNSTGI SYHTAWLTVL PDEERELDSS SEYTEIAIYC VGGFLITCMI
GTIMVCHMKG RGKKSDFSSP PAVHKLSKSL PLRRQVTVSA DSSSSMNSNT PLVRITTRLS
SNNDTHLLAG VSEYELPEDP KWEYPREKLT LGKPLGEGCF GQVVMAEAVG IDKDRPKDAA
TVAVKMLKDD ATEKDLSDLV SEMEMMKMIG KHKNIINLLG ACTQDGPLYV IVEYASKGNL
REYLRTRRPP GMEYSFDINR IPEEQMTFKD LVSCTYQLAR GMEYLASQKC IHRDLAARNV
LVTETNVMKI ADFGLARDIN NIDYYKKTTN GRLPVKWMAP EALFDRVYTH QSDVWSFGVL
MWEIFTLGGS PYPGIPVEEL FKLLKEGHRM DKPGNCTNEL YTMMTDCWRA VPSQRPTFKQ
LVEDLDRILT QTTNEEYLDL NNPLEQYSPS YPDTRSSCSS GDDSVFSPDA MPYDPCLPKS
QHTNGTIKT
