FGFR2_DANRE
ID FGFR2_DANRE Reviewed; 817 AA.
AC Q8JG38;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 129.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kaps C., Schlombs K., Kraus B., Odenthal J., Langheinrich U., Trowe T.;
RT "Cloning and characterization of zebrafish fibroblast growth factor
RT receptor 2 (Z-FGFR2): role of FGFR2-signaling in bone development.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
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 -!- INTERACTION:
CC Q8JG38; B3DGS1: fgfrl1b; NbExp=2; IntAct=EBI-2268234, EBI-2268218;
CC Q8JG38; A8BB40: lrrtm4l1; NbExp=2; IntAct=EBI-2268234, EBI-2263384;
CC Q8JG38; A4JYE7: vstm4b; NbExp=2; IntAct=EBI-2268234, EBI-2268137;
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; AJ309303; CAC84705.1; -; mRNA.
DR AlphaFoldDB; Q8JG38; -.
DR SMR; Q8JG38; -.
DR IntAct; Q8JG38; 3.
DR STRING; 7955.ENSDARP00000075360; -.
DR PaxDb; Q8JG38; -.
DR PRIDE; Q8JG38; -.
DR ZFIN; ZDB-GENE-030323-1; fgfr2.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q8JG38; -.
DR PhylomeDB; Q8JG38; -.
DR Reactome; R-DRE-109704; PI3K Cascade.
DR Reactome; R-DRE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DRE-190375; FGFR2c ligand binding and activation.
DR Reactome; R-DRE-190377; FGFR2b ligand binding and activation.
DR Reactome; R-DRE-5654221; Phospholipase C-mediated cascade, FGFR2.
DR Reactome; R-DRE-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-DRE-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-DRE-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-DRE-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-DRE-5673001; RAF/MAP kinase cascade.
DR Reactome; R-DRE-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR SignaLink; Q8JG38; -.
DR PRO; PR:Q8JG38; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:ZFIN.
DR GO; GO:0005007; F:fibroblast growth factor receptor activity; IBA:GO_Central.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0033278; P:cell proliferation in midbrain; IMP:ZFIN.
DR GO; GO:0060271; P:cilium assembly; IMP:ZFIN.
DR GO; GO:0061371; P:determination of heart left/right asymmetry; IMP:ZFIN.
DR GO; GO:0003140; P:determination of left/right asymmetry in lateral mesoderm; IMP:ZFIN.
DR GO; GO:0071910; P:determination of liver left/right asymmetry; IMP:ZFIN.
DR GO; GO:0035469; P:determination of pancreatic left/right asymmetry; IMP:ZFIN.
DR GO; GO:0048565; P:digestive tract development; IMP:ZFIN.
DR GO; GO:0030901; P:midbrain development; IMP:ZFIN.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:InterPro.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; IMP:ZFIN.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; 3.
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 1: Evidence at protein level;
KW Apoptosis; ATP-binding; Cell membrane; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Immunoglobulin domain; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..817
FT /note="Fibroblast growth factor receptor 2"
FT /id="PRO_0000249203"
FT TOPO_DOM 23..377
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..817
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 26..126
FT /note="Ig-like C2-type 1"
FT DOMAIN 159..247
FT /note="Ig-like C2-type 2"
FT DOMAIN 256..358
FT /note="Ig-like C2-type 3"
FT DOMAIN 477..766
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 161..178
FT /note="Heparin-binding"
FT /evidence="ECO:0000250"
FT REGION 429..465
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..465
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 622
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 483..491
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 513
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 561..563
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 567
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 462
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 582
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 652
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 765
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
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 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 63..108
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"
SQ SEQUENCE 817 AA; 91388 MW; 0A6D9F5412B27D69 CRC64;
MFARGWLLGA LLLMTLATVS VARPSLKIDL VNTSAPEEPP TKNQNCVPVL FSVHPGELLK
LKCPLSGADD VVWTKDSSSL RPDNRTLVAR DWLQISDATP KDSGLYSCSA TGLRDCDVFS
FIVNVTDAIS SGDDEDDTER SDDVGADGEQ MRLPYWTFPE KMEKKLHAVP AANTVKFRCA
AAGNPKPKMR WLKNAKPFRQ EDRMGGYKVR LQHWTLIMES VVPSDKGNYT CLVENQYGSI
DHTYTLDVVE RSPHRPILQA GLPANVTVQV GQDAKFVCKV YSDAQPHIQW LQHYTKNGSC
CGPDGLPYVR VLKTAGVNTT DKEIEVLYLP NVTFEDAGEY TCLAGNSIGI SYHTAWLTVH
PAETNPIETD YPPDYVEIAI YCIGVFLIAC MVVIVVVCRM RTSAKKPDFS SQPAVHKLTK
QIPLRRQVTV SSDSSSSMSS STPLVRITTR RSSAHDDPIP EYDLPEDPRW EFSRDKLTLG
KPLGEGCFGQ VVMAEALGID KDKPKEAVTV AVKMLKDDAT EKDLSDLVSE MEMMKMIGRH
KNIINLLGAC TQDGPLYVIV EYASKGNLRE YLRARRPPGM EYSYDIARVS DEPLTFKDLV
SCTYQVARGM EYLASQKCIH RDLAARNVLV TESNVMKIAD FGLARDVHNI DYYKKTTNGR
LPVKWMAPEA LFDRVYTHQS DVWSFGVLMW EIFTLGGSPY PGIPVEELFK LLKEGHRMDK
PANCTNELYM MMKDCWHAIS SHRPTFKQLV EDLDRILTLA TNEEYLDLCA PVEQYSPSFP
DTRSSCPSGD DSVFSHDPLA DEPCLPKYQH INGGIKT
