ID FGFR3_PLEWA Reviewed; 796 AA.
AC Q91287;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 24-JAN-2024, entry version 114.
DE RecName: Full=Fibroblast growth factor receptor 3;
DE Short=FGFR-3;
DE EC=2.7.10.1;
DE AltName: Full=PFR3;
DE Flags: Precursor;
GN Name=FGFR3;
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], AND DEVELOPMENTAL STAGE.
RX PubMed=8006062; DOI=10.1242/jcs.107.3.417;
RA Shi D.-L., Fromentoux V., Launay C., Umbhauer M., Boucaut J.-C.;
RT "Isolation and developmental expression of the amphibian homolog of the
RT fibroblast growth factor receptor 3.";
RL J. Cell Sci. 107:417-425(1994).
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 and apoptosis. Plays
CC an essential role in the regulation of chondrocyte differentiation,
CC proliferation and apoptosis, and is required for normal skeleton
CC development. Regulates both osteogenesis and postnatal bone
CC mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but
CC can also promote cancer cell proliferation. Phosphorylates PLCG1, CBL
CC and FRS2. 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 (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 {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Undetectable in the adult skeletal muscle. Low
CC levels of expression were detected in the liver, lung and kidney.
CC Medium levels of expression were detected in the heart, spleen,
CC intestine and eye. Highest expression is observed in the testis.
CC -!- DEVELOPMENTAL STAGE: Maternally transcript whose a low level of
CC expression persists during the cleavage and gastrula stages and a
CC significant increase was observed at the end of the gastrula stage.
CC Mainly localized to the ectoderm at the early gastrula stage and then
CC shifted to the embryonic neural tissues, whereas adult brain had
CC decreased levels of expression. Strong expression in the germinal
CC epithelium of the embryonic brain (especially the diencephalon and
CC rhombencephalon) and neural tube, in the lens and the cranial ganglia.
CC The epithelium of the developing gut, like the pharynx and esophagus,
CC also prominently expressed it. Other sites of expression were found in
CC the liver and in the mesenchymal condensation sites of branchial
CC arches. {ECO:0000269|PubMed:8006062}.
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 -!- 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; X75603; CAA53271.1; -; mRNA.
DR PIR; S38579; S38579.
DR AlphaFoldDB; Q91287; -.
DR SMR; Q91287; -.
DR GlyCosmos; Q91287; 7 sites, No reported glycans.
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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:InterPro.
DR CDD; cd00096; Ig; 1.
DR CDD; cd05100; PTKc_FGFR3; 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:SF505; FIBROBLAST GROWTH FACTOR RECEPTOR 3; 1.
DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF13927; Ig_3; 1.
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 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Cell membrane; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..796
FT /note="Fibroblast growth factor receptor 3"
FT /id="PRO_0000249218"
FT TOPO_DOM 20..358
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 359..379
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 380..796
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..119
FT /note="Ig-like C2-type 1"
FT DOMAIN 140..233
FT /note="Ig-like C2-type 2"
FT DOMAIN 239..344
FT /note="Ig-like C2-type 3"
FT DOMAIN 457..746
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 117..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 602
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 463..471
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 493
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 632
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 633
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 709
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 745
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 304
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 56..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 165..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 264..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 796 AA; 88289 MW; 226D99A0B6D1D92D CRC64;
MLVWLCGLCL VTLAGGRSAA RLPLTEGRPT ADFLPGDASL VEELLFGTGD TIELSCTTPG
SSVSVVWFKD GISVDPPTWS HTGQKLLKII NVSYDDSGVY SCKARQSSEV LRNVTVRVTD
SPSSGDDEDD DEESESANAP KFTRPEWMEK KLLAVPAANT VRFRCPAAGK PTPSITWLKN
GKEFKGEHRI GGIKLRHQQW SLVMESVVPS DRGNYTCVVA NKYGTIRETY TLDVLERTPH
RPILQAGFRS NKTVVVGSDV EFHCKVYSDA QPHIQWLKHV EVNGSKFGPD GNPYVTVLKT
AGVNTSDKEL EIQFLRNVTF EDAGEYTCLA GNSIGYSHHS AWLTVLPPAE PVPDVDTSVS
ILAAAGCVAV VILVVIIIFT YKMKMPSKKT MNTATVHKVS KFPLKRQVSL ESNSSMNSNT
PLVRITRLSS SDGPMLANVS ELELPADPKW ELSRSRLTLG KPLGEGCFGQ VVMADAVGIE
KDKPNKATSV AVKMLKDDAT DKDLSDLVSE MEMMKMIGKH KNIINLLGAC TQDGPLYVLV
EYASKGNLRE YLRARRPPGM DYSFDTCKLP EEQLTFKDLV SCAYQVARGM EYLASQKCIH
RDLAARNVLV TDDNVMKIAD FGLARDVHNI DYYKKTTNGR LPVKWMAPEA LFDRVYTHQS
DVWSFGVLLW EIFTLGGSPY PGIPVEELFK LLKEGHRMDK PANCTHELYM IMRECWHAVP
SQRPTFKQLV EDLDRVLTVT STDEYLDLSV PFEQYSPACP DSHSSCSSGD DSVFAHDLPE
EPCLPKHQQY NGVIRT
//
