FGFR3_XENLA
ID FGFR3_XENLA Reviewed; 802 AA.
AC O42127;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Fibroblast growth factor receptor 3;
DE Short=FGFR-3;
DE EC=2.7.10.1;
DE Flags: Precursor;
GN Name=fgfr3;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10642793; DOI=10.1006/dbio.1999.9515;
RA Hongo I., Kengaku M., Okamoto H.;
RT "FGF signaling and the anterior neural induction in Xenopus.";
RL Dev. Biol. 216:561-581(1999).
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 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 -!- 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; AB007035; BAA22281.1; -; mRNA.
DR RefSeq; NP_001084170.1; NM_001090701.1.
DR AlphaFoldDB; O42127; -.
DR SMR; O42127; -.
DR GeneID; 399347; -.
DR KEGG; xla:399347; -.
DR CTD; 399347; -.
DR Xenbase; XB-GENE-17330101; fgfr3.S.
DR OrthoDB; 220433at2759; -.
DR Proteomes; UP000186698; Chromosome 1S.
DR Bgee; 399347; Expressed in zone of skin and 15 other tissues.
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; -; 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; 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; 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; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..?
FT /evidence="ECO:0000255"
FT CHAIN ?..802
FT /note="Fibroblast growth factor receptor 3"
FT /id="PRO_0000249206"
FT TOPO_DOM ?..362
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..802
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..115
FT /note="Ig-like C2-type 1"
FT DOMAIN 140..233
FT /note="Ig-like C2-type 2"
FT DOMAIN 242..342
FT /note="Ig-like C2-type 3"
FT DOMAIN 462..751
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 116..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..136
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 607
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 468..476
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 498
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 637
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 638
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 714
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 750
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
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 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 165..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 264..326
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 802 AA; 89516 MW; CC5E5DDF3BD25BD3 CRC64;
MVSVNGVPAA RLPVTLPGED RASRKAPDYL MVEQPPFDEL MYTIGETIEL SCAAEDASTT
TKWCKDGIGI VPNNRTSTRQ GLLKIINVSS DDSGIYSCRL WHSTEILRNF TIRVTDLPSS
GDDEDDDDDD DDETEDREPP RWTQPERMEK KLIAVPAANT IRFRCPAAGN PTPTIHWLKN
GKEFRGEHRI GGIKLRHQQW SLVMESVVPS DKGNYTCVVE NKYGSIRQTY QLDVLERSSH
RPILQAGLPG NQTVVLGSDV EFHCKVYSDA QPHIQWLKHV EVNGSKYGPD GDPYVSVLQS
FINGTEVDST LSLKNVTETN EGQYVCRANN FIGVAEASFW LHIYKPAPAE PVEKALTTSS
SSITVLIVVT STIVFILLVI IVITHLMKVP SKKSMTAPPV HKVSKFPLKR QQVSLESNSS
MNSNTPLVRI THLSSSDGTM LANVSELGLP LDPKWELLRS RLTLGKPLGE GCFGQVVMAE
AIGIDKERPN KPATVAVKML KDDATDKDLS DLVSEMEMMK MIGKHKNIIN LLGACTQDGP
LYVLVEYASK GSLREYLKAR RPPGMDYSFD ACKIPAEQLT FKDLVSCAYQ VARGMEYLAS
QKCIHRDLAA RNVLVTDDNV MKIADFGLAR DIHNIDYYKK TTNGRLPVKW MAPEALFDRI
YTHHSDVWSY GVLLWEIFTL GGSPYPGIPV EELFKLLKEG HRMDKPANCT HELYMIMREC
WHAVPSQRPA FKQLVEDLDR VLTVTSTNEY LDLSVAFEQY SPPSQDSHST CSSGDDSVFA
HDILPDEPCL PKHQQHNGAI PT
