FGFR3_DANRE
ID FGFR3_DANRE Reviewed; 800 AA.
AC Q9I8X3;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 132.
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 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], AND DEVELOPMENTAL STAGE.
RX PubMed=11287195; DOI=10.1016/s0925-4773(01)00280-5;
RA Sleptsova-Friedrich I., Li Y., Emelyanov A., Ekker M., Korzh V., Ge R.;
RT "fgfr3 and regionalization of anterior neural tube in zebrafish.";
RL Mech. Dev. 102:213-217(2001).
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 -!- 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 -!- DEVELOPMENTAL STAGE: Expression occurs in the axial mesoderm, the
CC diencephalon, the anterior hindbrain and the anterior spinal cord. In
CC the hindbrain, a differential expression was detected at several levels
CC of intensity, with the highest expression in the posterior rhombomere 1
CC that is morphologically distinct from the anterior part, which develops
CC into the cerebellum. {ECO:0000269|PubMed:11287195}.
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; AF157560; AAF80344.1; -; mRNA.
DR AlphaFoldDB; Q9I8X3; -.
DR SMR; Q9I8X3; -.
DR STRING; 7955.ENSDARP00000011898; -.
DR ZFIN; ZDB-GENE-000816-1; fgfr3.
DR InParanoid; Q9I8X3; -.
DR Reactome; R-DRE-109704; PI3K Cascade.
DR Reactome; R-DRE-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DRE-190371; FGFR3b ligand binding and activation.
DR Reactome; R-DRE-190372; FGFR3c ligand binding and activation.
DR Reactome; R-DRE-5654227; Phospholipase C-mediated cascade, FGFR3.
DR Reactome; R-DRE-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-DRE-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-DRE-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-DRE-5654732; Negative regulation of FGFR3 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; Q9I8X3; -.
DR PRO; PR:Q9I8X3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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; IBA:GO_Central.
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: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:0043410; P:positive regulation of MAPK cascade; 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 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 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.
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..20
FT /evidence="ECO:0000255"
FT CHAIN 21..800
FT /note="Fibroblast growth factor receptor 3"
FT /id="PRO_0000249205"
FT TOPO_DOM 21..363
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 364..384
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 385..800
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..122
FT /note="Ig-like C2-type 1"
FT DOMAIN 144..237
FT /note="Ig-like C2-type 2"
FT DOMAIN 246..348
FT /note="Ig-like C2-type 3"
FT DOMAIN 460..739
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 124..143
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..800
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 124..138
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 778..792
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 605
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 466..474
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 496
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 635
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 636
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 712
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 748
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 77
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 55..101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 169..221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 268..332
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 800 AA; 89716 MW; 8092DC0272A5BAD1 CRC64;
MVPLCLLLYL ATLVFPPVYS AHLLSPEPTD WVSSEVEVFL EDYVAGVGDT VVLSCTPQDF
LLPIVWQKDG DAVSSSNRTR VGQKALRIIN VSYEDSGVYS CRHAHKSMLL SNYTVKVIDS
LSSGDDEDYD EDEDEAGNGN AEAPYWTRSD RMEKKLLAVP AANTVKFRCP AAGNPTPSIH
WLKNGKEFKG EQRMGGIKLR HQQWSLVMES AVPSDRGNYT CVVQNKYGSI KHTYQLDVLE
RSPHRPILQA GLPANQTVVV GSDVEFHCKV YSDAQPHIQW LKHIEVNGSQ YGPNGAPYVN
VLKTAGINTT DKELEILYLT NVSFEDAGQY TCLAGNSIGY NHHSAWLTVL PAVEMEREDD
YADILIYVTS CVLFILTMVI IILCRMWINT QKTLPAPPVQ KLSKFPLKRQ VSLESNSSMN
SNTPLVRIAR LSSSDGPMLP NVSELELPSD PKWEFTRTKL TLGKPLGEGC FGQVVMAEAI
GIDKEKPNKP LTVAVKMLKD DGTDKDLSDL VSEMEMMKMI GKHKNIINLL GACTQDGPLY
VLVEYASKGN LREYLRARRP PGMDYSFDTC KIPNETLTFK DLVSCAYQVA RGMEYLASKK
CIHRDPAARN VLVTEDNVMK IADFGLARDV HNIDYYKKTT NGRLPVKWMA PEALFDRVYT
HQSDVWSYGV LLWEIFTLGG SPYPGIPVEE LFKLLKEGHR MDKPANCTHE LYMIMRECWH
AVPSQRPTFR QLVEDHDRVL SMTSTDEYLD LSVPFEQYSP TCPDSNSTCS SGDDSVFAHD
PLPEEPCLPK HHHSNGVIRT
