Q91287 · FGFR3_PLEWA
- ProteinFibroblast growth factor receptor 3
- GeneFGFR3
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids796 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway (By similarity).
Catalytic activity
- L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
Activity regulation
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | plasma membrane | |
Cellular Component | receptor complex | |
Molecular Function | ATP binding | |
Molecular Function | fibroblast growth factor binding | |
Molecular Function | fibroblast growth factor receptor activity | |
Biological Process | apoptotic process | |
Biological Process | positive regulation of cell population proliferation | |
Biological Process | positive regulation of kinase activity | |
Biological Process | positive regulation of MAPK cascade | |
Biological Process | protein phosphorylation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFibroblast growth factor receptor 3
- EC number
- Short namesFGFR-3
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Caudata > Salamandroidea > Salamandridae > Pleurodelinae > Pleurodeles
Accessions
- Primary accessionQ91287
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 20-358 | Extracellular | ||||
Sequence: ARLPLTEGRPTADFLPGDASLVEELLFGTGDTIELSCTTPGSSVSVVWFKDGISVDPPTWSHTGQKLLKIINVSYDDSGVYSCKARQSSEVLRNVTVRVTDSPSSGDDEDDDEESESANAPKFTRPEWMEKKLLAVPAANTVRFRCPAAGKPTPSITWLKNGKEFKGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVANKYGTIRETYTLDVLERTPHRPILQAGFRSNKTVVVGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKFGPDGNPYVTVLKTAGVNTSDKELEIQFLRNVTFEDAGEYTCLAGNSIGYSHHSAWLTVLPPAEPVPDVDTS | ||||||
Transmembrane | 359-379 | Helical | ||||
Sequence: VSILAAAGCVAVVILVVIIIF | ||||||
Topological domain | 380-796 | Cytoplasmic | ||||
Sequence: TYKMKMPSKKTMNTATVHKVSKFPLKRQVSLESNSSMNSNTPLVRITRLSSSDGPMLANVSELELPADPKWELSRSRLTLGKPLGEGCFGQVVMADAVGIEKDKPNKATSVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVLVEYASKGNLREYLRARRPPGMDYSFDTCKLPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTDDNVMKIADFGLARDVHNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSVPFEQYSPACPDSHSSCSSGDDSVFAHDLPEEPCLPKHQQYNGVIRT |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-19 | |||||
Sequence: MLVWLCGLCLVTLAGGRSA | ||||||
Chain | PRO_0000249218 | 20-796 | Fibroblast growth factor receptor 3 | |||
Sequence: ARLPLTEGRPTADFLPGDASLVEELLFGTGDTIELSCTTPGSSVSVVWFKDGISVDPPTWSHTGQKLLKIINVSYDDSGVYSCKARQSSEVLRNVTVRVTDSPSSGDDEDDDEESESANAPKFTRPEWMEKKLLAVPAANTVRFRCPAAGKPTPSITWLKNGKEFKGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVANKYGTIRETYTLDVLERTPHRPILQAGFRSNKTVVVGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKFGPDGNPYVTVLKTAGVNTSDKELEIQFLRNVTFEDAGEYTCLAGNSIGYSHHSAWLTVLPPAEPVPDVDTSVSILAAAGCVAVVILVVIIIFTYKMKMPSKKTMNTATVHKVSKFPLKRQVSLESNSSMNSNTPLVRITRLSSSDGPMLANVSELELPADPKWELSRSRLTLGKPLGEGCFGQVVMADAVGIEKDKPNKATSVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVLVEYASKGNLREYLRARRPPGMDYSFDTCKLPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTDDNVMKIADFGLARDVHNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVLTVTSTDEYLDLSVPFEQYSPACPDSHSSCSSGDDSVFAHDLPEEPCLPKHQQYNGVIRT | ||||||
Disulfide bond | 56↔102 | |||||
Sequence: CTTPGSSVSVVWFKDGISVDPPTWSHTGQKLLKIINVSYDDSGVYSC | ||||||
Glycosylation | 91 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 113 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 165↔217 | |||||
Sequence: CPAAGKPTPSITWLKNGKEFKGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTC | ||||||
Glycosylation | 214 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 251 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 264↔328 | |||||
Sequence: CKVYSDAQPHIQWLKHVEVNGSKFGPDGNPYVTVLKTAGVNTSDKELEIQFLRNVTFEDAGEYTC | ||||||
Glycosylation | 283 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 304 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 317 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 632 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 633 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 709 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 745 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y |
Post-translational modification
Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer (By similarity).
Keywords
- PTM
PTM databases
Expression
Tissue specificity
Undetectable in the adult skeletal muscle. Low levels of expression were detected in the liver, lung and kidney. Medium levels of expression were detected in the heart, spleen, intestine and eye. Highest expression is observed in the testis.
Developmental stage
Maternally transcript whose a low level of expression persists during the cleavage and gastrula stages and a significant increase was observed at the end of the gastrula stage. Mainly localized to the ectoderm at the early gastrula stage and then shifted to the embryonic neural tissues, whereas adult brain had decreased levels of expression. Strong expression in the germinal epithelium of the embryonic brain (especially the diencephalon and rhombencephalon) and neural tube, in the lens and the cranial ganglia. The epithelium of the developing gut, like the pharynx and esophagus, also prominently expressed it. Other sites of expression were found in the liver and in the mesenchymal condensation sites of branchial arches.
Interaction
Subunit
Monomer. Homodimer after ligand binding (By similarity).
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 21-119 | Ig-like C2-type 1 | ||||
Sequence: RLPLTEGRPTADFLPGDASLVEELLFGTGDTIELSCTTPGSSVSVVWFKDGISVDPPTWSHTGQKLLKIINVSYDDSGVYSCKARQSSEVLRNVTVRVT | ||||||
Region | 117-142 | Disordered | ||||
Sequence: RVTDSPSSGDDEDDDEESESANAPKF | ||||||
Domain | 140-233 | Ig-like C2-type 2 | ||||
Sequence: PKFTRPEWMEKKLLAVPAANTVRFRCPAAGKPTPSITWLKNGKEFKGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVANKYGTIRETYTLD | ||||||
Domain | 239-344 | Ig-like C2-type 3 | ||||
Sequence: PHRPILQAGFRSNKTVVVGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKFGPDGNPYVTVLKTAGVNTSDKELEIQFLRNVTFEDAGEYTCLAGNSIGYSHHSAWLT | ||||||
Domain | 457-746 | Protein kinase | ||||
Sequence: LTLGKPLGEGCFGQVVMADAVGIEKDKPNKATSVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVLVEYASKGNLREYLRARRPPGMDYSFDTCKLPEEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTDDNVMKIADFGLARDVHNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRVLTVTSTDEYL |
Domain
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
Sequence similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length796
- Mass (Da)88,289
- Last updated1996-11-01 v1
- Checksum226D99A0B6D1D92D