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Protein

Fibroblast growth factor receptor 3

Gene

Fgfr3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tyrosine-protein kinase that acts as 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. Required for normal development of the inner ear. 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. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of STAT1, STAT5A and STAT5B. Plays a role in postnatal lung development.6 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei502ATPPROSITE-ProRule annotation1
Active sitei611Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi472 – 480ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • alveolar secondary septum development Source: MGI
  • axonogenesis involved in innervation Source: MGI
  • bone development Source: MGI
  • bone maturation Source: BHF-UCL
  • bone mineralization Source: BHF-UCL
  • bone morphogenesis Source: BHF-UCL
  • bone trabecula morphogenesis Source: MGI
  • cartilage development Source: MGI
  • cell differentiation Source: MGI
  • central nervous system myelination Source: MGI
  • cochlea development Source: MGI
  • digestive tract morphogenesis Source: MGI
  • epithelial cell fate commitment Source: MGI
  • ERK1 and ERK2 cascade Source: MGI
  • fibroblast growth factor receptor apoptotic signaling pathway Source: UniProtKB
  • fibroblast growth factor receptor signaling pathway Source: UniProtKB
  • forebrain development Source: MGI
  • inner ear development Source: MGI
  • inner ear receptor cell differentiation Source: MGI
  • lens fiber cell development Source: MGI
  • lens morphogenesis in camera-type eye Source: MGI
  • MAPK cascade Source: MGI
  • morphogenesis of an epithelium Source: MGI
  • negative regulation of astrocyte differentiation Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of developmental growth Source: BHF-UCL
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of gene expression Source: MGI
  • negative regulation of mitotic nuclear division Source: MGI
  • negative regulation of smoothened signaling pathway Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • oligodendrocyte development Source: MGI
  • p38MAPK cascade Source: MGI
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of bone mineralization Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: MGI
  • positive regulation of cell differentiation Source: ParkinsonsUK-UCL
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cell proliferation in bone marrow Source: MGI
  • positive regulation of endothelial cell proliferation Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of MAPK cascade Source: UniProtKB
  • positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway Source: MGI
  • positive regulation of neuron apoptotic process Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase activity Source: UniProtKB
  • positive regulation of phospholipase activity Source: UniProtKB
  • positive regulation of protein ubiquitination Source: MGI
  • positive regulation of tyrosine phosphorylation of Stat1 protein Source: UniProtKB
  • positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
  • post-anal tail morphogenesis Source: BHF-UCL
  • protein autophosphorylation Source: UniProtKB
  • regulation of bone remodeling Source: MGI
  • regulation of collagen metabolic process Source: MGI
  • regulation of ossification Source: MGI
  • regulation of osteoclast differentiation Source: MGI
  • response to axon injury Source: MGI
  • somatic stem cell population maintenance Source: MGI
  • substantia nigra development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor receptor 3 (EC:2.7.10.1)
Short name:
FGFR-3
Alternative name(s):
Heparin-binding growth factor receptor
CD_antigen: CD333
Gene namesi
Name:Fgfr3
Synonyms:Mfr3, Sam3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:95524. Fgfr3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 369ExtracellularSequence analysisAdd BLAST349
Transmembranei370 – 390HelicalSequence analysisAdd BLAST21
Topological domaini391 – 801CytoplasmicSequence analysisAdd BLAST411

GO - Cellular componenti

  • cytoplasmic side of plasma membrane Source: MGI
  • endoplasmic reticulum Source: MGI
  • Golgi apparatus Source: MGI
  • integral component of plasma membrane Source: UniProtKB
  • lysosome Source: MGI
  • perinuclear region of cytoplasm Source: MGI
  • plasma membrane Source: MGI
  • transport vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice exhibit defects in their skeleton, including kyphosis, scoliosis, crooked tails and curvature and overgrowth of long bones and vertebrae. This bone dysplasia is due to defects in the regulation of chondrocyte proliferation and differentiation in the cartilaginous growth plate. Mice also display inner ear defects including failure of pillar cell differentiation and tunnel of Corti formation, resulting in profound deafness. Mice lacking both FGFR3 and FGFR4 display pronounced dwarfism, and while their lungs appear normal at birth, they are completely blocked in alveogenesis and do not form secondary septae to delimit alveoli. These mice also show elevated serum levels of 1,25-dihydroxyvitamin D3 and reduced serum phosphorus levels.4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi644K → E: Constitutively activated kinase. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4066.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001678621 – 801Fibroblast growth factor receptor 3Add BLAST781

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi59 ↔ 107PROSITE-ProRule annotation
Glycosylationi96N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi170 ↔ 222PROSITE-ProRule annotation
Glycosylationi219N-linked (GlcNAc...)Sequence analysis1
Glycosylationi256N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi269 ↔ 333PROSITE-ProRule annotation
Glycosylationi288N-linked (GlcNAc...)Sequence analysis1
Glycosylationi309N-linked (GlcNAc...)Sequence analysis1
Glycosylationi322N-linked (GlcNAc...)Sequence analysis1
Modified residuei438PhosphoserineCombined sources1
Modified residuei439PhosphoserineCombined sources1
Modified residuei641Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei642Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei719Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei755Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

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. Phosphorylation at Tyr-719 is essential for stimulation of cell proliferation and activation of PIK3R1, STAT1 and MAP kinase signaling. Phosphorylation at Tyr-755 is required for interaction with PIK3R1 and PLCG1 (By similarity).By similarity
Ubiquitinated. Is rapidly ubiquitinated after ligand binding and autophosphorylation, leading to receptor internalization and degradation. Subject to both proteasomal and lysosomal degradation (By similarity).By similarity
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ61851.
PRIDEiQ61851.

PTM databases

iPTMnetiQ61851.
PhosphoSitePlusiQ61851.

Expressioni

Tissue specificityi

In embryo, expressed in heart, lung, kidney, skin, head and liver but not in muscle. In adult, highest levels in brain. Also expressed in liver, lung, kidney, testis, ovary and uterus. Very low levels in heart, thymus, spleen and muscle.

Developmental stagei

Expressed in embryos from mid-gestation and in adult.

Gene expression databases

CleanExiMM_FGFR3.

Interactioni

Subunit structurei

Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6; FGF8, FGF9, FGF10, FGF17, FGF18, FGF19, FGF20 and FGF23 (in vitro). Interacts with KLB. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PIK3R1, PLCG1, SOCS1 and SOCS3 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Sh2b2Q9JID93EBI-6287052,EBI-8100899

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-6031N.
IntActiQ61851. 2 interactors.
MINTiMINT-5181473.
STRINGi10090.ENSMUSP00000133064.

Chemistry databases

BindingDBiQ61851.

Structurei

3D structure databases

ProteinModelPortaliQ61851.
SMRiQ61851.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 124Ig-like C2-type 1Add BLAST103
Domaini145 – 238Ig-like C2-type 2Add BLAST94
Domaini247 – 349Ig-like C2-type 3Add BLAST103
Domaini466 – 756Protein kinasePROSITE-ProRule annotationAdd BLAST291

Domaini

The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.By similarity

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiQ61851.
PhylomeDBiQ61851.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q61851-1) [UniParc]FASTAAdd to basket
Also known as: IIIc

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVVPACVLVF CVAVVAGATS EPPGPEQRVV RRAAEVPGPE PSQQEQVAFG
60 70 80 90 100
SGDTVELSCH PPGGAPTGPT VWAKDGTGLV ASHRILVGPQ RLQVLNASHE
110 120 130 140 150
DAGVYSCQHR LTRRVLCHFS VRVTDAPSSG DDEDGEDVAE DTGAPYWTRP
160 170 180 190 200
ERMDKKLLAV PAANTVRFRC PAAGNPTPSI SWLKNGKEFR GEHRIGGIKL
210 220 230 240 250
RHQQWSLVME SVVPSDRGNY TCVVENKFGS IRQTYTLDVL ERSPHRPILQ
260 270 280 290 300
AGLPANQTAI LGSDVEFHCK VYSDAQPHIQ WLKHVEVNGS KVGPDGTPYV
310 320 330 340 350
TVLKTAGANT TDKELEVLSL HNVTFEDAGE YTCLAGNSIG FSHHSAWLVV
360 370 380 390 400
LPAEEELMET DEAGSVYAGV LSYGVVFFLF ILVVAAVILC RLRSPPKKGL
410 420 430 440 450
GSPTVHKVSR FPLKRQVSLE SNSSMNSNTP LVRIARLSSG EGPVLANVSE
460 470 480 490 500
LELPADPKWE LSRTRLTLGK PLGEGCFGQV VMAEAIGIDK DRTAKPVTVA
510 520 530 540 550
VKMLKDDATD KDLSDLVSEM EMMKMIGKHK NIINLLGACT QGGPLYVLVE
560 570 580 590 600
YAAKGNLREF LRARRPPGMD YSFDACRLPE EQLTCKDLVS CAYQVARGME
610 620 630 640 650
YLASQKCIHR DLAARNVLVT EDNVMKIADF GLARDVHNLD YYKKTTNGRL
660 670 680 690 700
PVKWMAPEAL FDRVYTHQSD VWSFGVLLWE IFTPGGPSPY PGIPVEELFK
710 720 730 740 750
LLKEGHRMDK PASCTHDLYM IMRECWHAVP SQRPTFKQLV EDLDRILTVT
760 770 780 790 800
STDEYLDLSV PFEQYSPGGQ DTPSSSSSGD DSVFTHDLLP PGPPSNGGPR

T
Length:801
Mass (Da):87,758
Last modified:November 1, 1996 - v1
Checksum:i68BC110212691705
GO
Isoform 2 (identifier: Q61851-2) [UniParc]FASTAAdd to basket
Also known as: IIIb

The sequence of this isoform differs from the canonical sequence as follows:
     305-352: TAGANTTDKE...HHSAWLVVLP → SWISENVEAD...FWLRVHGPQA

Show »
Length:803
Mass (Da):88,246
Checksum:iF45BCEDCB9795093
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti684P → L in AAB25535 (PubMed:8382556).Curated1
Sequence conflicti687Missing in AAB25535 (PubMed:8382556).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002990305 – 352TAGAN…LVVLP → SWISENVEADARLRLANVSE RDGGEYLCRATNFIGVAEKA FWLRVHGPQA in isoform 2. CuratedAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81342 mRNA. Translation: AAA39535.1.
S56291 mRNA. Translation: AAB25535.1.
L26492 Genomic DNA. Translation: AAA21490.2.
PIRiA48991.
I55363.
UniGeneiMm.6904.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81342 mRNA. Translation: AAA39535.1.
S56291 mRNA. Translation: AAB25535.1.
L26492 Genomic DNA. Translation: AAA21490.2.
PIRiA48991.
I55363.
UniGeneiMm.6904.

3D structure databases

ProteinModelPortaliQ61851.
SMRiQ61851.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-6031N.
IntActiQ61851. 2 interactors.
MINTiMINT-5181473.
STRINGi10090.ENSMUSP00000133064.

Chemistry databases

BindingDBiQ61851.
ChEMBLiCHEMBL4066.

PTM databases

iPTMnetiQ61851.
PhosphoSitePlusiQ61851.

Proteomic databases

PaxDbiQ61851.
PRIDEiQ61851.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:95524. Fgfr3.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000263410.
HOVERGENiHBG000345.
InParanoidiQ61851.
PhylomeDBiQ61851.

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Miscellaneous databases

ChiTaRSiFgfr3. mouse.
PROiQ61851.
SOURCEiSearch...

Gene expression databases

CleanExiMM_FGFR3.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
InterProiIPR016248. FGF_rcpt_fam.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07679. I-set. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF000628. FGFR. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00409. IG. 3 hits.
SM00408. IGc2. 3 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFGFR3_MOUSE
AccessioniPrimary (citable) accession number: Q61851
Secondary accession number(s): Q61564, Q63834
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.