UniProtKB - P21802 (FGFR2_HUMAN)
Protein
Fibroblast growth factor receptor 2
Gene
FGFR2
Organism
Homo sapiens (Human)
Status
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, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.13 Publications
Catalytic activityi
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]PROSITE-ProRule annotation4 PublicationsEC:2.7.10.1PROSITE-ProRule annotation4 Publications
Activity regulationi
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by ARQ 523 and ARQ 069; these compounds maintain the kinase in an inactive conformation and inhibit autophosphorylation.2 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Binding sitei | 517 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
| Binding sitei | 571 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
| Active sitei | 626 | Proton acceptorPROSITE-ProRule annotation1 Publication | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Nucleotide bindingi | 487 – 495 | ATPPROSITE-ProRule annotation1 Publication | 9 | |
| Nucleotide bindingi | 565 – 567 | ATPPROSITE-ProRule annotation1 Publication | 3 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- fibroblast growth factor-activated receptor activity Source: UniProtKB
- fibroblast growth factor binding Source: UniProtKB
- heparin binding Source: UniProtKB-KW
- identical protein binding Source: IntAct
- protein homodimerization activity Source: UniProtKB
- protein tyrosine kinase activity Source: UniProtKB
- transmembrane receptor protein tyrosine kinase activity Source: GO_Central
GO - Biological processi
- angiogenesis Source: UniProtKB
- animal organ morphogenesis Source: UniProtKB
- apoptotic process Source: UniProtKB-KW
- axonogenesis Source: UniProtKB
- bone development Source: UniProtKB
- bone mineralization Source: UniProtKB
- bone morphogenesis Source: UniProtKB
- branch elongation involved in salivary gland morphogenesis Source: UniProtKB
- branching involved in labyrinthine layer morphogenesis Source: UniProtKB
- branching involved in prostate gland morphogenesis Source: UniProtKB
- branching involved in salivary gland morphogenesis Source: UniProtKB
- branching morphogenesis of a nerve Source: UniProtKB
- bud elongation involved in lung branching Source: UniProtKB
- cell-cell signaling Source: UniProtKB
- cell fate commitment Source: UniProtKB
- cellular response to retinoic acid Source: Ensembl
- cellular response to transforming growth factor beta stimulus Source: Ensembl
- digestive tract development Source: UniProtKB
- embryonic cranial skeleton morphogenesis Source: BHF-UCL
- embryonic digestive tract morphogenesis Source: UniProtKB
- embryonic organ development Source: UniProtKB
- embryonic organ morphogenesis Source: UniProtKB
- embryonic pattern specification Source: UniProtKB
- endochondral bone growth Source: Ensembl
- epidermis morphogenesis Source: UniProtKB
- epithelial cell differentiation Source: UniProtKB
- epithelial cell proliferation involved in salivary gland morphogenesis Source: UniProtKB
- epithelial to mesenchymal transition Source: Ensembl
- fibroblast growth factor receptor signaling pathway Source: UniProtKB
- fibroblast growth factor receptor signaling pathway involved in hemopoiesis Source: UniProtKB
- fibroblast growth factor receptor signaling pathway involved in mammary gland specification Source: UniProtKB
- fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell Source: UniProtKB
- fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development Source: UniProtKB
- fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow Source: UniProtKB
- gland morphogenesis Source: UniProtKB
- hair follicle morphogenesis Source: UniProtKB
- inner ear morphogenesis Source: UniProtKB
- in utero embryonic development Source: UniProtKB
- lacrimal gland development Source: UniProtKB
- lateral sprouting from an epithelium Source: UniProtKB
- limb bud formation Source: UniProtKB
- lung alveolus development Source: UniProtKB
- lung-associated mesenchyme development Source: UniProtKB
- lung development Source: UniProtKB
- lung lobe morphogenesis Source: UniProtKB
- mammary gland bud formation Source: UniProtKB
- MAPK cascade Source: Reactome
- membranous septum morphogenesis Source: UniProtKB
- mesenchymal cell differentiation Source: UniProtKB
- mesenchymal cell differentiation involved in lung development Source: UniProtKB
- mesenchymal cell proliferation involved in lung development Source: UniProtKB
- mesodermal cell differentiation Source: Ensembl
- midbrain development Source: UniProtKB
- morphogenesis of embryonic epithelium Source: UniProtKB
- multicellular organism development Source: GO_Central
- negative regulation of epithelial cell proliferation Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- odontogenesis Source: UniProtKB
- orbitofrontal cortex development Source: UniProtKB
- organ growth Source: UniProtKB
- otic vesicle formation Source: UniProtKB
- outflow tract septum morphogenesis Source: UniProtKB
- peptidyl-tyrosine phosphorylation Source: UniProtKB
- positive regulation of canonical Wnt signaling pathway Source: UniProtKB
- positive regulation of cardiac muscle cell proliferation Source: UniProtKB
- positive regulation of cell cycle Source: UniProtKB
- positive regulation of cell division Source: UniProtKB
- positive regulation of cell population proliferation Source: UniProtKB
- positive regulation of epithelial cell proliferation Source: UniProtKB
- positive regulation of epithelial cell proliferation involved in lung morphogenesis Source: UniProtKB
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of kinase activity Source: GO_Central
- positive regulation of MAPK cascade Source: UniProtKB
- positive regulation of mesenchymal cell proliferation Source: UniProtKB
- positive regulation of phospholipase activity Source: UniProtKB
- positive regulation of protein kinase B signaling Source: Reactome
- positive regulation of smooth muscle cell proliferation Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of Wnt signaling pathway Source: UniProtKB
- post-embryonic development Source: UniProtKB
- prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis Source: UniProtKB
- prostate epithelial cord elongation Source: UniProtKB
- prostate gland morphogenesis Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- pyramidal neuron development Source: UniProtKB
- regulation of ERK1 and ERK2 cascade Source: UniProtKB
- regulation of morphogenesis of a branching structure Source: UniProtKB
- regulation of osteoblast differentiation Source: UniProtKB
- regulation of osteoblast proliferation Source: UniProtKB
- regulation of smoothened signaling pathway Source: UniProtKB
- regulation of smooth muscle cell differentiation Source: UniProtKB
- reproductive structure development Source: UniProtKB
- response to ethanol Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- skeletal system morphogenesis Source: UniProtKB
- squamous basal epithelial stem cell differentiation involved in prostate gland acinus development Source: UniProtKB
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
- ureteric bud development Source: UniProtKB
- ventricular cardiac muscle tissue morphogenesis Source: UniProtKB
- ventricular zone neuroblast division Source: UniProtKB
- wound healing Source: Ensembl
Keywordsi
| Molecular function | Heparin-binding, Kinase, Receptor, Transferase, Tyrosine-protein kinase |
| Biological process | Apoptosis |
| Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
| BRENDAi | 2.7.10.1 2681 |
| Reactomei | R-HSA-109704 PI3K Cascade R-HSA-1257604 PIP3 activates AKT signaling R-HSA-190375 FGFR2c ligand binding and activation R-HSA-190377 FGFR2b ligand binding and activation R-HSA-2023837 Signaling by FGFR2 amplification mutants [P21802-17] R-HSA-2033519 Activated point mutants of FGFR2 R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-5654221 Phospholipase C-mediated cascade, FGFR2 R-HSA-5654695 PI-3K cascade:FGFR2 R-HSA-5654699 SHC-mediated cascade:FGFR2 R-HSA-5654700 FRS-mediated FGFR2 signaling R-HSA-5654727 Negative regulation of FGFR2 signaling R-HSA-5655253 Signaling by FGFR2 in disease R-HSA-5673001 RAF/MAP kinase cascade R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-8851708 Signaling by FGFR2 IIIa TM R-HSA-8853333 Signaling by FGFR2 fusions |
| SignaLinki | P21802 |
| SIGNORi | P21802 |
Names & Taxonomyi
| Protein namesi | Recommended name: Fibroblast growth factor receptor 2 (EC:2.7.10.14 Publications)Short name: FGFR-2 Alternative name(s): K-sam Short name: KGFR Keratinocyte growth factor receptor CD_antigen: CD332 |
| Gene namesi | Name:FGFR2 Synonyms:BEK, KGFR, KSAM |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:3689 FGFR2 |
| MIMi | 176943 gene |
| neXtProti | NX_P21802 |
Subcellular locationi
Golgi apparatus
Plasma membrane
Other locations
Note: Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded.
Plasma membrane
Note: After ligand binding, the activated receptor is rapidly internalized and degraded.
Plasma membrane
Note: After ligand binding, the activated receptor is rapidly internalized and degraded.
Extracellular region or secreted
Extracellular region or secreted
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: UniProtKB-SubCell
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: Reactome
Other locations
- cell cortex Source: UniProtKB
- cell surface Source: UniProtKB
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle Source: UniProtKB-KW
- excitatory synapse Source: UniProtKB
- integral component of membrane Source: UniProtKB
- membrane Source: UniProtKB
- receptor complex Source: GO_Central
Topology
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Topological domaini | 22 – 377 | ExtracellularSequence analysisAdd BLAST | 356 | |
| Transmembranei | 378 – 398 | HelicalSequence analysisAdd BLAST | 21 | |
| Topological domaini | 399 – 821 | CytoplasmicSequence analysisAdd BLAST | 423 |
Keywords - Cellular componenti
Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Crouzon syndrome (CS)17 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_004112 | 105 | Y → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs1434545235EnsemblClinVar. | 1 | |
| Natural variantiVAR_017261 | 263 | P → L in CS. 1 PublicationCorresponds to variant dbSNP:rs779326224Ensembl. | 1 | |
| Natural variantiVAR_004118 | 267 | S → P in CS. 1 PublicationCorresponds to variant dbSNP:rs121918505EnsemblClinVar. | 1 | |
| Natural variantiVAR_004119 | 268 | T → TG in CS. 1 Publication | 1 | |
| Natural variantiVAR_004120 | 276 | F → V in CS. 3 PublicationsCorresponds to variant dbSNP:rs1057519036EnsemblClinVar. | 1 | |
| Natural variantiVAR_004121 | 278 | C → F in CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. 5 PublicationsCorresponds to variant dbSNP:rs776587763EnsemblClinVar. | 1 | |
| Natural variantiVAR_017263 | 278 | C → Y in CS. 1 PublicationCorresponds to variant dbSNP:rs776587763EnsemblClinVar. | 1 | |
| Natural variantiVAR_017264 | 281 | Y → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs1057519038EnsemblClinVar. | 1 | |
| Natural variantiVAR_004122 | 287 – 289 | Missing in CS. | 3 | |
| Natural variantiVAR_017265 | 288 | I → S in CS. 1 Publication | 1 | |
| Natural variantiVAR_004123 | 289 | Q → P in CS and JWS. 5 PublicationsCorresponds to variant dbSNP:rs121918497EnsemblClinVar. | 1 | |
| Natural variantiVAR_017266 | 290 | W → G in CS. 1 PublicationCorresponds to variant dbSNP:rs121918501EnsemblClinVar. | 1 | |
| Natural variantiVAR_004125 | 290 | W → R in CS. Corresponds to variant dbSNP:rs121918501EnsemblClinVar. | 1 | |
| Natural variantiVAR_004126 | 292 | K → E in CS. 1 PublicationCorresponds to variant dbSNP:rs121918500EnsemblClinVar. | 1 | |
| Natural variantiVAR_004127 | 301 | Y → C in CS. 1 PublicationCorresponds to variant dbSNP:rs1554930684EnsemblClinVar. | 1 | |
| Natural variantiVAR_004130 | 328 | Y → C in CS. 1 PublicationCorresponds to variant dbSNP:rs121918493Ensembl. | 1 | |
| Natural variantiVAR_004131 | 331 | N → I in CS. 1 Publication | 1 | |
| Natural variantiVAR_004132 | 337 | A → ANA in CS. | 1 | |
| Natural variantiVAR_017268 | 337 | A → P in CS. 1 PublicationCorresponds to variant dbSNP:rs387906676Ensembl. | 1 | |
| Natural variantiVAR_004133 | 338 | G → E in CS. 1 PublicationCorresponds to variant dbSNP:rs1057519044Ensembl. | 1 | |
| Natural variantiVAR_015011 | 338 | G → R in CS. 3 PublicationsCorresponds to variant dbSNP:rs1057519043Ensembl. | 1 | |
| Natural variantiVAR_004134 | 340 | Y → H in CS. 2 PublicationsCorresponds to variant dbSNP:rs121918489Ensembl. | 1 | |
| Natural variantiVAR_004135 | 341 | T → P in PS and CS. 3 PublicationsCorresponds to variant dbSNP:rs121918495Ensembl. | 1 | |
| Natural variantiVAR_004136 | 342 | C → F in CS. 3 PublicationsCorresponds to variant dbSNP:rs121918487Ensembl. | 1 | |
| Natural variantiVAR_004137 | 342 | C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant dbSNP:rs121918488Ensembl. | 1 | |
| Natural variantiVAR_004138 | 342 | C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant dbSNP:rs121918488Ensembl. | 1 | |
| Natural variantiVAR_017271 | 342 | C → W in CS. 3 PublicationsCorresponds to variant dbSNP:rs121918496Ensembl. | 1 | |
| Natural variantiVAR_004139 | 342 | C → Y in CS and PS. 8 PublicationsCorresponds to variant dbSNP:rs121918487Ensembl. | 1 | |
| Natural variantiVAR_004140 | 344 | A → G in CS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121918492Ensembl. | 1 | |
| Natural variantiVAR_004141 | 344 | A → P in CS and PS. 1 Publication | 1 | |
| Natural variantiVAR_004142 | 347 | S → C in CS. 2 PublicationsCorresponds to variant dbSNP:rs121918494Ensembl. | 1 | |
| Natural variantiVAR_004143 | 351 | S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant dbSNP:rs121918502Ensembl. | 1 | |
| Natural variantiVAR_004144 | 354 | S → C in CS. 5 PublicationsCorresponds to variant dbSNP:rs121918490Ensembl. | 1 | |
| Natural variantiVAR_017272 | 354 | S → Y in CS. 1 Publication | 1 | |
| Natural variantiVAR_004145 | 356 – 358 | Missing in CS. 1 Publication | 3 | |
| Natural variantiVAR_004146 | 359 | V → F in CS and PS. 2 Publications | 1 | |
| Natural variantiVAR_017273 | 362 | A → S in CS. 1 Publication | 1 | |
| Natural variantiVAR_004147 | 384 | G → R in CS. 1 PublicationCorresponds to variant dbSNP:rs1554927408Ensembl. | 1 | |
| Natural variantiVAR_017276 | 549 | N → H in CS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs1057519045Ensembl. | 1 | |
| Natural variantiVAR_017281 | 678 | R → G in CS. 1 Publication | 1 |
Jackson-Weiss syndrome (JWS)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_004123 | 289 | Q → P in CS and JWS. 5 PublicationsCorresponds to variant dbSNP:rs121918497EnsemblClinVar. | 1 | |
| Natural variantiVAR_004140 | 344 | A → G in CS and JWS. 2 PublicationsCorresponds to variant dbSNP:rs121918492Ensembl. | 1 |
Apert syndrome (APRS)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_004114 | 252 | S → F in APRS; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs121918498EnsemblClinVar. | 1 | |
| Natural variantiVAR_004115 | 252 | S → W in APRS and PS; common mutation. 7 PublicationsCorresponds to variant dbSNP:rs79184941EnsemblClinVar. | 1 | |
| Natural variantiVAR_004117 | 253 | P → R in APRS; common mutation. 5 PublicationsCorresponds to variant dbSNP:rs77543610EnsemblClinVar. | 1 |
Pfeiffer syndrome (PS)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by the association of craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly of the fingers and toes. Three subtypes are known: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_017259 | 172 | A → F in PS; requires 2 nucleotide substitutions. 1 Publication | 1 | |
| Natural variantiVAR_004116 | 252 – 253 | SP → FS in PS. Corresponds to variant dbSNP:rs281865420Ensembl. | 2 | |
| Natural variantiVAR_004115 | 252 | S → W in APRS and PS; common mutation. 7 PublicationsCorresponds to variant dbSNP:rs79184941EnsemblClinVar. | 1 | |
| Natural variantiVAR_017262 | 273 | Missing in PS; type 2. 1 Publication | 1 | |
| Natural variantiVAR_004121 | 278 | C → F in CS, JWS and PS; forms disulfide-linked dimers with constitutive kinase activity, is retained in an intracellular compartment and not detected at the cell surface. 5 PublicationsCorresponds to variant dbSNP:rs776587763EnsemblClinVar. | 1 | |
| Natural variantiVAR_004124 | 290 | W → C in PS; severe; also in a lung squamous cell carcinoma sample; somatic mutation. 3 PublicationsCorresponds to variant dbSNP:rs121918499EnsemblClinVar. | 1 | |
| Natural variantiVAR_004129 | 321 | D → A in PS. 1 PublicationCorresponds to variant dbSNP:rs121918510Ensembl. | 1 | |
| Natural variantiVAR_017269 | 340 | Y → C in PS. 2 PublicationsCorresponds to variant dbSNP:rs1554928884Ensembl. | 1 | |
| Natural variantiVAR_004135 | 341 | T → P in PS and CS. 3 PublicationsCorresponds to variant dbSNP:rs121918495Ensembl. | 1 | |
| Natural variantiVAR_017270 | 342 | C → G in PS. 1 PublicationCorresponds to variant dbSNP:rs121918488Ensembl. | 1 | |
| Natural variantiVAR_004139 | 342 | C → Y in CS and PS. 8 PublicationsCorresponds to variant dbSNP:rs121918487Ensembl. | 1 | |
| Natural variantiVAR_004141 | 344 | A → P in CS and PS. 1 Publication | 1 | |
| Natural variantiVAR_004146 | 359 | V → F in CS and PS. 2 Publications | 1 | |
| Natural variantiVAR_017275 | 375 | Y → C in PS and BSTVS. 3 PublicationsCorresponds to variant dbSNP:rs121913478Ensembl. | 1 | |
| Natural variantiVAR_017277 | 565 | E → G in PS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918506Ensembl. | 1 | |
| Natural variantiVAR_017278 | 641 | K → R in PS; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs1057519047Ensembl. | 1 | |
| Natural variantiVAR_017280 | 663 | G → E in PS. 1 Publication | 1 |
Beare-Stevenson cutis gyrata syndrome (BSTVS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease characterized by craniofacial anomalies, particularly craniosynostosis, and ear defects, cutis gyrata, acanthosis nigricans, anogenital anomalies, skin tags, and prominent umbilical stump. The skin furrows have a corrugated appearance and are widespread. Cutis gyrata variably affects the scalp, forehead, face, preauricular area, neck, trunk, hands, and feet.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_017274 | 372 | S → C in BSTVS. 1 PublicationCorresponds to variant dbSNP:rs121913477Ensembl. | 1 | |
| Natural variantiVAR_017275 | 375 | Y → C in PS and BSTVS. 3 PublicationsCorresponds to variant dbSNP:rs121913478Ensembl. | 1 |
Familial scaphocephaly syndrome (FSPC)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_023788 | 526 | K → E in FSPC; constitutive kinase activity. 2 PublicationsCorresponds to variant dbSNP:rs121918507Ensembl. | 1 |
Lacrimo-auriculo-dento-digital syndrome (LADDS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Lacrimo-auriculo-dento-digital syndrome is characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_029884 | 628 | A → T in LADDS; strongly reduced kinase activity. 1 PublicationCorresponds to variant dbSNP:rs121918509Ensembl. | 1 | |
| Natural variantiVAR_029885 | 648 | A → T in LADDS. 1 PublicationCorresponds to variant dbSNP:rs121918508Ensembl. | 1 | |
| Natural variantiVAR_029886 | 649 – 650 | RD → S in LADDS. 1 Publication | 2 |
Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis (ABS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_004137 | 342 | C → R in CS, JWS, PS and ABS2. 9 PublicationsCorresponds to variant dbSNP:rs121918488Ensembl. | 1 | |
| Natural variantiVAR_004138 | 342 | C → S in CS, JWS, PS and ABS2. 8 PublicationsCorresponds to variant dbSNP:rs121918488Ensembl. | 1 | |
| Natural variantiVAR_004143 | 351 | S → C in CS, PS and ABS2. 3 PublicationsCorresponds to variant dbSNP:rs121918502Ensembl. | 1 |
Bent bone dysplasia syndrome (BBDS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_067977 | 381 | Y → D in BBDS. 1 PublicationCorresponds to variant dbSNP:rs387906678Ensembl. | 1 | |
| Natural variantiVAR_067978 | 391 | M → R in BBDS; the mutation selectively reduces plasma-membrane levels of the protein and markedly diminishes the receptor's responsiveness to extracellular FGF. 1 PublicationCorresponds to variant dbSNP:rs387906677Ensembl. | 1 |
Saethre-Chotzen syndrome (SCS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_075856 | 269 – 270 | Missing in SCS. 1 Publication | 2 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 265 | N → Q: Reduced N-glycosylation. Reduced expression at the cell surface. 1 Publication | 1 | |
| Mutagenesisi | 549 | N → T: Constitutive kinase activity. 1 Publication | 1 | |
| Mutagenesisi | 565 | E → A: Constitutive kinase activity. 1 Publication | 1 | |
| Mutagenesisi | 656 – 657 | Missing : Loss of kinase activity. 1 Publication | 2 | |
| Mutagenesisi | 769 | Y → F: Increases fibroblast proliferation. Decreases phosphorylation of PLCG1 and FRS2. Decreases activation of MAP kinases. 2 Publications | 1 |
Keywords - Diseasei
Craniosynostosis, Disease mutation, Ectodermal dysplasia, Lacrimo-auriculo-dento-digital syndrome, Mental retardation, Proto-oncogeneOrganism-specific databases
| DisGeNETi | 2263 |
| GeneReviewsi | FGFR2 |
| MalaCardsi | FGFR2 |
| MIMi | 101200 phenotype 101400 phenotype 101600 phenotype 123150 phenotype 123500 phenotype 123790 phenotype 149730 phenotype 207410 phenotype 609579 phenotype 614592 phenotype |
| OpenTargetsi | ENSG00000066468 |
| Orphaneti | 83 Antley-Bixler syndrome 87 Apert syndrome 207 Crouzon disease 1555 Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome 168624 Familial scaphocephaly syndrome, McGillivray type 313855 FGFR2-related bent bone dysplasia 1540 Jackson-Weiss syndrome 2363 Lacrimoauriculodentodigital syndrome 93258 Pfeiffer syndrome type 1 93259 Pfeiffer syndrome type 2 93260 Pfeiffer syndrome type 3 794 Saethre-Chotzen syndrome |
| PharmGKBi | PA28128 |
Miscellaneous databases
| Pharosi | P21802 Tclin |
Chemistry databases
| ChEMBLi | CHEMBL4142 |
| DrugBanki | DB02058 3-[4-(1-formylpiperazin-4-yl)-benzylidenyl]-2-indolinone DB02491 4-[4-(1-Amino-1-Methylethyl)Phenyl]-5-Chloro-N-[4-(2-Morpholin-4-Ylethyl)Phenyl]Pyrimidin-2-Amine DB12147 Erdafitinib DB10770 Foreskin fibroblast (neonatal) DB10772 Foreskin keratinocyte (neonatal) DB12010 Fostamatinib DB01109 Heparin DB09078 Lenvatinib DB09079 Nintedanib DB00039 Palifermin DB08901 Ponatinib DB08896 Regorafenib DB01901 Sucrosofate DB01041 Thalidomide |
| DrugCentrali | P21802 |
| GuidetoPHARMACOLOGYi | 1809 |
Polymorphism and mutation databases
| BioMutai | FGFR2 |
| DMDMi | 120049 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
| ChainiPRO_0000016783 | 22 – 821 | Fibroblast growth factor receptor 2Add BLAST | 800 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Disulfide bondi | 62 ↔ 107 | PROSITE-ProRule annotation | ||
| Glycosylationi | 83 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 123 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 179 ↔ 231 | PROSITE-ProRule annotation1 Publication | ||
| Glycosylationi | 228 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 241 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 265 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Disulfide bondi | 278 ↔ 342 | PROSITE-ProRule annotation1 Publication | ||
| Glycosylationi | 297 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 318 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Glycosylationi | 331 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
| Modified residuei | 466 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
| Modified residuei | 586 | Phosphotyrosine; by autocatalysis3 Publications | 1 | |
| Modified residuei | 588 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
| Modified residuei | 656 | Phosphotyrosine; by autocatalysis3 Publications | 1 | |
| Modified residuei | 657 | Phosphotyrosine; by autocatalysis3 Publications | 1 | |
| Modified residuei | 769 | Phosphotyrosine; by autocatalysis2 Publications | 1 | |
| Modified residuei | 780 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on several tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Phosphorylation at Tyr-769 is essential for interaction with PLCG1.2 Publications
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.2 Publications
Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome.3 Publications
Keywords - PTMi
Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
| jPOSTi | P21802 |
| MassIVEi | P21802 |
| PaxDbi | P21802 |
| PeptideAtlasi | P21802 |
| PRIDEi | P21802 |
| ProteomicsDBi | 53905 [P21802-1] 53910 [P21802-14] 53911 [P21802-15] 53912 [P21802-16] 53913 [P21802-17] 53914 [P21802-18] 53915 [P21802-19] 53916 [P21802-2] 53917 [P21802-20] 53918 [P21802-21] 53919 [P21802-22] 53920 [P21802-23] 53921 [P21802-3] 53922 [P21802-4] 53923 [P21802-5] 53924 [P21802-6] 53926 [P21802-8] |
| TopDownProteomicsi | P21802-8 [P21802-8] |
PTM databases
| GlyConnecti | 1997 |
| iPTMneti | P21802 |
| PhosphoSitePlusi | P21802 |
Expressioni
Gene expression databases
| Bgeei | ENSG00000066468 Expressed in C1 segment of cervical spinal cord and 221 other tissues |
| ExpressionAtlasi | P21802 baseline and differential |
| Genevisiblei | P21802 HS |
Organism-specific databases
| HPAi | ENSG00000066468 Tissue enhanced (brain) |
Interactioni
Subunit structurei
Monomer. Homodimer after ligand binding.
Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Isoform 1 has high affinity for FGF1 and FGF2, but low affinity for FGF7. Isoform 3 has high affinity for FGF1 and FGF7, and has much higher affinity for FGF7 than isoform 1 (in vitro). 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 PLCG1, GRB2 and PAK4.
Interacts with FLRT2 (By similarity).
By similarity21 PublicationsBinary interactionsi
Show more detailsGO - Molecular functioni
- fibroblast growth factor binding Source: UniProtKB
- identical protein binding Source: IntAct
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
| BioGridi | 108554, 103 interactors |
| CORUMi | P21802 |
| DIPi | DIP-3788N |
| IntActi | P21802, 89 interactors |
| MINTi | P21802 |
| STRINGi | 9606.ENSP00000410294 |
Chemistry databases
| BindingDBi | P21802 |
Miscellaneous databases
| RNActi | P21802 protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details