Names & Taxonomy
- Uniprot ID:
- P21802
- Entry Name:
- FGFR2_HUMAN
- Status:
- reviewed
- Protein Names:
- Fibroblast growth factor receptor 2 (FGFR-2) (EC 2.7.10.1) (K-sam) (KGFR) (Keratinocyte growth factor receptor) (CD antigen CD332)
- Gene Names:
- FGFR2 BEK KGFR KSAM
- Gene Names Primary:
- FGFR2
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 821
- Sequence:
- MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGESLEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane; Single-pass type I membrane protein. Golgi apparatus. Cytoplasmic vesicle. Note=Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded.; Isoform 1: Cell membrane; Single-pass type I membrane protein. Note=After ligand binding, the activated receptor is rapidly internalized and degraded.; Isoform 3: Cell membrane; Single-pass type I membrane protein. Note=After ligand binding, the activated receptor is rapidly internalized and degraded.; Isoform 14: Secreted.; Isoform 19: Secreted.
Function
- Function:
- 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.
- Catalytic Activity:
- ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
- Enzyme Regulation:
- ENZYME REGULATION: 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.
- Active Site:
- ACT_SITE 626 626 Proton acceptor.
- Cross Reference Drug Bank:
- DB09078 DB09079 DB00039 DB08901 DB08896 DB01041
- Gene Ontology Go:
- cell cortex
cell surface
cytoplasm
cytoplasmic, membrane-bounded vesicle
excitatory synapse
extracellular region
Golgi apparatus
integral component of membrane
integral component of plasma membrane
intracellular membrane-bounded organelle
membrane
nucleoplasm
nucleus
plasma membrane
ATP binding
fibroblast growth factor binding
fibroblast growth factor-activated receptor activity
heparin binding
protein homodimerization activity
protein tyrosine kinase activity
activation of MAPKK activity
angiogenesis
apoptotic process
axon guidance
axonogenesis
bone development
bone mineralization
bone morphogenesis
branch elongation involved in salivary gland morphogenesis
branching involved in labyrinthine layer morphogenesis
branching involved in prostate gland morphogenesis
branching involved in salivary gland morphogenesis
branching morphogenesis of a nerve
bud elongation involved in lung branching
cell fate commitment
cell-cell signaling
digestive tract development
embryonic cranial skeleton morphogenesis
embryonic digestive tract morphogenesis
embryonic organ development
embryonic organ morphogenesis
embryonic pattern specification
epidermal growth factor receptor signaling pathway
epidermis morphogenesis
epithelial cell differentiation
epithelial cell proliferation involved in salivary gland morphogenesis
epithelial to mesenchymal transition
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway involved in hemopoiesis
fibroblast growth factor receptor signaling pathway involved in mammary gland specification
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow
gland morphogenesis
hair follicle morphogenesis
in utero embryonic development
innate immune response
inner ear morphogenesis
insulin receptor signaling pathway
lacrimal gland development
lateral sprouting from an epithelium
limb bud formation
lung alveolus development
lung development
lung lobe morphogenesis
lung-associated mesenchyme development
mammary gland bud formation
MAPK cascade
membranous septum morphogenesis
mesenchymal cell differentiation
mesenchymal cell differentiation involved in lung development
mesenchymal cell proliferation involved in lung development
mesodermal cell differentiation
midbrain development
morphogenesis of embryonic epithelium
multicellular organism growth
negative regulation of epithelial cell proliferation
negative regulation of transcription from RNA polymerase II promoter
neurotrophin TRK receptor signaling pathway
odontogenesis
orbitofrontal cortex development
organ growth
organ morphogenesis
otic vesicle formation
outflow tract septum morphogenesis
peptidyl-tyrosine phosphorylation
phosphatidylinositol-mediated signaling
positive regulation of canonical Wnt signaling pathway
positive regulation of cardiac muscle cell proliferation
positive regulation of cell cycle
positive regulation of cell division
positive regulation of cell proliferation
positive regulation of epithelial cell proliferation
positive regulation of epithelial cell proliferation involved in lung morphogenesis
positive regulation of ERK1 and ERK2 cascade
positive regulation of MAPK cascade
positive regulation of mesenchymal cell proliferation
positive regulation of phospholipase activity
positive regulation of smooth muscle cell proliferation
positive regulation of transcription from RNA polymerase II promoter
positive regulation of Wnt signaling pathway
post-embryonic development
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
prostate epithelial cord elongation
prostate gland morphogenesis
protein autophosphorylation
pyramidal neuron development
Ras protein signal transduction
regulation of branching involved in prostate gland morphogenesis
regulation of cell fate commitment
regulation of ERK1 and ERK2 cascade
regulation of fibroblast growth factor receptor signaling pathway
regulation of morphogenesis of a branching structure
regulation of multicellular organism growth
regulation of osteoblast differentiation
regulation of osteoblast proliferation
regulation of smooth muscle cell differentiation
regulation of smoothened signaling pathway
reproductive structure development
skeletal system morphogenesis
small GTPase mediated signal transduction
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development
ureteric bud development
vascular endothelial growth factor receptor signaling pathway
ventricular cardiac muscle tissue morphogenesis
ventricular zone neuroblast division - Gene Ontology Biological Process:
- activation of MAPKK activity
angiogenesis
apoptotic process
axon guidance
axonogenesis
bone development
bone mineralization
bone morphogenesis
branch elongation involved in salivary gland morphogenesis
branching involved in labyrinthine layer morphogenesis
branching involved in prostate gland morphogenesis
branching involved in salivary gland morphogenesis
branching morphogenesis of a nerve
bud elongation involved in lung branching
cell-cell signaling
cell fate commitment
digestive tract development
embryonic cranial skeleton morphogenesis
embryonic digestive tract morphogenesis
embryonic organ development
embryonic organ morphogenesis
embryonic pattern specification
epidermal growth factor receptor signaling pathway
epidermis morphogenesis
epithelial cell differentiation
epithelial cell proliferation involved in salivary gland morphogenesis
epithelial to mesenchymal transition
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway involved in hemopoiesis
fibroblast growth factor receptor signaling pathway involved in mammary gland specification
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow
gland morphogenesis
hair follicle morphogenesis
innate immune response
inner ear morphogenesis
insulin receptor signaling pathway
in utero embryonic development
lacrimal gland development
lateral sprouting from an epithelium
limb bud formation
lung alveolus development
lung-associated mesenchyme development
lung development
lung lobe morphogenesis
mammary gland bud formation
MAPK cascade
membranous septum morphogenesis
mesenchymal cell differentiation
mesenchymal cell differentiation involved in lung development
mesenchymal cell proliferation involved in lung development
mesodermal cell differentiation
midbrain development
morphogenesis of embryonic epithelium
multicellular organism growth
negative regulation of epithelial cell proliferation
negative regulation of transcription from RNA polymerase II promoter
neurotrophin TRK receptor signaling pathway
odontogenesis
orbitofrontal cortex development
organ growth
organ morphogenesis
otic vesicle formation
outflow tract septum morphogenesis
peptidyl-tyrosine phosphorylation
phosphatidylinositol-mediated signaling
positive regulation of canonical Wnt signaling pathway
positive regulation of cardiac muscle cell proliferation
positive regulation of cell cycle
positive regulation of cell division
positive regulation of cell proliferation
positive regulation of epithelial cell proliferation
positive regulation of epithelial cell proliferation involved in lung morphogenesis
positive regulation of ERK1 and ERK2 cascade
positive regulation of MAPK cascade
positive regulation of mesenchymal cell proliferation
positive regulation of phospholipase activity
positive regulation of smooth muscle cell proliferation
positive regulation of transcription from RNA polymerase II promoter
positive regulation of Wnt signaling pathway
post-embryonic development
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
prostate epithelial cord elongation
prostate gland morphogenesis
protein autophosphorylation
pyramidal neuron development
Ras protein signal transduction
regulation of branching involved in prostate gland morphogenesis
regulation of cell fate commitment
regulation of ERK1 and ERK2 cascade
regulation of fibroblast growth factor receptor signaling pathway
regulation of morphogenesis of a branching structure
regulation of multicellular organism growth
regulation of osteoblast differentiation
regulation of osteoblast proliferation
regulation of smoothened signaling pathway
regulation of smooth muscle cell differentiation
reproductive structure development
skeletal system morphogenesis
small GTPase mediated signal transduction
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development
ureteric bud development
vascular endothelial growth factor receptor signaling pathway
ventricular cardiac muscle tissue morphogenesis
ventricular zone neuroblast division - Gene Ontology Molecular Function:
- ATP binding
fibroblast growth factor-activated receptor activity
fibroblast growth factor binding
heparin binding
protein homodimerization activity
protein tyrosine kinase activity - Gene Ontology Cellular Component:
- cell cortex
cell surface
cytoplasm
cytoplasmic, membrane-bounded vesicle
excitatory synapse
extracellular region
Golgi apparatus
integral component of membrane
integral component of plasma membrane
intracellular membrane-bounded organelle
membrane
nucleoplasm
nucleus
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Apoptosis
Cell membrane
Complete proteome
Craniosynostosis
Cytoplasmic vesicle
Disease mutation
Disulfide bond
Ectodermal dysplasia
Glycoprotein
Golgi apparatus
Heparin-binding
Immunoglobulin domain
Kinase
Lacrimo-auriculo-dento-digital syndrome
Membrane
Mental retardation
Nucleotide-binding
Phosphoprotein
Polymorphism
Proto-oncogene
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation - Interacts With:
- P03968; P05230; O15520; P09038; P09038-2; P21781; P62993
Publication
- PubMed ID:
- 1697263 2172978 1647213 2377625 1313574 1400433 1309608 7866434 10626794 11856867 14702039 15164054 15489334 10712195 10196476 7668257 8676562 8673103 7581378 8961926 8663044 12529371 15190072 15629145 16597617 16844695 17623664 17311277 18374639 19410646 19103595 19369195 21596750 15863030 19387476 20094046 24275569 10830168 11069186 10618369 11390973 12591959 16384934 17803937 18056630 19060208 21454610 7987400 7874170 7655462 8528214 7719333 7719344 7719345 8644708 8946174 8956050 8696350 9150725 9385368 9002682 9152842 9677057 9521581 9452027 9693549 9719378 10574673 10394936 10945669 11173845 10951518 10633130 11380921 11781872 12000365 16061565 16501574 16959974 17344846 22387015