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FGFR2 mutated K659N

Domain

The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity.

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, 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.

Involvement in disease

Crouzon syndrome

CS

An autosomal dominant syndrome characterized by craniosynostosis, hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.

None

The disease is caused by variants affecting the gene represented in this entry.

Jackson-Weiss syndrome

JWS

An autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.

None

The disease is caused by variants affecting the gene represented in this entry.

Apert syndrome

APRS

A 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.

None

The disease is caused by variants affecting the gene represented in this entry.

Pfeiffer syndrome

PS

A 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).

None

The disease is caused by variants affecting the gene represented in this entry.

Beare-Stevenson cutis gyrata syndrome

BSTVS

An 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.

None

The disease is caused by variants affecting the gene represented in this entry.

Familial scaphocephaly syndrome

FSPC

An 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.

None

The disease is caused by variants affecting the gene represented in this entry.

Lacrimo-auriculo-dento-digital syndrome 1

LADD1

A form of lacrimo-auriculo-dento-digital syndrome, an autosomal dominant disease 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.

None

The disease is caused by variants affecting the gene represented in this entry.

Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis

ABS2

A 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.

None

The disease is caused by variants affecting the gene represented in this entry.

Bent bone dysplasia syndrome 1

BBDS1

A 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.

None

The disease is caused by variants affecting the gene represented in this entry.

Saethre-Chotzen syndrome

SCS

A craniosynostosis syndrome characterized by coronal synostosis, brachycephaly, low frontal hairline, facial asymmetry, hypertelorism, broad halluces, and clinodactyly.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.

Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.

Cellular localization

  • Cell membrane
  • Single-pass type I membrane protein
  • Golgi apparatus
  • Cytoplasmic vesicle
  • 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
  • After ligand binding, the activated receptor is rapidly internalized and degraded.
  • Isoform 3
  • Cell membrane
  • Single-pass type I membrane protein
  • After ligand binding, the activated receptor is rapidly internalized and degraded.
  • Isoform 8
  • Secreted
  • Isoform 13
  • Secreted

Alternative names

CD332, BEK, KGFR, KSAM, FGFR2, Fibroblast growth factor receptor 2, FGFR-2, K-sam, Keratinocyte growth factor receptor

Target type

Proteins

Primary research area

Oncology

Molecular weight

92025Da

We found 1 product in 1 category

Proteins & Peptides

Target

Species of origin

Search our catalogue for 'FGFR2 mutated K659N' (1)

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