Bioinformatics Database
FGFR2: Fibroblast growth factor receptor 2
Cellular Process
Bud stage of tooth development
Gene Name
FGFR2: Fibroblast growth factor receptor 2
Gene ID
2263
Gene Sequence
General Description
The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member is a high-affinity receptor for acidic, basic and/or keratinocyte growth factor, depending on the isoform.
Alternative titles; symbols
FGF RECEPTOR PROTEIN TYROSINE KINASE, RECEPTOR-LIKE, 14; TK14
Chromosome
Chromosome 10
Cytogenetic location
10q26.13
Encoded Protein
Fibroblast growth factor receptor 2 isoform 1 precursor https://www.ncbi.nlm.nih.gov/protein/NP_000132.3/
Function of the protein in oral and tooth development
In a study by Rice et al., (2004), Fgf10 -/-, Fgfr2b -/-, and Sonic hedgehog (SHH) -/- mice exhibited cleft palate. The results showed that Shh is a downstream target of Fgf10/Fgfr2b signaling (Rice et al, 2004). Mesenchymal Fgf10 was found to regulate the epithelial expression of Shh, which in turn signals back to the mesenchyme. This was confirmed by the finding that cell proliferation was decreased not only in the palatal epithelium but also in the mesenchyme of Fgfr2b -/- mice (Rice et al, 2004). The findings of the study indicated that coordinated epithelial-mesenchymal interactions are essential during the initial stages of palate development and require an FGF-SHH signaling network (Rice et al., 2004).
Dental and Oral Diseases
Apert syndrome: Apert syndrome, also called acrocephalosyndactyly, is a genetic syndrome characterized by anomalies of the skull, face and limbs. Gene mutations are responsible for causing the early fusion of the skull, hand and feet bones. Two activating mutations in FGFR2, ser252 to trp and pro253 to arg, cause Apert syndrome. These structures of FGFR2 mutants demonstrate that both mutations introduce additional interactions between FGFR2 and FGF2, increasing FGFR2-FGF2 affinity. The distinct gain-of-function interactions observed in each crystal structure provide a model to explain the phenotypic variability among Apert syndrome patients. For example, patients with the ser252-to-trp mutation present more frequently with cleft palate, whereas patients with the pro253-to-arg mutation exhibit more severe syndactyly (Syndactyly is the medical term for webbed or conjoined fingers or toes) (Slaney et al., 1996; Lajeunie et al., 1999).
Protein Sequence
>NP_000132.3 fibroblast growth factor receptor 2 isoform 1 precursor [Homo sapiens]
MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGESLEVRCLLKDAAVI
SWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETWYFMVNVTDAISSGDDEDDTDGA
EDFVSENSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVR
NQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKV
YSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGI
SFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTK
RIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEG
CFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPL
YVIVEYASKGNLREYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAAR
NVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLG
GSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYL
DLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT
Mutations
Apert syndrome:
SER252TRP: Wilkie et al. (1995) identified a heterozygous 934C-G transversion in the FGFR2 gene, resulting in a ser252-to-trp (S252W) substitution within a highly conserved linker region between the second and third extracellular immunoglobulin (Ig) domains of the protein. Among 70 unrelated patients with Apert syndrome, Slaney et al. (1996) found that 45 had the S252W mutation and 25 had the P253R mutation. The syndactyly of the hands and feet was more severe in those with the P253R mutation. In contrast, cleft palate was significantly more common in patients with the S252W patients.
Related Literature
Rice et al., (2004).https://doi.org/10.1172/JCI20384
Slaney et al. (1996). Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome. American journal of human genetics, 58(5), 923–932.
Lajeunie et al. (1999). https://doi.org/10.3171/jns.1999.90.3.0443
Wilkie et al, (1995). https://doi.org/10.1038/ng0295-165
