Fibroblast growth factor receptor 3

FGFR3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases FGFR3, ACH, CD333, CEK2, HSFGFR3EX, JTK4, fibroblast growth factor receptor 3
External IDs MGI: 95524 HomoloGene: 55437 GeneCards: FGFR3
Targeted by Drug
nintedanib[1]
RNA expression pattern


More reference expression data
Orthologs
Species Human Mouse
Entrez

2261

14184

Ensembl

ENSG00000068078

ENSMUSG00000054252

UniProt

P22607

Q61851

RefSeq (mRNA)

NM_000142
NM_001163213
NM_022965

NM_001163215
NM_001163216
NM_001163217
NM_001205270
NM_008010

RefSeq (protein)

NP_000133.1
NP_001156685.1
NP_075254.1

n/a

Location (UCSC) Chr 4: 1.79 – 1.81 Mb Chr 5: 33.72 – 33.74 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3 gene.[4] FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene is located on chromosome 4q16.3 is "expressed in tissues such as the cartilage, brain, intestine, and kidneys."[5]

Function

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 would consist 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 which ultimately influencing cell mitogenesis and differentiation.

This particular family member binds both acidic and basic fibroblast growth factor and plays a role in bone development and maintenance. Alternative splicing occurs and additional variants have been described, including those utilizing alternate exon 8 rather than 9, but their full-length nature has not been determined.[6]

Mutations

Mutations in this gene can develop dysfunctional proteins "impede cartilage growth and development and affect chondrocyte proliferation and calcification"[5] which can lead to craniosynostosis and multiple types of skeletal dysplasia (Osteochondrodysplasia). The point mutation in the FGFR3 gene causes hydrogen bonds to form between two arginine side chains leading to ligand-independent stabilization FGFR3 dimers. Point mutations in the FGFR3 gene, “causes defective growth of long tubular bones”.[7] By inhibiting chondrocyte proliferation, FGFR3 restricts long bone length.[8] In achondroplasia, the FGFR3 gene has a point mutation at nucleotide 1138 resulting from either a G>A or G>C.[8] FGFR3 mutations are linked with spermatocytic summons, which occur more frequently in older men.[7]

Disease linkage

Defects in the FGFR3 gene has been associated with several conditions, including:

Interactions

Fibroblast growth factor receptor 3 has been shown to interact with FGF1[12][13] and FGF9.[12][13]

See also

References

  1. "Drugs that physically interact with Fibroblast growth factor receptor 3 view/edit references on wikidata".
  2. "Human PubMed Reference:".
  3. "Mouse PubMed Reference:".
  4. Keegan K, Johnson DE, Williams LT, Hayman MJ (February 1991). "Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3". Proceedings of the National Academy of Sciences of the United States of America. 88 (4): 1095–9. doi:10.1073/pnas.88.4.1095. PMC 50963Freely accessible. PMID 1847508.
  5. 1 2 Wang, Y., Liu, Z., Liu, Z., Zhao, H., Zhou, X., Cui, Y., & Han, J. (2013). Advances in research on and diagnosis and treatment of achondroplasia in China. Intractable & Rare Diseases Research, 2(2), 45-50.
  6. "Entrez Gene: FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)".
  7. 1 2 Kelleher FC, O'Sullivan H, Smyth E, McDermott R, Viterbo A (2013). "Fibroblast growth factor receptors, developmental corruption and malignant disease". Carcinogenesis. 34 (10): 2198–205. doi:10.1093/carcin/bgt254. PMID 23880303.
  8. 1 2 Foldynova-Trantirkova S, Wilcox WR, Krejci P (2012). "Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias". Human Mutation. 33 (1): 29–41. doi:10.1002/humu.21636. PMC 3240715Freely accessible. PMID 22045636.
  9. Hafner C, Hartmann A, Vogt T (July 2007). "FGFR3 mutations in epidermal nevi and seborrheic keratoses: lessons from urothelium and skin". The Journal of Investigative Dermatology. 127 (7): 1572–3. doi:10.1038/sj.jid.5700772. PMID 17568799.
  10. Lamy A, Gobet F, Laurent M, Blanchard F, Varin C, Moulin C, Andreou A, Frebourg T, Pfister C (December 2006). "Molecular profiling of bladder tumors based on the detection of FGFR3 and TP53 mutations". The Journal of Urology. 176 (6 Pt 1): 2686–9. doi:10.1016/j.juro.2006.07.132. PMID 17085196.
  11. Mulliken JB, Steinberger D, Kunze S, Müller U (November 1999). "Molecular diagnosis of bilateral coronal synostosis". Plastic and Reconstructive Surgery. 104 (6): 1603–15. doi:10.1097/00006534-199911000-00001. PMID 10541159.
  12. 1 2 Santos-Ocampo S, Colvin JS, Chellaiah A, Ornitz DM (January 1996). "Expression and biological activity of mouse fibroblast growth factor-9". The Journal of Biological Chemistry. 271 (3): 1726–31. doi:10.1074/jbc.271.3.1726. PMID 8576175.
  13. 1 2 Chellaiah A, Yuan W, Chellaiah M, Ornitz DM (December 1999). "Mapping ligand binding domains in chimeric fibroblast growth factor receptor molecules. Multiple regions determine ligand binding specificity". The Journal of Biological Chemistry. 274 (49): 34785–94. doi:10.1074/jbc.274.49.34785. PMID 10574949.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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