Fibroblast growth factor receptor 3

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FGFR3
PDB 1ry7 EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases FGFR3, ACH, CD333, CEK2, HSFGFR3EX, JTK4, fibroblast growth factor receptor 3
External IDs MGI: 95524 HomoloGene: 55437 GeneCards: FGFR3
Gene location (Human)
Chromosome 4 (human)
Chr. Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for FGFR3
Genomic location for FGFR3
Band 4p16.3 Start 1,793,307 bp[1]
End 1,808,872 bp[1]
RNA expression pattern
PBB GE FGFR3 204380 s at fs.png

PBB GE FGFR3 204379 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000142
NM_001163213
NM_022965
NM_001354809
NM_001354810

NM_001163215
NM_001163216
NM_001163217
NM_001205270
NM_008010

RefSeq (protein)

NP_000133
NP_001156685
NP_075254
NP_001341738
NP_001341739

n/a

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

Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3 gene.[5] FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene, which is located on chromosome 4, location p16.3, is "expressed in tissues such as the cartilage, brain, intestine, and kidneys."[6]

Function[edit]

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.[7]

Mutations[edit]

Mutations in this gene can develop dysfunctional proteins "impede cartilage growth and development and affect chondrocyte proliferation and calcification"[6] 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".[8] By inhibiting chondrocyte proliferation, FGFR3 restricts long bone length.[9] In achondroplasia, the FGFR3 gene has a point mutation at nucleotide 1138 resulting from either a G>A or G>C.[9] FGFR3 mutations are linked with spermatocytic seminoma, which occur more frequently in older men.[8]

Disease linkage[edit]

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

Interactions[edit]

Fibroblast growth factor receptor 3 has been shown to interact with FGF1[13][14] and FGF9.[13][14]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000068078 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000054252 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ 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. PMC 50963Freely accessible. PMID 1847508. doi:10.1073/pnas.88.4.1095. 
  6. ^ a b 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.
  7. ^ "Entrez Gene: FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)". 
  8. ^ a b 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. PMID 23880303. doi:10.1093/carcin/bgt254. 
  9. ^ a b 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. PMC 3240715Freely accessible. PMID 22045636. doi:10.1002/humu.21636. 
  10. ^ 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. PMID 17568799. doi:10.1038/sj.jid.5700772. 
  11. ^ 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. PMID 17085196. doi:10.1016/j.juro.2006.07.132. 
  12. ^ Mulliken JB, Steinberger D, Kunze S, Müller U (November 1999). "Molecular diagnosis of bilateral coronal synostosis". Plastic and Reconstructive Surgery. 104 (6): 1603–15. PMID 10541159. doi:10.1097/00006534-199911000-00001. 
  13. ^ a b 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. PMID 8576175. doi:10.1074/jbc.271.3.1726. 
  14. ^ a b 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. PMID 10574949. doi:10.1074/jbc.274.49.34785. 

Further reading[edit]

External links[edit]

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