Fibroblast growth factor receptor 3

FGFR3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RY7, 2LZL, 4K33
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]
Gene ontology Molecular function • transferase activity • nucleotide binding • protein kinase activity • kinase activity • protein binding • transmembrane receptor protein tyrosine kinase activity • fibroblast growth factor binding • fibroblast growth factor-activated receptor activity • ATP binding • protein tyrosine kinase activity • Ras guanyl-nucleotide exchange factor activity • phosphatidylinositol-4,5-bisphosphate 3-kinase activity • 1-phosphatidylinositol-3-kinase activity Cellular component • cytoplasm • integral component of membrane • Golgi apparatus • membrane • focal adhesion • plasma membrane • integral component of plasma membrane • transport vesicle • cytoplasmic, membrane-bounded vesicle • extracellular region • cell surface • endoplasmic reticulum • cytoplasmic vesicle • nucleus Biological process • skeletal system development • bone mineralization • JAK-STAT cascade • chondrocyte differentiation • phosphorylation • negative regulation of developmental growth • cell-cell signaling • bone morphogenesis • endochondral ossification • positive regulation of tyrosine phosphorylation of Stat3 protein • bone maturation • fibroblast growth factor receptor apoptotic signaling pathway • MAPK cascade • positive regulation of phosphatidylinositol 3-kinase activity • positive regulation of phospholipase activity • fibroblast growth factor receptor signaling pathway • protein phosphorylation • chondrocyte proliferation • positive regulation of cell proliferation • positive regulation of ERK1 and ERK2 cascade • protein autophosphorylation • peptidyl-tyrosine phosphorylation • endochondral bone growth • phosphatidylinositol-mediated signaling • positive regulation of tyrosine phosphorylation of Stat1 protein • positive regulation of MAPK cascade • apoptotic process • positive regulation of GTPase activity • phosphatidylinositol phosphorylation • regulation of phosphatidylinositol 3-kinase signaling • phosphatidylinositol-3-phosphate biosynthetic process Sources:Amigo / QuickGO
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 Human

View/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:

• achondroplasia/hypochondroplasia
• thanatophoric dwarfism
• seborrheic keratosis^[9]
• bladder cancer^[10]
• craniosynostosis^[11]
• SADDAN

Interactions

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

See also

• Cluster of differentiation
• Fibroblast growth factor receptor

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 50963. PMID 1847508.
5. 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. 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. 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 3240715. 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. 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. 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

• Schweitzer DN, Graham JM, Lachman RS, Jabs EW, Okajima K, Przylepa KA, Shanske A, Chen K, Neidich JA, Wilcox WR (January 2001). "Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3". American Journal of Medical Genetics. 98 (1): 75–91. doi:10.1002/1096-8628(20010101)98:1<75::AID-AJMG1010>3.0.CO;2-6. PMID 11426459.
• Horton WA, Lunstrum GP (December 2002). "Fibroblast growth factor receptor 3 mutations in achondroplasia and related forms of dwarfism". Reviews in Endocrine & Metabolic Disorders. 3 (4): 381–5. PMID 12424440.
• Bonaventure J, Silve C (November 2005). "[Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways]". Médecine Sciences. 21 (11): 954–61. doi:10.1051/medsci/20052111954. PMID 16274647.
• Hernández S, Toll A, Baselga E, Ribé A, Azua-Romeo J, Pujol RM, Real FX (July 2007). "Fibroblast growth factor receptor 3 mutations in epidermal nevi and associated low grade bladder tumors". The Journal of Investigative Dermatology. 127 (7): 1664–6. doi:10.1038/sj.jid.5700705. PMID 17255960.
• Olsen SK, Ibrahimi OA, Raucci A, Zhang F, Eliseenkova AV, Yayon A, Basilico C, Linhardt RJ, Schlessinger J, Mohammadi M (January 2004). "Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity". Proceedings of the National Academy of Sciences of the United States of America. 101 (4): 935–40. doi:10.1073/pnas.0307287101. PMC 327120. PMID 14732692.

External links

• GeneReviews/NIH/NCBI/UW entry on FGFR-Related Craniosynostosis Syndromes
• GeneReviews/NIH/NCBI/UW entry on Muenke Syndrome
• GeneReviews/NIH/NCBI/UW entry on Achondroplasia
• GeneReviews/NIH/NCBI/UW entry on Hypochondroplasia
• GeneReviews/NIH/NCBI/UW entry on Thanatophoric Dysplasia
• FGFR3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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