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, HSEX, JTK4
External IDs	MGI: MGI:95524 HomoloGene: 55437 GeneCards: 2261
Gene ontology Molecular function • transferase activity • nucleotide binding • protein kinase activity • kinase activity • protein binding • transmembrane receptor protein tyrosine kinase activity • protein tyrosine kinase activity • fibroblast growth factor binding • fibroblast growth factor-activated receptor activity • ATP binding 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 • insulin receptor signaling pathway • bone mineralization • JAK-STAT cascade • neurotrophin TRK receptor signaling pathway • chondrocyte differentiation • epidermal growth factor receptor signaling pathway • phosphorylation • activation of MAPKK activity • negative regulation of developmental growth • small GTPase mediated signal transduction • 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 • axon guidance • positive regulation of phosphatidylinositol 3-kinase activity • Fc-epsilon receptor signaling pathway • positive regulation of phospholipase activity • fibroblast growth factor receptor signaling pathway • protein phosphorylation • vascular endothelial growth factor receptor signaling pathway • chondrocyte proliferation • positive regulation of cell proliferation • positive regulation of ERK1 and ERK2 cascade • protein autophosphorylation • peptidyl-tyrosine phosphorylation • Ras protein signal transduction • innate immune response • endochondral bone growth • phosphatidylinositol-mediated signaling • positive regulation of tyrosine phosphorylation of Stat1 protein • positive regulation of MAPK cascade • apoptotic 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)	XM_011513422 NM_000142 NM_001163213 NM_022965 XM_006713868 XM_006713869 XM_006713870 XM_006713871 XM_006713872 XM_006713873 XM_011513420	NM_001163215 NM_001163216 NM_001163217 NM_001205270 NM_008010 XM_006503713 XM_006503714 XM_006503715 XM_006503716 XM_006503717 XM_006503718 XM_006503719 XM_006503720 XM_006503721 XM_006503722 XM_006503723 XM_006503724 XM_006503725 XM_006503726 XM_006503727 XM_006503728 XM_006503729 XM_006503730 XM_006503731 XM_006503732
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
Wikidata

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Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3 gene.^[1] FGFR3 has also been designated as CD333 (cluster of differentiation 333).

Structure and 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. Mutations in this gene lead to craniosynostosis and multiple types of skeletal dysplasia (Osteochondrodysplasia). 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.^[2]

The structure of the autophosphorylation of the kinase insert domain tyrosine residue, Tyr577, has been identified in PDB entry 4K33.^[3] This structure is very similar to the autophosphorylation complex of FGFR1^[4] as shown by a structural bioinformatics analysis.^[5]

Disease linkage

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

• achondroplasia/hypochondroplasia
• thanatophoric dwarfism
• seborrheic keratosis^[6]
• bladder cancer^[7]
• craniosynostosis^[8]

Interactions

Fibroblast growth factor receptor 3 has been shown to interact with FGF1^[9][10] and FGF9.^[9][10]

See also

• Cluster of differentiation
• Fibroblast growth factor receptor

References

1. Keegan K, Johnson DE, Williams LT, Hayman MJ (Mar 1991). "Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3". Proc Natl Acad Sci U S A 88 (4): 1095–9. doi:10.1073/pnas.88.4.1095. PMC 50963. PMID 1847508.
2. "Entrez Gene: FGFR3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism)".
3. Huang, Z; Chen, H; Blais, S; Neubert, TA; Li, X; Mohammadi, M (8 October 2013). "Structural mimicry of a-loop tyrosine phosphorylation by a pathogenic FGF receptor 3 mutation.". Structure (London, England : 1993) 21 (10): 1889–96. PMID 23972473.
4. Bae, JH; Lew, ED; Yuzawa, S; Tomé, F; Lax, I; Schlessinger, J (7 August 2009). "The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.". Cell 138 (3): 514–24. PMID 19665973.
5. Xu, Q; Malecka, KL; Fink, L; Jordan, EJ; Duffy, E; Kolander, S; Peterson, JR; Dunbrack RL, Jr (1 December 2015). "Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases.". Science signaling 8 (405): rs13. PMID 26628682.
6. Hafner C, Hartmann A, Vogt T (2007). "FGFR3 mutations in epidermal nevi and seborrheic keratoses: lessons from urothelium and skin". J. Invest. Dermatol. 127 (7): 1572–3. doi:10.1038/sj.jid.5700772. PMID 17568799.
7. Lamy A, Gobet F, Laurent M; et al. (2006). "Molecular profiling of bladder tumors based on the detection of FGFR3 and TP53 mutations". J. Urol. 176 (6 Pt 1): 2686–9. doi:10.1016/j.juro.2006.07.132. PMID 17085196.
8. Mulliken, JB (Nov 1999). "Molecular diagnosis of bilateral coronal synostosis". Plast Reconstr Surg. 104 (6): 1603–1615. PMID 10541159. Retrieved 30 October 2014.
9. Santos-Ocampo, S; Colvin J S; Chellaiah A; Ornitz D M (Jan 1996). "Expression and biological activity of mouse fibroblast growth factor-9". J. Biol. Chem. (UNITED STATES) 271 (3): 1726–31. doi:10.1074/jbc.271.3.1726. ISSN 0021-9258. PMID 8576175.
10. Chellaiah, A; Yuan W; Chellaiah M; Ornitz D M (Dec 1999). "Mapping ligand binding domains in chimeric fibroblast growth factor receptor molecules. Multiple regions determine ligand binding specificity". J. Biol. Chem. (UNITED STATES) 274 (49): 34785–94. doi:10.1074/jbc.274.49.34785. ISSN 0021-9258. PMID 10574949.

Further reading

• Schweitzer DN, Graham JM, Lachman RS; et al. (2001). "Subtle radiographic findings of achondroplasia in patients with Crouzon syndrome with acanthosis nigricans due to an Ala391Glu substitution in FGFR3.". Am. J. Med. Genet. 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 (2003). "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 (2006). "[Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways]". Med Sci (Paris) 21 (11): 954–61. doi:10.1051/medsci/20052111954. PMID 16274647.
• Hernández S, Toll A, Baselga E; et al. (2007). "Fibroblast growth factor receptor 3 mutations in epidermal nevi and associated low grade bladder tumors.". J. Invest. Dermatol. 127 (7): 1664–6. doi:10.1038/sj.jid.5700705. PMID 17255960.
• Olsen SK; et al. (2004). "Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity.". PNAS USA 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.