Fibroblast growth factor receptor 1, catalytic domain (IPR028174)

Short name: FGF_rcpt_1

Overlapping homologous superfamilies

Domain relationships


Fibroblast growth factors (FGFs) [PMID: 2549857, PMID: 3072709] are a family of multifunctional proteins, often referred to as 'promiscuous growth factors' due to their diverse actions on multiple cell types [PMID: 1705486, PMID: 8760337]. FGFs are mitogens, which stimulate growth or differentiation of cells of mesodermal or neuroectodermal origin. The function of FGFs in developmental processes include mesoderm induction, anterior-posterior patterning, limb development, and neural induction and development. In mature tissues, they are involved in diverse processes including keratinocyte organisation and wound healing [PMID: 11276432, PMID: 23000357, PMID: 15689573, PMID: 10441498, PMID: 23108135, PMID: 23016864]. FGF involvement is critical during normal development of both vertebrates and invertebrates, and irregularities in their function leads to a range of developmental defects [PMID: 1649700, PMID: 11746231, PMID: 14745970, PMID: 8978613]. Fibroblast growth factors are heparin-binding proteins and interactions with cell-surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction. FGFs have internal pseudo-threefold symmetry (beta-trefoil topology) [PMID: 10830168]. There are currently over 20 different FGF family members that have been identified in mammals, all of which are structurally related signaling molecules [PMID: 8652550, PMID: 11276432]. They exert their effects through four distinct membrane fibroblast growth factor receptors (FGFRs), FGFR1 to FGFR4 [PMID: 7583099], which belong to the tyrosine kinase superfamily. Upon binding to FGF, the receptors dimerize and their intracellular tyrosine kinase domains become active [PMID: 7583099].

The FGFRs consist of an extracellular ligand-binding domain composed of three immunoglobulin-like domains (D1-D3), a single transmembrane helix domain, and an intracellular domain with tyrosine kinase activity [PMID: 18216218]. The three immunoglobin(Ig)-like domains, D1, D2, and D3, present a stretch of acidic amino acids (known as the acid box) between D1 and D2. This acid box can participate in the regulation of FGF binding to the FGFR. Immunoglobulin-like domains D2 and D3 are sufficient for FGF binding. FGFR family members differ from one another in their ligand affinities and tissue distribution [PMID: 16597617, PMID: 9212826]. Most FGFs can bind to several different FGFR subtypes. Indeed, FGF1 is sometimes referred to as the universal ligand, as it is capable of activating all of the different FGFRs [PMID: 8663044]. However, there are some exceptions. For example, FGF7 only interacts with FGFR2 [PMID: 16829530] and FGF18 was recently shown to only activate FGFR3 [PMID: 15781473].

Fibroblast growth factor receptor 1 (FGFR1) binds both acidic and basic fibroblast growth factors and is involved in limb induction [PMID: 16207751]. FGFR1 has been shown to be associated with Pfeiffer syndrome [PMID: 2162671], and cleft lip and/or palate [PMID: 17360555, PMID: 21331089]. Fibroblast growth factor receptor 1 has been shown to interact with growth factor receptor-bound protein 14 (GRB14) [PMID: 10713090], Src homology 2 domain containing adaptor protein B (SHB) [PMID: 7537362], fibroblast growth factor receptor substrate 2 (FRS2)[PMID: 10629055] and fibroblast growth factor 1 (FGF1) [PMID: 11030354, PMID: 8576175].

This entry represents the catalytic domain of FGFR1.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0005007 fibroblast growth factor-activated receptor activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.