Phylogenetic analysis of receptor FgfrL1 shows divergence of the C-terminal end in rodents.
FGFRL1 is a member of the fibroblast growth factor receptor (FGFR) family. Similar to the classical receptors FGFR1-FGFR4, it contains three extracellular Ig-like domains and a single transmembrane domain. However, it lacks the intracellular tyrosine kinase domain that would be required for signal transduction, but instead contains a short intracellular tail with a peculiar histidine-rich motif. This motif has been conserved during evolution from mollusks to echinoderms and vertebrates. Only the sequences of FgfrL1 from a few rodents diverge at the C-terminal region from the canonical sequence, as they appear to have suffered a frameshift mutation within the histidine-rich motif. This mutation is observed in mouse, rat and hamster, but not in the closely related rodents mole rat (Nannospalax) and jerboa (Jaculus), suggesting that it has occurred after branching of the Muridae and Cricetidae from the Dipodidae and Spalacidae. The consequence of the frameshift is a deletion of a few histidine residues and an extension of the C-terminus by about 40 unrelated amino acids. A similar frameshift mutation has also been observed in a human patient with a craniosynostosis syndrome as well as in several patients with colorectal cancer and bladder tumors, suggesting that the histidine-rich motif is prone to mutation. The reason why this motif was conserved during evolution in most species, but not in mice, is not clear.
Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
Lei
L
Zhuang
Department of Clinical Research, University of Bern, 3010 Bern, Switzerland.
Gilles
G
Bluteau
Department of Clinical Research, University of Bern, 3010 Bern, Switzerland; Department of Rheumatology, University Hospital, 3010 Bern, Switzerland. Electronic address: beat.trueb@dkf.unibe.ch.
Beat
B
Trueb
D000818:Animals; D006639:Histidine / Q000235:genetics; D006801:Humans; D007448:Invertebrates; D051379:Mice / Q000235:genetics*; D009154:Mutation; D017434:Protein Structure, Tertiary; D051500:Receptor, Fibroblast Growth Factor, Type 5 / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014714:Vertebrates
C496379:Fgfrl1 protein, mouse; D051500:Receptor, Fibroblast Growth Factor, Type 5; D006639:Histidine
FGFRL1; Fibroblast growth factor (FGF); Fibroblast growth factor receptor (FGFR); Histidine-rich motif; Rodents