Characterization of the Fugu rubripes NLK and FN5 genes flanking the NF1 (neurofibromatosis type 1) gene in the 5 ' direction and mapping of the human counterparts

To complete the analysis of the Neurofibromatosis type 1 (NF1) gene region in Fugu rubripes, we characterized the upstream flanking legion of the NF1 gene and identified the FN5 (flanking the Fugu NF1 gene in 5' direction) ge ne and the NLK (Nemo-like kinase) gene as its flanking genes. The FN5 gene spans 3807 bp and encompasses four exons, three of which belong to the expa nded 5' UTR. Only 11% of the FN5 transcript is protein-coding. The function of the FN5 protein spanning 59 amino acids is unknown. We also characteriz ed the human and the mouse FN5 transcripts and found 85% and 83% similarity of deduced amino acid sequences compared with Fugu. Two copies of the huma n FN5 gene were identified, one on chromosome 17q21.3-q73 several megabases distal to the NF1 gene at 17q11.2. The second copy of the FN5 gene was map ped to 11q13.3-q23.3. In Fugu, the FN5 gene is flanked by the NLK gene, whi ch spans 4513 bp from the translation start to the stop codon and encompass es 11 exons. Comparing the deduced amino acid sequences, 82% overall simila rity was observed between Fugu and mouse or human NLK and 67% similarity be tween the Fugu NLK and the highly related LIT-1 kinase of Caenorhabditis el egans, which has been shown, like the vertebrate counterpart, to be involve d in the Wnt signalling pathway. We mapped the human NLK gene to 17q11.2 be tween markers D17S935 and D17S120, more than 1 Mb proximal to the NF1 gene. The characterization of the 5' flanking region presented here, together wi th that of the 3' region, demonstrates the profound differences between Fug u and human considering the gene content within the region flanking the NF1 gene. (C) 2000 Elsevier Science B.V. All rights reserved.