Characterization of three genes, AKAP84, BAW and WSB1, located 3 ' to the Neurofibromatosis type 1 locus in Fugu rubripes

Sequence analysis of cosmid clones was instrumental to identify three genes in the region flanking the Fugu rubripes NF1 gene in the 3' direction: the AKAP84 gene (A-kinase anchor protein 84), the WSB1 gene (WD-40-repeat prot ein with a SOCS box) and the BAW gene of yet unknown function located betwe en the AKAP84 and the WSB1 genes. The human homologues of these genes are n ot located in the immediate vicinity of the NF1 gene at 17q11.2. Although s ynteny of the NF1, AKAP84, BAW and WSB1 genes is conserved between Fugu and human, the gene order is not conserved, and more than a simple inversion w ould have been necessary to explain the difference in gene order. The mamma lian homologue of the Fugu BAW gene or protein has not yet been characteriz ed. As deduced from the respective cDNAs, the Fugu AKAP84, WSB1 and BAW pro teins vary concerning the overall degree of similarity to their mammalian c ounterparts. Whereas the overall similarity of AKAP84 between Fugu and mous e is low, three regions of known functional importance show considerable co nservation. These are the N-terminal anchoring domain mediating the inserti on of AKAP84 in the outer mitochondrial membrane, the binding site of the r egulatory subunit (RI or RII) of protein kinase A, and the C-terminal domai n present in the alternatively spliced isoform AKAP121 with an hnRNP K homo logy domain involved in RNA binding. A higher overall similarity of deduced protein sequences between Fugu and mouse was observed comparing the BAW ge ne products (74.1%) and the WSB1 proteins (77.2%). (C) 1999 Elsevier Scienc e B.V. All rights reserved.