FMNL1, FMNL2, FMNL3, DAAM1, DAAM2, DIAPH1 and DIAPH2 constitute the Formin-homology subfamily with FDD, FH1 and FH2 domains. FMNL2 gene is linked to FNBP3 (also known as HYPA) gene on human chromosome 2q23.3, while FMNL3 gene to FNBP3L (also known as HYPC) gene on 12q13. Because human FNBP3 cDNA (NM_017892.2) was a 5'-truncated partial clone, we identified and characterized human FNBP3 gene by using bioinformatics. Human FNBP3 gene, consisting of 26 exons, was located within human genome sequences AC079344.5, AC012443.8, and human chromosome 2 genomic contig NT_005403.13. Nucleotide sequence of human FNBP3 cDNA was determined in silico by assembling nucleotide sequences of 26 exons of FNBP3 gene. HYPA cDNA and IMAGE cDNA clones 3356968, 4026200, 4733897 were 3'-truncated partial FNBP3 cDNAs, while FNBP3 (NM_017892.2), FLJ11559, NY-REN-6, and FLJ20585 were 5'-truncated partial FNBP3 cDNAs. Two FNBP3 isoforms with or without 126-bp region in the 3'-part of exon 1 were transcribed due to alternative splicing. FNBP3 isoform 2 without the 126-bp region was the major FNBP3 transcript. Two WW domains, two FF domains, two bipartite nuclear localization signals, FB3HM and FB3HC domains were conserved among vertebrate FNBP3 homologs, including human FNBP3, FNBP3L, mouse Fnbp3, Fnbp3l, chicken fnbp3 and zebrafish fnbp3. FNBP3, binding to TNFSF6 (Fas ligand), Huntingtin and Formin proteins, might transduce extracellular signals to the Rho-related signaling pathway. On the other hand, FNBP3 with nuclear localization signals and two tyrosine phosphorylation sites might transduce extracellular signals to the nucleus. This is the first report on comprehensive characterization of human FNBP3 gene.

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