Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Narashino 275-0022, Japan.
Int J Mol Med. 2003 Oct;12(4):651-6.
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.
FMNL1、FMNL2、FMNL3、DAAM1、DAAM2、DIAPH1和DIAPH2构成了具有FDD、FH1和FH2结构域的formin同源亚家族。FMNL2基因与人类染色体2q23.3上的FNBP3(也称为HYPA)基因相连,而FMNL3基因与12q13上的FNBP3L(也称为HYPC)基因相连。由于人类FNBP3 cDNA(NM_017892.2)是一个5'端截短的部分克隆,我们利用生物信息学鉴定并表征了人类FNBP3基因。人类FNBP3基因由26个外显子组成,位于人类基因组序列AC079344.5、AC012443.8以及人类染色体2基因组重叠群NT_005403.13内。通过组装FNBP3基因26个外显子的核苷酸序列,在计算机上确定了人类FNBP3 cDNA的核苷酸序列。HYPA cDNA以及IMAGE cDNA克隆3356968、4026200、4733897是3'端截短的部分FNBP3 cDNA,而FNBP3(NM_017892.2)、FLJ11559、NY-REN-6和FLJ20585是5'端截短的部分FNBP3 cDNA。由于选择性剪接,转录出了两种在第1外显子3'部分有或没有126bp区域的FNBP3异构体。没有126bp区域的FNBP3异构体2是主要的FNBP3转录本。在包括人类FNBP3、FNBP3L、小鼠Fnbp3、Fnbp3l、鸡fnbp3和斑马鱼fnbp3在内的脊椎动物FNBP3同源物中,两个WW结构域、两个FF结构域、两个双分型核定位信号、FB3HM和FB3HC结构域是保守的。与TNFSF6(Fas配体)、亨廷顿蛋白和formin蛋白结合的FNBP3可能将细胞外信号转导至Rho相关信号通路。另一方面,具有核定位信号和两个酪氨酸磷酸化位点的FNBP3可能将细胞外信号转导至细胞核。这是关于人类FNBP3基因全面表征的首次报道。