Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Narashino 275-0022, Japan.
Int J Oncol. 2003 Apr;22(4):907-13.
WNT signals play key roles in carcinogenesis and embryogenesis through the specification of cell fate and polarity. Dishevelled (DVL) proteins are WNT signaling molecules implicated in beta-catenin pathway and PCP pathway. Xenopus Dapper and Frodo are Dvl-binding proteins, showing 89.8% total-amino-acid identity. Here, we identified and characterized human homologs of Xenopus Dapper and Frodo using bioinformatics. Human DAPPER1 gene was located within human genome draft sequence NT_025892.9 (nucleotide position 39378960-39387891 in the forward orientation), and human DAPPER2 gene within NT_007302.10 (nucleotide position 660279-672480 in the reverse orientation). DAPPER1 (799-amino-acids) and DAPPER2 (774-amino-acids) showed 28.8% total-amino-acid identity. Seven DAPPER homologous (DAPH) domains, including DAPH2 (leucine zipper), DAPH3 (serine rich) and DAPH7 (PDZ binding), were conserved between DAPPER1 and DAPPER2. Phylogenetic analysis of vertebrate Dapper proteins revealed that Xenopus Dapper and Frodo are orthologs of human DAPPER1. DAPPER1 mRNA was expressed in amnion, fetal brain, eye, heart, adult brain medulla, gastric cancer (signet ring cell features), RER+ colon tumor, acute lymphoblastic leukemia, germ cell tumor, chondrosarcoma, and parathyroid tumor. DAPPER2 mRNA was expressed in placenta, genitourinary tract tumor, and endometrial adenocarcinoma. DAPPER1 and DAPPER2 genes were mapped to human chromosome 14q22.3 and 6q27, respectively. Human chromosome 14q22.3 is deleted in astrocytoma, while human chromosome 6q27 is deleted in breast, ovarian, and gastric cancer. Based on evolutionary and functional conservation of WNT signaling molecules as well as human chromosomal localization, DAPPER1 and DAPPER2 genes are predicted to be potent cancer-associated genes.
WNT信号通过细胞命运和极性的特化在致癌作用和胚胎发生中发挥关键作用。蓬乱蛋白（DVL）是涉及β-连环蛋白途径和平面细胞极性（PCP）途径的WNT信号分子。非洲爪蟾的Dapper和Frodo是与Dvl结合的蛋白，其总氨基酸同一性为89.8%。在此，我们利用生物信息学鉴定并表征了非洲爪蟾Dapper和Frodo的人类同源物。人类DAPPER1基因位于人类基因组草图序列NT_025892.9内（正向方向的核苷酸位置为39378960 - 39387891），人类DAPPER2基因位于NT_007302.10内（反向方向的核苷酸位置为660279 - 672480）。DAPPER1（799个氨基酸）和DAPPER2（774个氨基酸）的总氨基酸同一性为28.8%。DAPPER1和DAPPER2之间保守存在七个DAPPER同源（DAPH）结构域，包括DAPH2（亮氨酸拉链）、DAPH3（富含丝氨酸）和DAPH7（PDZ结合）。对脊椎动物Dapper蛋白的系统发育分析表明，非洲爪蟾的Dapper和Frodo是人类DAPPER1的直系同源物。DAPPER1 mRNA在羊膜、胎儿脑、眼、心脏、成人大脑髓质、胃癌（印戒细胞特征）、粗面内质网阳性结肠肿瘤、急性淋巴细胞白血病、生殖细胞肿瘤、软骨肉瘤和甲状旁腺肿瘤中表达。DAPPER2 mRNA在胎盘、泌尿生殖道肿瘤和子宫内膜腺癌中表达。DAPPER1和DAPPER2基因分别定位于人类染色体14q22.3和6q27。星形细胞瘤中人类染色体14q22.3缺失，而乳腺癌、卵巢癌和胃癌中人类染色体6q27缺失。基于WNT信号分子的进化和功能保守性以及人类染色体定位，预测DAPPER1和DAPPER2基因为潜在癌症相关基因。
