Katoh Yuriko, Katoh Masaru
M&M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Oncol. 2005 Sep;27(3):861-5.
SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, WIF1, DKK1, DKK2, DKK3, DKK4 are secreted-type WNT signaling modulators. SFRP1 tumor suppressor gene at human chromosome 8p11.21 is inactivated in colorectal cancer and other tumors by deletion and by epigenetic CpG hypermethylation. Here, we identified and characterized the rat Sfrp1 gene by using bioinformatics. Rat Sfrp1 gene, consisting of three exons, was located within AC112899.4 genome sequence. Complete coding sequence of rat Sfrp1 was determined by assembling AC112899.4 genome sequence, CK838748 EST, and BF417482 EST. Rat Sfrp1 (314 aa) consisted of a signal peptide (codon 1-31), Frizzled domain with ten conserved Cys residues (codon 49-168), and Netrin (NTR) domain with six conserved Cys residues (codon 186-314). Rat Sfrp1 showed 98.7%, 95.2%, 94.3%, 82.5% and 58.3% total-amino-acid identity with mouse Sfrp1, human SFRP1, cow Sfrp1, chicken sfrp1 and zebrafish sfrp1, respectively. SFRP1 mRNA was expressed in embryonic stem (ES) cells, neuroblastoma, liver adeno-carcinoma, and skin squamous cell carcinoma. Match program revealed that AP1, COMP1, and double ETS1-binding sites were conserved between human SFRP1 and rat Sfrp1 promoters. This is the first report on comparative integromics analyses on Sfrp1 orthologs.
分泌型卷曲相关蛋白1（SFRP1）、分泌型卷曲相关蛋白2（SFRP2）、分泌型卷曲相关蛋白3（SFRP3）、分泌型卷曲相关蛋白4（SFRP4）、分泌型卷曲相关蛋白5（SFRP5）、Wnt抑制因子1（WIF1）、Dickkopf相关蛋白1（DKK1）、Dickkopf相关蛋白2（DKK2）、Dickkopf相关蛋白3（DKK3）、Dickkopf相关蛋白4（DKK4）是分泌型WNT信号调节剂。人染色体8p11.21上的SFRP1肿瘤抑制基因在结直肠癌和其他肿瘤中因缺失和表观遗传的CpG高甲基化而失活。在此，我们通过生物信息学鉴定并表征了大鼠Sfrp1基因。大鼠Sfrp1基因由三个外显子组成，位于AC112899.4基因组序列内。大鼠Sfrp1的完整编码序列是通过组装AC112899.4基因组序列、CK838748 EST和BF417482 EST确定的。大鼠Sfrp1（314个氨基酸）由一个信号肽（第1 - 31密码子）、一个具有十个保守半胱氨酸残基的卷曲蛋白结构域（第49 - 168密码子）和一个具有六个保守半胱氨酸残基的网蛋白（NTR）结构域（第186 - 314密码子）组成。大鼠Sfrp1与小鼠Sfrp1、人SFRP1、牛Sfrp1、鸡sfrp1和斑马鱼sfrp1的总氨基酸同一性分别为98.7%、95.2%、94.3%、82.5%和58.3%。SFRP1 mRNA在胚胎干细胞、神经母细胞瘤、肝腺癌和皮肤鳞状细胞癌中表达。比对程序显示，人SFRP1和大鼠Sfrp1启动子之间的激活蛋白1（AP1）、COMP1和双Ets1结合位点是保守的。这是关于Sfrp1直系同源物的比较整合组学分析的首次报告。
