Katoh Masuko, Katoh Masaru
M and M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Mol Med. 2005 Feb;15(2):359-63.
WNT signals are transduced to the beta-catenin pathway or the planar cell polarity (PCP) pathway. Drosophila Frizzled (Fz), Starry night (Stan), Van Gogh (Vang), Prickle (Pk) and Diego (Dgo) are PCP signaling molecules. Human FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9 and FZD10 are Fz homologs. Human CELSR1, CELSR2 and CELSR3 are Stan homologs. Human VANGL1 and VANGL2 are Vang homologs. Human PRICKLE1 and PRICKLE2 are Pk homologs. Human ANKRN6 is a Dgo homolog. Here, we identified and characterized rat Ankrd6 gene by using bioinformatics. Ankrd6 gene, consisting of 15 exons, was located within AC105547.5 genome sequence derived from rat chromosome 5q21. Rat Ankrd6 mRNA was expressed in corpus-striatum, eye, lung, and kidney. Rat Ankrd6 (714 aa) with six ankyrin (Ank) repeats and two coiled-coil regions showed 95.0, 84.2 and 53.4% total-amino-acid identity with mouse, human and zebrafish orthologs, respectively. Ser 340 of rat Ankrd6, conserved among mammalian Ankrd6 orthologs, was a protein kinase A (PKA) phosphotylation and 14-3-3 interaction site. Ank repeats are putative binding domains for Prickle1, Prickle2, Vangl1, and Vangl2. Central coiled-coil region is located within binding domain for Casein kinase I epsilon (CkIe). C-terminal coiled-coil region is located within binding domain for Axin1 and Axin2. Fourth to sixth Ank repeats of vertebrate Ankrd6 orthologs (codon 141-239) were highly conserved in Drosophila Dgo; however, two coiled-coil regions of vertebrate Ankrd6 orthologs were absent in Drosophila Dgo. Due to the molecular evolution, functions of vertebrate Ankrd6 orthologs were predicted to partially differ from those of Drosophila Dgo.
WNT信号被转导至β-连环蛋白途径或平面细胞极性(PCP)途径。果蝇的卷曲蛋白(Frizzled,Fz)、星夜蛋白(Starry night,Stan)、梵高蛋白(Van Gogh,Vang)、刺蛋白(Prickle,Pk)和迭戈蛋白(Diego,Dgo)是PCP信号分子。人类的FZD1、FZD2、FZD3、FZD4、FZD5、FZD6、FZD7、FZD8、FZD9和FZD10是Fz的同源物。人类的CELSR1、CELSR2和CELSR3是Stan的同源物。人类的VANGL1和VANGL2是Vang的同源物。人类的PRICKLE1和PRICKLE2是Pk的同源物。人类的ANKRN6是Dgo的同源物。在此,我们通过生物信息学方法鉴定并表征了大鼠的Ankrd6基因。Ankrd6基因由15个外显子组成,位于源自大鼠5号染色体5q21的AC105547.5基因组序列内。大鼠Ankrd6 mRNA在纹状体、眼睛、肺和肾脏中表达。具有六个锚蛋白(Ank)重复序列和两个卷曲螺旋区域的大鼠Ankrd6(714个氨基酸)与小鼠、人类和斑马鱼的直系同源物的总氨基酸同一性分别为95.0%、84.2%和53.4%。大鼠Ankrd6的第340位丝氨酸在哺乳动物Ankrd6直系同源物中保守,是蛋白激酶A(PKA)磷酸化和14-3-3相互作用位点。Ank重复序列是与Prickle1、Prickle2、Vangl1和Vangl2的假定结合结构域。中央卷曲螺旋区域位于酪蛋白激酶Iε(CkIe)的结合结构域内。C末端卷曲螺旋区域位于Axin1和Axin2的结合结构域内。脊椎动物Ankrd6直系同源物的第四至第六个Ank重复序列(密码子第141 - 239位)在果蝇Dgo中高度保守;然而,脊椎动物Ankrd6直系同源物的两个卷曲螺旋区域在果蝇Dgo中不存在。由于分子进化,预计脊椎动物Ankrd6直系同源物的功能与果蝇Dgo的功能部分不同。