Katoh Masuko, Katoh Masaru
M&M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Mol Med. 2005 Mar;15(3):533-8.
Frizzled-1 (FZD1), FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9 and FZD10 are seven-transmembrane-type WNT receptors with extracellular Frizzled (Fz) domain. ROR1, ROR2 and MUSK are receptor-type tyrosine kinases with extracellular Fz domain, while MFRP is type II transmembrane protein with extracellular Fz domain. ROR1, ROR2, MUSK and MFRP are predicted to transduce or regulate WNT signaling. Here, we identified and characterized rat Ror1 and Ror2 genes by using bioinformatics. Rat Ror1 gene was located within AC108320.4, AC098031.5 and AC129856.4 genome sequences, while rat Ror2 gene was located within AC139870.3 and AC123431.4 genome sequences. Exon-intron structure was conserved between rat Ror1 and Ror2 genes, consisting of nine exons. Rat Ror1 mRNA was expressed in fetal ventricle, while rat Ror2 mRNA was expressed in cerebral cortex, hypothalamus, dorsolateral prostate, and chondrosarcoma. Rat Ror1 (937 aa) and Ror2 (943 aa) showed 56.5% total-amino-acid identity. Rat Ror1 and Ror2 were type I transmembrane proteins with extracellular Immunoglobulin-like (Ig), Fz, Kringle (KR) domains, and cytoplasmic Juxta-membrane (JM), Tyrosine kinase (TK), and Ror homology C-terminal (RORHC) domains. Casein kinase Iepsilon-binding RORHC domain was conserved among vertebrate Ror1 and Ror2 homologs, but not in Drosophila Ror. Thr 582 within TK domain was conserved among mammalian Ror family members, and was predicted as Casein kinase I phosphorylation site. This is the first report on rat Ror1 and Ror2 genes as well as on molecular evolution of Ror1 and Ror2 homologs.
卷曲蛋白-1(FZD1)、FZD2、FZD3、FZD4、FZD5、FZD6、FZD7、FZD8、FZD9和FZD10是具有细胞外卷曲蛋白(Fz)结构域的七跨膜型WNT受体。ROR1、ROR2和MUSK是具有细胞外Fz结构域的受体型酪氨酸激酶,而MFRP是具有细胞外Fz结构域的II型跨膜蛋白。预计ROR1、ROR2、MUSK和MFRP可转导或调节WNT信号传导。在此,我们通过生物信息学鉴定并表征了大鼠Ror1和Ror2基因。大鼠Ror1基因位于AC108320.4、AC098031.5和AC129856.4基因组序列内,而大鼠Ror2基因位于AC139870.3和AC123431.4基因组序列内。大鼠Ror1和Ror2基因之间的外显子-内含子结构保守,由九个外显子组成。大鼠Ror1 mRNA在胎儿心室中表达,而大鼠Ror2 mRNA在大脑皮层、下丘脑、背外侧前列腺和软骨肉瘤中表达。大鼠Ror1(937个氨基酸)和Ror2(943个氨基酸)的总氨基酸同一性为56.5%。大鼠Ror1和Ror2是I型跨膜蛋白,具有细胞外免疫球蛋白样(Ig)、Fz、kringle(KR)结构域,以及细胞质近膜(JM)、酪氨酸激酶(TK)和Ror同源C末端(RORHC)结构域。酪蛋白激酶Iε结合RORHC结构域在脊椎动物Ror1和Ror2同源物中保守,但在果蝇Ror中不保守。TK结构域内的苏氨酸582在哺乳动物Ror家族成员中保守,并被预测为酪蛋白激酶I磷酸化位点。这是关于大鼠Ror1和Ror2基因以及Ror1和Ror2同源物分子进化的首次报道。