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人DAAM2基因的电子克隆及特征分析

Identification and characterization of human DAAM2 gene in silico.

作者信息

Katoh Masuko, Katoh Masaru

机构信息

M&M Medical BioInformatics, Narashino 275-0022, Japan.

出版信息

Int J Oncol. 2003 Apr;22(4):915-20.

Abstract

WNT signals play key roles in carcinogenesis and embryogenesis through the specification of cell fate and polarity. Dishevelled proteins are implicated in the WNT - beta-catenin pathway and the WNT-PCP pathway. DAAM1/KIAA0666 is a Dishevelled-binding protein transducing WNT signals to the PCP pathway. Here, we identified and characterized DAAM2 gene by using bioinformatics. Uncharacterized FLJ34430 and KIAA0381 cDNAs were homologous to DAAM1. FLJ34430 was recombined with URB (XM_087331) in the 3'-region, and KIAA0381 was truncated in the 5'-region. Nucleotide sequence of DAAM2 cDNA was determined in silico by adding nucleotide position 1-793 of FLJ34430 onto the 5'-end of KIAA0381. DAAM2 gene consists of 27 exons, and gives rise to four splicing variants due to alternative splicing of alternative promoter type as well as of cassette exon type. DAAM2 gene was linked to the MOCS1 gene on human chromosome 6p21.3 with an interval less than 1 kb. DAAM2 mRNA was expressed in fetal heart, adult hypothalamus, eye, spinal cord, lung, prostate, kidney, and also in glioblastoma, oligodendroglioma, melanoma, mammary adenocarcinoma and chondrosarcoma. DAAM2 was a 1077-amino-acid protein with Formin-homology FH1 and FH2 domains, which showed 68.9% total-amino-acid identity with DAAM1. Among Formin-homology proteins, FDD (Formin-like, Diaphanous, Daam) domain was conserved in FMNL1/FMNL/KW-13, FMNL2/KIAA1902/FHOD2, DIAPH1, DIAPH2, DAAM1 and DAAM2, but not in Fmn1, Fmn2, FHOD1 and Grid2ip. Therefore, it was concluded that FMNL1, FMNL2, DIAPH1, DIAPH2, DAAM1 and DAAM2 proteins constitute the Formin-homology FDD subfamily.

摘要

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。散乱蛋白与WNT-β-连环蛋白信号通路和WNT-PCP信号通路有关。DAAM1/KIAA0666是一种与散乱蛋白结合的蛋白,可将WNT信号转导至PCP信号通路。在此,我们利用生物信息学鉴定并表征了DAAM2基因。未表征的FLJ34430和KIAA0381 cDNA与DAAM1同源。FLJ34430在3'区域与URB(XM_087331)重组,KIAA0381在5'区域被截短。通过将FLJ34430的核苷酸位置1-793添加到KIAA0381的5'末端,在计算机上确定了DAAM2 cDNA的核苷酸序列。DAAM2基因由27个外显子组成,由于可变启动子类型以及盒式外显子类型的可变剪接,产生了四种剪接变体。DAAM2基因与人类染色体6p21.3上的MOCS1基因相连,间隔小于1 kb。DAAM2 mRNA在胎儿心脏、成人下丘脑、眼睛、脊髓、肺、前列腺、肾脏中表达,在胶质母细胞瘤寡突胶质细胞瘤黑素瘤乳腺腺癌和软骨肉瘤中也有表达DAAM2是一种含有formin同源FH1和FH2结构域的1077个氨基酸蛋白,与DAAM1具有68.9%的总氨基酸同一性在formin同源蛋白中FDD(formin样、透明质酸样、Daam)结构域在FMNL1/FMNL/KW-13、FMNL2/KIAA1902/FHOD2、DIAPH1、DIAPH2 DAAM1和DAAM2中保守,但在Fmn1、Fmn2 FHOD1和Grid2ip中不保守。因此,得出结论,FMNL1、FMNL2、DIAPH1、DIAPH2、DAAM1和DAAM2蛋白构成了formin同源FDD亚家族。

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