Katoh Yuriko, Katoh Masaru
M&M Medical BioInformatics, Hongo 113-0033, Japan.
Int J Oncol. 2005 Aug;27(2):581-5.
Bone morphogenetic proteins (BMPs) are implicated in cell-fate determination of embryonic stem (ES) cells and cancer cells. GREM1 (CKTSF1B1 or DAND2) and CER1 (Cerberus 1 or DAND4) are cysteine knot superfamily proteins, functioning as secreted-type BMP antagonists. BMP4 is preferentially expressed in diffuse-type gastric cancer cells. Here, vertebrate BMP4 orthologs were identified and characterized by using bioinformatics for comparative proteomics and comparative genomics analyses. Baboon BMP4 gene within AC153751.2 genome sequence encoded a 408-aa protein, showing A152V and S298P amino-acid substitutions compared with human BMP4. Cow Bmp4, bat Bmp4 and zebrafish bmp4 genes were located within AC149774.2, AC156788.2 and CR391996.2 genome sequences, respectively. Human BMP4 showed 99.5%, 98.0%, 97.8%, 97.1%, 96.3%, 83.3% and 71.1% total-amino-acid identity with baboon BMP4, cow Bmp4, bat Bmp4, mouse Bmp4, rat Bmp4, chicken bmp4 and zebrafish bmp4, respectively. Human BMP4 gene was found consisting of six exons, including novel exon 1C, and known exons 1 (1A or I), 1B (II), 2 (III), 3 (IV) and 4 (V). Forty human BMP4 ESTs started from exon 1, seven from intron 1 (5'-flanking region of exon 2), and two from exon 1C. Fourteen mouse Bmp4 ESTs started from exon 1, and one from intron 1. The 5'-flanking region of exon 1 and exon 1 itself, but not exons 1C and 1B, were well conserved between human BMP4 and rodent Bmp4 genes. The major promoter region of human BMP4 and rodent Bmp4 genes were located within the 5'-flanking region of exon 1. FOXA2, OLF1, and MYC-binding sites were conserved among the major promoter region of human, baboon, cow, bat, mouse and rat BMP4 orthologs.
骨形态发生蛋白（BMPs）与胚胎干细胞（ES细胞）和癌细胞的细胞命运决定有关。GREM1（CKTSF1B1或DAND2）和CER1（Cerberus 1或DAND4）是半胱氨酸结超家族蛋白，作为分泌型BMP拮抗剂发挥作用。BMP4在弥漫型胃癌细胞中优先表达。在此，通过使用生物信息学进行比较蛋白质组学和比较基因组学分析，鉴定并表征了脊椎动物BMP4直系同源物。AC153751.2基因组序列中的狒狒BMP4基因编码一种408个氨基酸的蛋白质，与人类BMP4相比，显示出A152V和S298P氨基酸取代。牛Bmp4、蝙蝠Bmp4和斑马鱼bmp4基因分别位于AC149774.2、AC156788.2和CR391996.2基因组序列中。人类BMP4与狒狒BMP4、牛Bmp4、蝙蝠Bmp4、小鼠Bmp4、大鼠Bmp4、鸡bmp4和斑马鱼bmp4的总氨基酸同一性分别为99.5%、98.0%、97.8%、97.1%、96.3%、83.3%和71.1%。发现人类BMP4基因由六个外显子组成，包括新的外显子1C，以及已知的外显子1（1A或I）、1B（II）、2（III）、3（IV）和4（V）。40个人类BMP4 ESTs从外显子1开始，7个从内含子1（外显子2的5'侧翼区域）开始，2个从外显子1C开始。14个小鼠Bmp4 ESTs从外显子1开始，1个从内含子1开始。外显子1的5'侧翼区域和外显子1本身，而非外显子1C和1B，在人类BMP4和啮齿动物Bmp4基因之间高度保守。人类BMP4和啮齿动物Bmp4基因的主要启动子区域位于外显子1的5'侧翼区域。FOXA2、OLF1和MYC结合位点在人类、狒狒、牛、蝙蝠、小鼠和大鼠BMP直系同源物的主要启动子区域中保守。
