Maruyama K, Tsukada T, Honda M, Nara-Ashizawa N, Noguchi K, Cheng J, Ohkura N, Sasaki K, Yamaguchi K
Growth Factor Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan.
Mol Cell Endocrinol. 2000 Oct 25;168(1-2):135-40. doi: 10.1016/s0303-7207(00)00307-5.
Menin is a protein product of a tumor supressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome. We determined the nucleotide sequence of the Drosophila menin cDNA using RT-PCR and RACE, and confirmed it by direct sequencing of genomic DNA. Gene expression of Drosophila menin was detected by Northern blot analysis in adult and embryo as two types of transcripts, one identical in size to the cDNA, and the other larger but detected only in embryo. The Drosophila menin gene was composed of five exons in which the protein was encoded in exon 2 through 5, and spanned approximately 6.3 kb. The deduced amino acid (AA) sequence of Drosophila menin consisted of 751 AAs with a calculated molecular mass of 81.7 kDa, and showed 44-47% identity to human, rat, mouse and zebrafish menin over the entire length. Among the AA residue substitutions that have been reported as disease-associated missense mutations and single AA deletions, 53 out of 71 were completely conserved in Drosophila. The presence of menin ortholog in insect indicates that menin is an evolutionally conserved protein with a fundamental role in biological processes.
Menin是肿瘤抑制基因MEN1的蛋白质产物，该基因的突变会导致1型多发性内分泌肿瘤，这是一种常染色体显性遗传家族性癌症综合征。我们使用逆转录聚合酶链反应（RT-PCR）和cDNA末端快速扩增技术（RACE）测定了果蝇Menin cDNA的核苷酸序列，并通过对基因组DNA的直接测序进行了确认。通过Northern印迹分析在成年果蝇和胚胎中检测到果蝇Menin的基因表达，有两种转录本，一种大小与cDNA相同，另一种较大，但仅在胚胎中检测到。果蝇Menin基因由五个外显子组成，其中蛋白质在外显子2至5中编码，跨度约为6.3 kb。果蝇Menin推导的氨基酸（AA）序列由751个氨基酸组成，计算分子量为81.7 kDa，在全长上与人类、大鼠、小鼠和斑马鱼的Menin具有44-47%的同一性。在已报道的与疾病相关的错义突变和单个氨基酸缺失的氨基酸残基取代中，71个中有53个在果蝇中完全保守。昆虫中Menin直系同源物的存在表明Menin是一种在生物过程中具有基本作用的进化保守蛋白。
