Lin F, Blake D L, Callebaut I, Skerjanc I S, Holmer L, McBurney M W, Paulin-Levasseur M, Worman H J
Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Biol Chem. 2000 Feb 18;275(7):4840-7. doi: 10.1074/jbc.275.7.4840.
The "MAN antigens" are polypeptides recognized by autoantibodies from a patient with a collagen vascular disease and localized to the nuclear envelope. We now show that one of the human MAN antigens termed MAN1 is a 82.3-kDa protein with an amino-terminal domain followed by two hydrophobic segments and a carboxyl-terminal tail. The MAN1 gene contains seven protein-coding exons and is assigned to human chromosome 12q14. Its mRNA is approximately 5.5 kilobases and is detected in several different cell types that were examined. Cell extraction experiments show that MAN1 is an integral membrane protein. When expressed in transfected cells, MAN1 is exclusively targeted to the nuclear envelope, consistent with an inner nuclear membrane localization. Protein sequence analysis reveals that MAN1 shares a conserved globular domain of approximately 40 amino acids, which we term the LEM module, with inner nuclear membrane proteins lamina-associated polypeptide 2 and emerin. The LEM module is also present in two proteins of Caenorhabditis elegans. These results show that MAN1 is an integral protein of the inner nuclear membrane that shares the LEM module with other proteins of this subcellular localization.
“MAN抗原”是一种由胶原血管病患者的自身抗体识别的多肽，定位于核膜。我们现在发现，一种名为MAN1的人类MAN抗原是一种82.3 kDa的蛋白质，其氨基末端结构域后接两个疏水片段和一个羧基末端尾巴。MAN1基因包含7个蛋白质编码外显子，定位于人类染色体12q14。其mRNA约为5.5千碱基，在检测的几种不同细胞类型中均有检测到。细胞提取实验表明，MAN1是一种整合膜蛋白。当在转染细胞中表达时，MAN1专门定位于核膜，与内核膜定位一致。蛋白质序列分析显示，MAN1与内核膜蛋白核纤层相关多肽2和emerin共享一个约40个氨基酸的保守球状结构域，我们将其称为LEM模块。LEM模块也存在于秀丽隐杆线虫的两种蛋白质中。这些结果表明，MAN1是内核膜的一种整合蛋白，与该亚细胞定位的其他蛋白质共享LEM模块。
