Marquet S, Lepage P, Hudson T J, Musser J M, Schurr E
McGill Centre for the Study of Host Resistance, McGill University Health Centre, Montreal, Quebec, Canada.
Mamm Genome. 2000 Sep;11(9):755-62. doi: 10.1007/s003350010151.
Several lines of independent evidence suggest that human Natural Resistance Associated Macrophage Protein 1 gene (NRAMP1) is an important regulator of susceptibility to infectious diseases caused by certain intracellular pathogens. Here, we report the nucleotide sequence of 32198 bp of genomic DNA overlapping NRAMP1 on chromosomal region 2q35. The NRAMP1 gene spans 13604 bp. The gene and its 5' genomic region are highly enriched for DNA repeat sequences. A second gene was identified in the immediate vicinity of NRAMP1 and was tentatively named Nuclear LIM Interactor-Interacting Factor (NLI-IF) by analogy to its closest ortholog. The human NLI-IF gene begins 4721 bp downstream of the NRAMP1 stop codon and is composed of seven exons varying in size from 57 bp to 1644 bp. The gene gives rise to a 2655-bp mRNA transcript that contains a 783-bp open reading frame. The predicted molecular weight of the 261-amino acid NLI-IF protein is 29.2 kDa. Several putative gene regulatory elements were identified in the 5' upstream region of NLI-IF, including consensus binding sequences for Sp1, AP-2, NF-kappa B, and PU 1. The NLI-IF amino acid sequence has homology to proteins that have a high degree of homology with the NLI-interacting factor from Gallus gallus and are found in divergent species ranging from yeast to plants. NLI-IF is part of a human gene family encoding four related proteins of unknown function. Northern blot analysis of 15 different human tissues revealed a 2.6-kb NLI-IF mRNA that was ubiquitously expressed, but at varying levels. A second transcript with estimated size of 7 kb was expressed only in the placenta. Our data provide new sequence information about the NRAMP1 gene region that will be useful in the search for genetic variants causally involved in altered susceptibility to infectious diseases.
多条独立证据表明，人类自然抗性相关巨噬细胞蛋白1基因（NRAMP1）是对某些细胞内病原体引起的传染病易感性的重要调节因子。在此，我们报告了位于染色体2q35区域与NRAMP1重叠的32198 bp基因组DNA的核苷酸序列。NRAMP1基因跨度为13604 bp。该基因及其5'基因组区域富含DNA重复序列。在NRAMP1紧邻区域鉴定出第二个基因，并根据其最接近的直系同源物暂时命名为核LIM相互作用因子相互作用因子（NLI-IF）。人类NLI-IF基因在NRAMP1终止密码子下游4721 bp处起始，由七个外显子组成，大小从57 bp到1644 bp不等。该基因产生一个2655 bp的mRNA转录本，其中包含一个783 bp的开放阅读框。预测的261个氨基酸的NLI-IF蛋白的分子量为29.2 kDa。在NLI-IF的5'上游区域鉴定出几个推定的基因调控元件，包括Sp1、AP-2、NF-κB和PU 1的共有结合序列。NLI-IF氨基酸序列与与家鸡NLI相互作用因子具有高度同源性且存在于从酵母到植物等不同物种中的蛋白质具有同源性。NLI-IF是一个人类基因家族的一部分，该家族编码四种功能未知的相关蛋白。对15种不同人类组织的Northern印迹分析显示，存在一个2.6 kb的NLI-IF mRNA普遍表达，但水平各异。另一个估计大小为7 kb的转录本仅在胎盘中表达。我们的数据提供了关于NRAMP1基因区域的新序列信息，这将有助于寻找与传染病易感性改变因果相关的遗传变异。
