Ly-6和uPAR（LU）结构域蛋白是一个大型的细胞表面标志物家族。特别是，小鼠Ly-6A/Sca-1广泛应用于各种干细胞的标志物，然而它的人类同源基因缺失。本研究基于小鼠和人类LU结构域蛋白的系统调查和比较基因组研究，鉴定了一个之前未注释的人类基因，编码小鼠Ly-6A/Sca-1的候选同源基因。该基因被命名为LY6A，在大多数外显子序列上与lncRNA基因反向重叠。我们发现LY6A在垂体肿瘤中异常表达，但在正常垂体组织中没有表达，并可能参与肿瘤发生。类似于小鼠Ly-6A/Sca-1，人类LY6A也被干扰素上调，表明人类和小鼠之间存在保守的转录调控机制。我们克隆了全长的LY6A cDNA，其编码的蛋白序列、结构域和外显子-内含子结构与小鼠Ly-6A/Sca-1都很相似。在细胞中异位表达LY6A蛋白，证明它在处理和磷脂酰肌醇锚定到细胞膜方面与小鼠Ly-6A/Sca-1表现一致。总之，这些研究揭示了一个编码候选生物标志物的新人类基因，并提供了一个有趣的模型基因，用于研究基因调控和进化机制。© 2022. 高等教育出版社。

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.© 2022. Higher Education Press.