SLC2A9, A Candidate ER GLUT in Normal and Cancer Cells

描述：(根据申请者的描述扫描)葡萄糖是 正常组织和恶性组织的首选能量底物。足够 循环水平是通过饮食摄入、糖原分解和 肝脏和肾脏中的糖异生。几种质膜葡萄糖 已经描述了转运蛋白，然而微体葡萄糖 转运蛋白，这可能是运输葡萄糖所必需的 糖原分解和糖异生的最后一步中的内质网， 一直没有找到。我们克隆了人类葡萄糖转运蛋白的一个新成员 来自人肉瘤和肾脏的家族基因(HGMW批准的代号为SLC2A9 (GLUT9)，GenBank登录号：AF210317)。这种cDNA编码一种蛋白质，这种蛋白质是 该基因全长540个氨基酸，有12个跨膜结构域。这个 预测的蛋白质序列与44%和38%的序列同源性 分别为过剩5和过剩1。该基因主要在人的肝脏中表达。 和肾脏，并可能具有NH2末端内质网靶向 Motif。它也在人类结肠癌和软组织肉瘤中表达。我们 假设SLC2A9是内质网葡萄糖转运体 (也称为T3)，与微粒体葡萄糖-6-磷酸酶有关 (G6Pase)复合体。因此，我们会： SLC2A9在正常和恶性肿瘤中的亚细胞定位 细胞。 通过在非洲爪哇卵母细胞中的表达确定SLC2A9的功能 系统，以及 评估SLC2A9基因缺失小鼠的表型和生化特征。如果 SLC2A9是G6Pase系统的内质网葡萄糖转运体，我们预测 Null小鼠将表现出糖原储存疾病(GSD)的特征，如 在G6Pase(-/-)小鼠中报告。 内质网葡萄糖转运蛋白SLC2A9的鉴定 提高对GSD的认识，以及对良性和非典型肺炎患者的糖代谢的了解 恶性组织。

DESCRIPTION: (Scanned from the applicant's description) Glucose is the preferred energy substrate of normal and malignant tissues. Adequate circulating levels are maintained by dietary intake, glycogenolysis and gluconeogenesis in the liver and kidney. Several plasma membrane glucose transporter proteins have been described, however a microsomal glucose transporter, which may be required for transport of glucose from the endoplasmic reticulum in the final step of glycogenolysis and gluconeogenesis, has not been found. We cloned a novel member of the human glucose transporter family from human sarcoma and kidney cDNA (HGMW-approved symbol is SLC2A9 (GLUT9), GenBank accession No. AF210317). This cDNA encodes a protein that is 540 amino acids in length, and has 12 putative membrane-spanning domains. The predicted protein sequence has 44 percent and 38 percent sequence identity to Glut 5 and Glut 1, respectively. The cDNA is expressed primarily in human liver and kidney, and has a possible NH2 terminal endoplasmic reticulum targeting motif. It is also expressed in human colon cancer and soft tissue sarcomas. We hypothesize that SLC2A9 is the endoplasmic reticulum (ER) glucose transporter (also called T3) which is associated with the microsomal Glucose-6-phosphatase (G6Pase) complex. Accordingly, we will: Demonstrate the sub-cellular localization of SLC2A9 in normal and malignant cells. Determine the function of SLC2A9 by expression in a Xenopus oocyte expression system, and Evaluate the phenotypic and biochemical features of an SLC2A9 null mouse. If SLC2A9 is the ER glucose transporter of the G6Pase system, we predict that the null mouse will demonstrate features of glycogen storage disease (GSD), as reported in the G6Pase (-/-) mouse. Identification of SLC2A9 as the endoplasmic reticulum glucose transporter will improve understanding of GSDs, and of glucose metabolism in benign and malignant tissues.