SLC2A9, A Candidate ER GLUT in Normal and Cancer Cells

描述：（从申请人的描述扫描）葡萄糖是 正常和恶性组织的优选能量基质。足够 循环水平通过饮食摄入、糖原分解和 肝脏和肾脏的再生。几种质膜葡萄糖 已经描述了转运蛋白，然而微粒体葡萄糖 转运蛋白，这可能是需要运输葡萄糖从 内质网在糖原分解和糖原生成的最后一步， 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cDNA的家族（HGMW批准的符号是SLC 2A 9 （GLUT 9），GenBank登录号AF 210317）。该cDNA编码一种蛋白质， 540个氨基酸的长度，并具有12个推定的跨膜结构域。的 预测的蛋白质序列分别有44%和38%的序列同一性， 分别为Glut 5和Glut 1。该cDNA主要在人肝脏中表达 和肾脏，并具有可能的NH 2末端内质网靶向 母题它也在人类结肠癌和软组织肉瘤中表达。我们 假设SLC 2A 9是内质网（ER）葡萄糖转运蛋白 (also称为T3），与微粒体葡萄糖-6-磷酸酶相关 （G6）复合物。因此，我们将： 证明SLC 2A 9在正常和恶性肿瘤中的亚细胞定位 细胞 通过在非洲爪蟾卵母细胞中表达确定SLC 2A 9的功能 系统和 评价SLC 2A 9敲除小鼠的表型和生化特征。如果 SLC 2A 9是G6 β系统的内质网葡萄糖转运蛋白，我们预测， 无效小鼠将表现出糖原累积病（GSD）的特征， 在G6 β（-/-）小鼠中报告。 SLC 2A 9作为内质网葡萄糖转运蛋白的鉴定将 提高对GSD和良性和 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.