GENE SEQUENCE OF GALACTOSYLTRANSFERASE MODIFIER PROTEIN ALPHA-LACTALBUMIN AND WP

半乳糖基转移酶修饰蛋白α-乳清蛋白和WP的基因序列

• 批准号: 4691817
• 负责人: P K QASBA
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4691817
• 关键词: DNA; bacterial virus; complementary DNA; cortisol; galactosyltransferases; genetic library; genetic mapping; genome; liver; lysozyme; mammary gland; molecular cloning; nucleic acid sequence; progesterone; structural genes

(A) Alpha-lactalbumin (alpha-LA)-like proteins modify the activity of N-acetyl-glucosaminide beta 1-4 galactosyltransferase and their expression is regulated by hormones. We have isolated and sequenced entire mammary gland alpha-LA gene, including its 5'-flanking sequences. The gene sequences were compared with chicken lysozome gene, since it was proposed that the two genes have arisen from a common ancestral gene. These studies show: 1) alpha-LA and lysozome genes contain 3 introns at similar positions. The first three exons show high nucleotide homologies; 2) 5'-flanking sequence of alpha-LA gene has several identical short repeat sequences. Some of these sequences resemble the concensus sequences which bind hydrocortisone and progesterone receptors which modulate the expression of this gene; and 3) the fourth exon of alpha-LA, which partly codes for the C-terminal residues of the protein, essential for its interaction with galactosyltransferase, is markedly different from the corresponding exon of lysozome gene and is preceded by two (TG) repeats-(TG)21 and (TG)24. It is suggested that the 4th exon of alpha-LA coding for a new functional unit might have replaced the DNA region of primordial lysozome gene and led to a protein with a new function. (B) Rat whey phosphoprotein (Wp) has a double domain structure with striking homologies to a protease inhibitor. Wp-gene expression is regulated by the same set of hormones as the alpha-LA gene. Rat Wp-gene has been isolated and its full sequence is nearing completion. The gene structure and nucleotide sequences show that: a) there are three intervening sequences in the entire gene which is 2.5 kb in length; b) second and third exons code for first and second domains of the protein, respectively; and c) first and the third intervening sequences encompassing the second and third exons, have several repeat and inverted repeat sequences.

(A)α-乳白蛋白（α-LA）样蛋白质修饰 N-乙酰氨基葡萄糖苷β 1-4半乳糖基转移酶及其表达 是由荷尔蒙调节的 我们已经分离并测序了整个乳腺 腺α-LA基因，包括其5 '侧翼序列。 基因 序列与鸡溶菌酶基因进行了比较， 这两个基因来自一个共同的祖先基因。 这些研究 显示：1）α-LA和溶虫体基因含有3个内含子， 岗位 前三个外显子显示高核苷酸同源性; 2） α-LA基因的5 ′侧翼序列有几个相同的短重复序列 序列的 其中一些序列类似于 结合氢化可的松和孕酮受体， 该基因的表达;和3）α-LA的第四外显子，其部分 编码蛋白质的C-末端残基，对于其 与半乳糖基转移酶的相互作用，明显不同于 溶酶体基因的相应外显子，前面有两个（TG） 重复序列-（TG）21和（TG）24。 提示α-LA基因第4外显子可能与α-LA基因的转录调控有关。 编码一个新的功能单位可能已经取代了 原始溶菌酶基因，并导致一个新的功能的蛋白质。 (B)大鼠 乳清磷蛋白（Wp）具有双结构域结构， 与蛋白酶抑制剂同源。 Wp基因的表达是由 与α-LA基因相同的激素 大鼠Wp基因已被分离 它的全部序列即将完成 基因结构和 核苷酸序列显示：a）存在三个间插序列 整个基因长度为2.5 kb; B）第二和第三外显子 分别编码所述蛋白质的第一和第二结构域;以及 第一和第三间插序列，所述第一和第三间插序列包围第二和第三间插序列， 外显子，有几个重复和反向重复序列。