人类胃（H⁺ + K⁺）-ATP酶基因。在外显子/内含子组织上与（Na⁺ + K⁺）-ATP酶基因相似，但在调控区域存在差异。

Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes in exon/intron organization but difference in control region.

作者信息

Maeda M, Oshiman K, Tamura S, Futai M

机构信息

Department of Organic Chemistry and Biochemistry, Osaka University, Japan.

出版信息

J Biol Chem. 1990 Jun 5;265(16):9027-32.

PMID:2160952

Abstract

The human gastric (H+ + K+)-ATPase gene (15 kilobases) was cloned, and its nucleotide sequence was determined. The gene has 22 exons and codes a protein of 1,035 residues including the initiator methionine (Mr = 114,047). A conserved lysine-rich sequence with inserted glycine residues was found near the amino terminus of the enzyme. The phosphorylation site and pyridoxal 5'-phosphate- and fluorescein isothiocyanate-binding residues found in the rat and pig enzymes are also conserved in the human enzyme. The positions of introns in the human (H+ + K+)-ATPase gene are essentially the same as those in the human (Na+ + K+)-ATPase alpha and alpha III subunits; but the first introns of the two enzymes are difficult to align, and unlike in the (Na+ + K+)-ATPase gene, the sixth exon in the (H+ + K+)-ATPase gene is not separated by an intron. Furthermore, the ninth intron is located two bases upstream of the position for the corresponding intron of the (Na+ + K+)-ATPase alpha III subunit. The similarity in organization of these two ATPase genes and the homology in the primary structures of their proteins (approximately 60%) suggest that these two genes were derived from a common ancestral gene. However, the 5'-flanking regions of the genes for (H+ + K+)-ATPase and the (Na+ + K+)-ATPase alpha (+) subunit show no apparent sequence homology, indicating that their transcriptions are regulated differently. The control region of the fast-twitch sarcoplasmic reticulum Ca2(+)-ATPase gene also showed no sequence homology to that of (H+ + K+)-ATPase. The 5'-flanking region of the (H+ + K+)-ATPase gene contains potential binding sites for RNA polymerase II and various transcriptional regulation factors and several direct and inverted repeat sequences which may be important for specific and controlled expression of the gene in gastric parietal cells. There are two polyadenylation signals in the 3'-flanking region of the (H+ + K+)-ATPase gene, but the sequence of this region shows no homology to those of the corresponding regions of the genes for the (Na+ + K+)-ATPase alpha and alpha III subunits.

摘要

克隆了人类胃（H⁺+K⁺）-ATP酶基因（15千碱基），并测定了其核苷酸序列。该基因有22个外显子，编码一个含起始甲硫氨酸（Mr = 114,047）的1035个残基的蛋白质。在该酶的氨基末端附近发现了一个带有插入甘氨酸残基的保守的富含赖氨酸的序列。在大鼠和猪的酶中发现的磷酸化位点以及与磷酸吡哆醛和异硫氰酸荧光素结合的残基在人类酶中也保守。人类（H⁺+K⁺）-ATP酶基因中内含子的位置与人类（Na⁺+K⁺）-ATP酶α和αIII亚基中的基本相同；但这两种酶的第一个内含子难以比对，并且与（Na⁺+K⁺）-ATP酶基因不同，（H⁺+K⁺）-ATP酶基因中的第六个外显子没有被内含子隔开。此外，第九个内含子位于（Na⁺+K⁺）-ATP酶αIII亚基相应内含子位置上游两个碱基处。这两个ATP酶基因在组织上的相似性以及它们蛋白质一级结构中的同源性（约60%）表明这两个基因源自一个共同的祖先基因。然而，（H⁺+K⁺）-ATP酶基因和（Na⁺+K⁺）-ATP酶α（+）亚基基因的5'侧翼区域没有明显的序列同源性，表明它们的转录调控方式不同。快肌肌浆网Ca²⁺-ATP酶基因的调控区域与（H⁺+K⁺）-ATP酶基因的调控区域也没有序列同源性。（H⁺+K⁺）-ATP酶基因的5'侧翼区域包含RNA聚合酶II和各种转录调控因子的潜在结合位点以及几个正向和反向重复序列，这些序列可能对该基因在胃壁细胞中的特异性和可控表达很重要。（H⁺+K⁺）-ATP酶基因的3'侧翼区域有两个聚腺苷酸化信号，但该区域的序列与（Na⁺+K⁺）-ATP酶α和αIII亚基基因相应区域的序列没有同源性。