HUMAN INTESTINAL H+/PEPTIDE COTRANSPORTER - CLONING, FUNCTIONAL EXPRESSION, AND CHROMOSOMAL LOCALIZATION
HUMAN INTESTINAL H+/PEPTIDE COTRANSPORTER - CLONING, FUNCTIONAL EXPRESSION, AND CHROMOSOMAL LOCALIZATION
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DOI：
10.1074/jbc.270.12.6456
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发表时间：
1995-03-24
影响因子：
4.8
通讯作者：
LEIBACH, FH
中科院分区：
文献类型：
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作者：
RONG, LA;FEI, YJ;LEIBACH, FH
在哺乳动物小肠中，H+偶联肽转运蛋白负责吸收膳食蛋白质消化产生的小肽。最近，已从兔肠 cDNA 文库中分离出编码 H+/肽共转运蛋白的 cDNA 克隆（Fei, Y, J.、Kanai, Y.、Nussberger, S.、Ganapathy, V.、Leibach, F. H.、Romero, M. F.、Singh, S. K.、Boron, W. F. 和 Hediger, M. A. (1994) Nature 368， 563-566）。使用源自兔 H+/肽共转运蛋白 cDNA 的探针筛选人肠道 cDNA 文库，结果鉴定出当在 HeLa 细胞或非洲爪蟾卵母细胞中表达时诱导 H+ 依赖性肽转运活性的 cDNA。预测的蛋白质由 708 个氨基酸组成，具有 12 个跨膜结构域和两个推测的蛋白激酶 C 依赖性磷酸化位点。 cDNA 诱导的转运过程接受二肽、三肽和氨基β-内酰胺抗生素，但不接受游离氨基酸作为底物。人 H+/肽协同转运蛋白与兔 H+/肽协同转运蛋白表现出高度同源性（81% 同一性和 92% 相似性）。但令人惊讶的是，这些转运蛋白与细菌和酵母中存在的 H+ 偶联肽转运蛋白仅表现出微弱的同源性。通过体细胞杂交分析和原位杂交进行的染色体分配研究已将编码克隆人 H+/肽协同转运蛋白的基因定位到 13 号染色体 q33-->q34。
In mammalian small intestine, a H+-coupled peptide transporter is responsible for the absorption of small peptides arising from digestion of dietary proteins. Recently a cDNA clone encoding a H+/peptide cotransporter has been isolated from a rabbit intestinal cDNA library (Fei, Y, J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F. H., Romero, M. F., Singh, S. K., Boron, W. F., and Hediger, M. A. (1994) Nature 368, 563-566). Screening of a human intestinal cDNA library with a probe derived from the rabbit H+/peptide cotransporter cDNA resulted in the identification of a cDNA which when expressed in HeLa cells or in Xenopus laevis oocytes induced H+-dependent peptide transport activity. The predicted protein consists of 708 amino acids with 12 membrane-spanning domains and two putative sites for protein kinase C-dependent phosphorylation. The cDNA-induced transport process accepts dipeptides, tripeptides, and amino beta-lactam antibiotics but not free amino acids as substrates. The human H+/peptide cotransporter exhibits a high degree of homology (81% identity and 92% similarity) to the rabbit H+/peptide cotransporter. But surprisingly these transporters show only a weak homology to the H+-coupled peptide transport proteins present in bacteria and yeast. Chromosomal assignment studies with somatic cell hybrid analysis and in situ hybridization have located the gene encoding the cloned human H+/peptide cotransporter to chromosome 13 q33-->q34.