HUMAN MYELOID PLASMA-MEMBRANE GLYCOPROTEIN CD13 (GP150) IS IDENTICAL TO AMINOPEPTIDASE-N

HUMAN MYELOID PLASMA-MEMBRANE GLYCOPROTEIN CD13 (GP150) IS IDENTICAL TO AMINOPEPTIDASE-N
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DOI:
10.1172/jci114015
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发表时间:
1989-04-01
影响因子:
15.9
通讯作者:
PEIPER, SC
PEIPER, SC
中科院分区:
医学1区
文献类型:
--
作者:
LOOK, AT;ASHMUN, RA;PEIPER, SC

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为了确定 CD13(一种最初在正常和恶性人骨髓细胞亚群中鉴定的 150 kD 细胞表面糖蛋白)的一级结构,我们在重叠的互补 DNA (cDNA) 克隆中分离了编码该多肽的完整序列。我们的 cDNA 克隆的真实性通过亚克隆到逆转录病毒表达载体中的编码序列在转染的小鼠成纤维细胞表面介导真正的 CD13 分子表达的能力得到了证明。核苷酸序列预测膜蛋白由 967 个氨基酸组成,在氨基末端附近有一个 24 个氨基酸的疏水片段。 CD13分子的氨基末端蛋白质序列分析表明疏水性片段没有被切割,而是既充当膜插入的信号又充当稳定的跨膜片段。该分子的其余部分由一个大的胞外羧基末端结构域组成,其中包含锌结合金属蛋白酶超家族成员特征的五肽共有序列。与此类已知酶的序列比较表明,CD13 与氨肽酶 N 相同,氨肽酶 N 是一种膜结合糖蛋白,被认为参与多种细胞类型调节肽的代谢,包括小肠和肾小管上皮细胞、巨噬细胞、粒细胞和中枢神经系统细胞制备的突触膜。
To determine the primary structure of CD13, a 150-kD cell surface glycoprotein originally identified on subsets on normal and malignant human myeloid cells, we isolated the complete sequences encoding the polypeptide in overlapping complementary DNA (cDNA) clones. The authenticity of our cDNA clones was demonstrated by the ability of the coding sequences, subcloned in a retroviral expression vector, to mediate expression of bona fide CD13 molecules at the surface of transfected mouse fibroblasts. The nucleotide sequence predicts a 967 amino acid integral membrane protein with a single, 24 amino acid hydrophobic segment near the amino terminus. Amino-terminal protein sequence analysis of CD13 molecules indicated that the hydrophobic segment is not cleaved, but rather serves as both a signal for membrane insertion and as a stable membrane-spanning segment. The remainder of the molecule consists of a large extracellular carboxyterminal domain, which contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloprotease superfamily. Sequence comparisons with known enzymes of this class revealed that CD13 is identical to aminopeptidase N, a membrane-bound glycoprotein thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes prepared from cells of the central nervous system.