Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B.

Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B.
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DOI:
10.1083/jcb.122.1.265
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发表时间:
1993-07
影响因子:
7.8
通讯作者:
Miller, W L
Miller, W L
中科院分区:
生物学1区
文献类型:
--
作者:
Bristow, J;Tee, M K;Gitelman, S E;Mellon, S H;Miller, W L

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一种名为XB的人类基因与编码类固醇21-羟基酶的P450c21B基因重叠,并编码一种与细胞外基质蛋白非常相似的蛋白质。对噬菌体、粘粒克隆和cDNA片段的测序表明,XB基因全长65kb,由39个外显子组成,编码一个12kb的mRNA。预测的400kD以上的蛋白质由5个不同的结构域组成:信号肽、包含3个七肽重复序列的疏水结构域、一系列18.5个EGF样重复序列、29个纤维连接蛋白III型重复序列和一个羧基末端纤维蛋白原样结构域。由于XB基因编码的蛋白质的结构与Tenascin非常相似,我们将其命名为Tn-X,并提出了一种简化的Tenascins家族命名系统。核糖核酸酶保护实验表明,TN-X转录本在人胎儿组织中普遍表达,其中以胎儿睾丸、胎儿骨骼肌、心肌和平滑肌表达最高。两个肾上腺特异的转录本,P450c21B(类固醇21-羟基酶)和Y(未翻译的转录本)与DNA互补链上的XB基因重叠,产生了一系列独特的重叠转录本:一个“多基因”。原位杂交组织化学实验表明,TN-X转录本和互补DNA链上编码的P450c21和Y转录本均在人肾上腺皮质的同一细胞中表达。遗传数据表明,TN-X可能是生命所必需的。
A human gene termed XB overlaps the P450c21B gene encoding steroid 21- hydroxylase and encodes a protein that closely resembles extracellular matrix proteins. Sequencing of phage and cosmid clones and of cDNA fragments shows that the XB gene spans 65 kb of DNA, consisting of 39 exons that encode a 12-kb mRNA. The predicted protein of over 400 kD consists of five distinct domains: a signal peptide, a hydrophobic domain containing three heptad repeats, a series of 18.5 EGF-like repeats, 29 fibronectin type III repeats, and a carboxy-terminal fibrinogen-like domain. Because the structure of the protein encoded by the XB gene closely resembles tenascin, we term this protein tenascin-X (TN-X), and propose a simplified nomenclature system for the family of tenascins. RNase protection experiments show that the TN-X transcript is expressed ubiquitously in human fetal tissues, with the greatest expression in the fetal testis and in fetal skeletal, cardiac, and smooth muscle. Two adrenal-specific transcripts, P450c21B (steroid 21- hydroxylase) and Y (an untranslated transcript) overlap the XB gene on the complementary strand of DNA, yielding a unique array of overlapping transcripts: a "polygene." In situ hybridization histochemistry experiments show that the TN-X transcript and the P450c21 and Y transcripts encoded on the complementary DNA strand are all expressed in the same cells of the human adrenal cortex. Genetic data suggest that TN-X may be essential for life.