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首页> 外文期刊>Biochemistry >Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B).
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Characterization of the gene encoding human TAFI (thrombin-activable fibrinolysis inhibitor; plasma procarboxypeptidase B).

机译：编码人TAFI（凝血酶激活的纤维蛋白溶解抑制剂;血浆原羧肽酶B）的基因的表征。

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摘要

Thrombin-activable fibrinolysis inhibitor (TAFI) is a recently described human plasma zymogen that is related to pancreatic carboxypeptidase B. The active form of TAFI (TAFIa), which is formed by thrombin cleavage of the zymogen, likely inhibits fibrinolysis by removal from partially degraded fibrin of the carboxyl-terminal lysine residues which act to stimulate plasminogen activation. We have isolated and characterized genomic clones which encompass the entire human TAFI gene from lambda phage and bacterial artificial chromosome genomic libraries. The complete TAFI gene contains 11 exons and spans approximately 48 kb of genomic DNA. The positions of intron/exon boundaries are conserved between the TAFI gene and the rat pancreatic carboxypeptidase A1, A2, and B and the human mast cell carboxypeptidase A genes, indicating that these carboxypeptidases arose from a common ancestral gene. However, the intron lengths diverge significantly among all of these genes. The TAFI promoter lacks a consensus TATA sequence, and transcription is initiated from multiple sites. Transient transfection of reporter plasmids containing portions of the TAFI 5'-flanking region into mammalian cells allowed localization of the promoter and identified a approximately 70 bp region crucial for liver-specific transcription. Sequence analysis of cDNA clones obtained from human liver RNA indicated that the TAFI transcript is polyadenylated at three different sites. Our findings will facilitate the assessment of the regulation of TAFI expression by transcriptional and/or posttranscriptional mechanisms. Furthermore, knowledge of the genomic structure of the TAFI gene will aid in the identification of mutations that may be associated with the tendency to either bleed or thrombose.
机译：凝血酶激活的纤维蛋白溶解抑制剂（TAFI）是最近描述的与血浆羧肽酶B相关的人血浆酶原。TAFI（TAFIa）的活性形式是通过凝血酶裂解酶原而形成的，它可能通过去除部分降解的纤维素而抑制纤维蛋白溶解。羧基末端赖氨酸残基的纤维蛋白，可刺激纤溶酶原激活。我们已经分离并鉴定了包含来自λ噬菌体和细菌人工染色体基因组文库的整个人TAFI基因的基因组克隆。完整的TAFI基因包含11个外显子，涵盖约48 kb的基因组DNA。内含子/外显子边界的位置在TAFI基因与大鼠胰腺羧肽酶A1，A2和B与人肥大细胞羧肽酶A基因之间是保守的，表明这些羧肽酶起源于共同的祖先基因。但是，所有这些基因中的内含子长度差异很大。 TAFI启动子缺少共有的TATA序列，并且转录是从多个位点开始的。将包含TAFI 5'侧翼区域部分的报告质粒瞬时转染到哺乳动物细胞中，可以定位启动子，并确定了一个约70 bp的区域，对肝脏特异性转录至关重要。从人肝RNA获得的cDNA克隆的序列分析表明，TAFI转录本在三个不同位点被聚腺苷酸化。我们的发现将有助于通过转录和/或转录后机制评估TAFI表达的调节。此外，了解TAFI基因的基因组结构将有助于鉴定可能与出血或血栓形成倾向相关的突变。

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