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编码抗凝血蛋白C的小鼠基因的核苷酸结构与特性

Nucleotide structure and characterization of the murine gene encoding anticoagulant protein C.

作者信息

Jalbert L R, Rosen E D, Lissens A, Carmeliet P, Collen D, Castellino F J

机构信息

Department of Chemistry and Biochemistry and the Center for Transgene Research, University of Notre Dame, Indiana 46556, USA.

出版信息

Thromb Haemost. 1998 Feb;79(2):310-6.

PMID:9493582
Abstract

The 15,160 bp murine gene encoding anticoagulation protein C (PC) was cloned and sequenced, including 414 bp upstream of exon 1 and 80 bp downstream of the translation stop codon. Nine exons and eight introns were identified. The first exon was untranslated and contained the major transcriptional start site, the surrounding nucleotide sequence of which matched reasonably well with the consensus eukaryotic Cap element sequence. The translational initiator methionine residue was located in exon 2. The other introns were positioned as splices between the major domain units of the protein. The 5' untranslated region contained two possible CCAAT sequences and GC boxes, but no TATA box was obvious within the optimal range of distances from the transcription start site. The 3'-flanking nucleotides included a probable polyadenylation site (ATTAAA), beginning 80 nucleotides downstream of the translation stop codon, and a downstream consensus sequence (AGTGTTTC) required for the efficient formation of a 3' terminus of mRNA. Several high probability transcription factor recognition sequences, including proteins that are enriched in, or specific to, the liver, such as C/EBP alpha, C/EBP beta, HNF1, and HNF3 beta, have been located in the 5' region of the gene. These results indicate that all elements are present for liver-based transcription of the gene for murine PC.

摘要

对编码抗凝蛋白C(PC)的15160 bp小鼠基因进行了克隆和测序,包括外显子1上游414 bp和翻译终止密码子下游80 bp。鉴定出9个外显子和8个内含子。第一个外显子是非翻译的,包含主要转录起始位点,其周围核苷酸序列与真核生物帽元件共有序列相当匹配。翻译起始甲硫氨酸残基位于外显子2中。其他内含子位于蛋白质主要结构域单元之间的剪接处。5'非翻译区包含两个可能的CCAAT序列和GC盒,但在距转录起始位点的最佳距离范围内未发现明显的TATA盒。3'侧翼核苷酸包括一个可能的聚腺苷酸化位点(ATTAAA),位于翻译终止密码子下游80个核苷酸处,以及mRNA 3'末端有效形成所需的下游共有序列(AGTGTTTC)。在该基因的5'区域发现了几个高概率转录因子识别序列,包括在肝脏中富集或特异的蛋白质,如C/EBPα、C/EBPβ、HNF1和HNF3β。这些结果表明,小鼠PC基因基于肝脏转录所需的所有元件均已存在。

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引用本文的文献

1
Combined factor VII/protein C deficiency results in intrauterine coagulopathy in mice.凝血因子VII/蛋白C联合缺乏导致小鼠宫内凝血障碍。
J Clin Invest. 2000 Apr;105(7):897-903. doi: 10.1172/JCI9095.
2
Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice.抗凝血蛋白C基因的失活会导致小鼠出现致死性围产期消耗性凝血病。
J Clin Invest. 1998 Oct 15;102(8):1481-8. doi: 10.1172/JCI3011.