COMPLETE SEQUENCE OF THE CDNA FOR HUMAN ALPHA-1-ANTITRYPSIN AND THE GENE FOR THE S-VARIANT
COMPLETE SEQUENCE OF THE CDNA FOR HUMAN ALPHA-1-ANTITRYPSIN AND THE GENE FOR THE S-VARIANT
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DOI：
10.1021/bi00316a003
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发表时间：
1984-01-01
期刊：
影响因子：
2.9
通讯作者：
KURACHI, K
中科院分区：
文献类型：
--
作者：
LONG, GL;CHANDRA, T;KURACHI, K
分离编码整个α 1-抗胰蛋白酶蛋白的1434碱基对人肝cDNA [互补DNA]并测序。将编码区翻译成氨基酸揭示了含有24个氨基酸的信号肽和存在于成熟多肽链中的394个氨基酸的前体分子。还对α 1-抗胰蛋白酶S变体的人基因进行亚克隆和测序。该基因由10226个核苷酸碱基组成，并且对于所有4个核苷酸来说是大约等摩尔的。该基因含有4个插入序列（内含子）和5 "和3"非编码区，其长度分别为54和79个核苷酸。在5 "非编码区存在一个5.3-腺苷酸酶内含子，包含一个143个氨基酸的开放阅读框、一个Alu家族序列和一个假转录起始区。在内含子和对应于相应mRNA的编码区的那些区域（外显子）之间未观察到碱基组成的显著差异。还确定了基因5 "端侧翼的1951个核苷酸的序列，并且在所提出的转录起始位点上游21个核苷酸的上游含有" TATA "盒序列（TTAAATA）。基因序列与cDNA序列的比较揭示了一个单碱基取代（A → C）。T），这导致Glu → D。S变体蛋白中位置264的瓦尔取代。α 1-抗胰蛋白酶基因的内含子的位置和大小、总的碱基组成和密码子偏好与鸡卵清蛋白基因的不同，即使这两种蛋白质属于共同的蛋白质家族，如通过氨基酸序列同源性所判断的。
A 1434 base pair human liver cDNA [complementary DNA] coding for the entire .alpha.1-antitrypsin protein was isolated and sequenced. Translation of the coding region into amino acids reveals a precursor molecule which contains a 24 amino acid signal peptide and 394 amino acids present in the mature polypeptide chain. The human gene for the S variant of .alpha.1-antitrypsin was also subcloned and sequenced. The gene is composed of 10226 nucleotide bases and is approximately equimolar for all 4 nucleotides. The gene contains 4 intervening sequences (introns) and 5'' and 3'' noncoding regions which are 54 and 79 nucleotides in length, respectively. A 5.3-kilobase intron exists in the 5'' noncoding region and contains a 143 amino acid open reading frame, an Alu family sequence, and a pseudo transcription initiation region. No significant differences in base composition are seen between the introns and those regions corresponding to coding regions of the corresponding mRNA (exons). A sequence of 1951 nucleotides flanking the 5'' end of the gene was also determined and contains a "TATA" box sequence (TTAAATA) 21 nucleotides upstream upstream from the proposed transcription start site. Comparison of the gene sequence with the cDNA sequence reveals a single base substitution (A .fwdarw. T), which results in a Glu .fwdarw. Val substitution of position 264 in the S variant protein. The position and size of introns, the overall base composition, and the codon preference for the .alpha.1-antitrypsin gene differ from those for the chicken ovalbumin gene even though the 2 proteins belong to a common protein family, as judged by amino acid sequence homology.