Rodriguez de Cordoba S, Sanchez-Corral P, Rey-Campos J
Unidad de Immunología, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
J Exp Med. 1991 May 1;173(5):1073-82. doi: 10.1084/jem.173.5.1073.
The human gene coding for the 70-kD polypeptide of the complement regulatory component C4b-binding protein (C4BP alpha) spans over 40 kb of DNA and is composed of twelve exons. Upon transcription in liver, or in Hep-G2 cells, this gene produces a single transcript of 2,262 nucleotides, excepting the poly A tail, that presents an unusually long 5' untranslated region (5' UTR) of 223 nucleotides. The C4BP alpha gene is organized as follows: the first exon codes for the first 198 nucleotides of the 5' UTR. It is separated by a large intron from the second exon including the remaining of the 5' UTR and the coding region for the signal peptide. Each of the eight 60-amino acid repeats (short consensus repeats [SCRs]) that compose the C4BP alpha polypeptide chain is encoded by a single exon, except for the second SCR, which is split in two exons. At the 3' end of the C4BP alpha gene, the twelfth exon codes for the COOH-terminal 57 amino acids of the mature protein, which have no similarities to the SCRs, and the 245 nucleotides of the 3' UTR. Examination of the nucleotide sequence of the first exon revealed an interesting characteristic, strongly suggesting that this exon may specify a functional domain of the C4BP alpha transcript. It includes two in-phase ATG codons, in a different frame respect to that coding the C4BP alpha polypeptide, followed by an in-frame termination codon, also within the first exon. Comparison between mouse and human C4BP alpha transcripts indicates conservation of this structure within the 5' UTR. C4BP is expressed in the liver and is an acute phase protein. A computer search of the genomic sequences upstream the transcription start site demonstrates the presence of potential cis-acting regulatory elements similar to those found in the promoters of other liver-expressed and/or acute phase genes.
编码补体调节成分C4b结合蛋白（C4BPα）70-kD多肽的人类基因跨越超过40 kb的DNA，由12个外显子组成。在肝脏或Hep-G2细胞中转录时，该基因产生一个2262个核苷酸的单一转录本（不包括聚腺苷酸尾），其5'非翻译区（5'UTR）异常长，为223个核苷酸。C4BPα基因的组织方式如下：第一个外显子编码5'UTR的前198个核苷酸。它与第二个外显子由一个大内含子隔开，第二个外显子包括5'UTR的其余部分和信号肽的编码区。组成C4BPα多肽链的八个60个氨基酸重复序列（短共有重复序列[SCRs]）中的每一个都由一个单一外显子编码，但第二个SCR除外，它被分成两个外显子。在C4BPα基因的3'端，第十二个外显子编码成熟蛋白的COOH末端57个氨基酸，这些氨基酸与SCRs没有相似性，以及3'UTR的245个核苷酸。对第一个外显子核苷酸序列的检查揭示了一个有趣的特征，强烈表明该外显子可能指定了C4BPα转录本的一个功能域。它包括两个同相的ATG密码子，与编码C4BPα多肽的密码子处于不同的阅读框，随后是一个也在第一个外显子内的框内终止密码子。小鼠和人类C4BPα转录本之间的比较表明5'UTR内这种结构的保守性。C4BP在肝脏中表达，是一种急性期蛋白。对转录起始位点上游基因组序列的计算机搜索表明存在与其他肝脏表达和/或急性期基因启动子中发现的潜在顺式作用调节元件相似的元件。
