NONEXPRESSION OF THE HUMAN SERUM AMYLOID-A 3 (SAA3) GENE

NONEXPRESSION OF THE HUMAN SERUM AMYLOID-A 3 (SAA3) GENE
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DOI:
10.1089/dna.1991.10.651
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发表时间:
1991-11-01
影响因子:
3.1
通讯作者:
BENSON, MD
BENSON, MD
中科院分区:
生物学4区
文献类型:
--
作者:
KLUVEBECKERMAN, B;DRUMM, ML;BENSON, MD

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血清淀粉样蛋白 A (SAA) 是肝脏合成的主要急性期血浆蛋白。 除了人类中描述的两种主要血浆亚型(SAA1 和 SAA2)之外,第三种亚型(SAA3)已在其他几个物种中得到证实,并以主要肝外表达为特征。 本报告描述了含有人类 SAA3 基因的两个克隆 Ch11g5-1-1 和 HDg1-1。 人类 SAA3 基因在组织上与 SAA1 和 SAA2 基因相当,并且在跨越外显子 3 到外显子 4 的区域中与它们具有 87% 的核苷酸同一性。然而,序列 5' 到外显子 3 与 SAA1 和 SAA2 基因中的序列显着不同。 例如,推导的氨基酸1-12(外显子2)序列与人类SAA1和SAA2只有25%的同一性;它与从滑膜成纤维细胞培养物中分离出的兔 SAA3 最相似(75% 同一性)。 虽然兔 SAA3 以自分泌方式诱导胶原酶产生,但人 SAA3 基因不表达。 这通过以下方式显示:(i) 对应于密码子 31 的序列中的单碱基插入,(ii) SAA3 外显子序列紧邻上游的 918 bp 片段无法指导氯霉素乙酰转移酶报道基因的转录,以及 (iii) mRNA 中不存在可检测到的人 SAA3。
Serum amyloid A (SAA) is a major acute-phase plasma protein synthesized by the liver. In addition to the two major plasma isoforms described in humans (SAA1 and SAA2), a third form (SAA3) has been demonstrated in several other species and is distinguished by predominant extrahepatic expression. Two clones, Ch11g5-1-1 and HDg1-1, containing the human SAA3 gene are described in this report. The human SAA3 gene is comparable in organization to the SAA1 and SAA2 genes and shares with them 87% nucleotide identity in the region spanning exon 3 through exon 4. Sequences 5' to exon 3, however, are strikingly different from those in the SAA1 and SAA2 genes. For instance, the sequence deduced for amino acids 1-12 (exon 2) has only 25% identity with human SAA1 and SAA2; it most closely resembles that of rabbit SAA3 isolated from synovial fibroblast cultures (75% identity). Although rabbit SAA3 induces collagenase production in an autocrine fashion the human SAA3 gene is not expressed. This is shown by: (i) a single base insertion in the sequence corresponding to codon 31, (ii) the inability of a 918-bp fragment immediately upstream from SAA3 exon sequences to direct transcription of a chloramphenicol acetyltransferase reporter gene, and (iii) the absence of detectable human SAA3 in mRNA.