NUCLEOTIDE-SEQUENCE OF THE CDNA CODING FOR HUMAN-COMPLEMENT CLR

NUCLEOTIDE-SEQUENCE OF THE CDNA CODING FOR HUMAN-COMPLEMENT CLR
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DOI:
10.1021/bi00365a020
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发表时间:
1986-08-26
期刊:
影响因子:
2.9
通讯作者:
DAVIE, EW
DAVIE, EW
中科院分区:
生物学3区
文献类型:
--
作者:
LEYTUS, SP;KURACHI, K;DAVIE, EW

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CLR是一种丝氨酸蛋白酶的酶原,它参与了补体系统经典途径第一组分的激活。从人肝细胞和Hep G2细胞的Poly(A)RNA文库中分离到编码人ClR的cDNAs。DNA序列分析表明,重叠的插入片段跨越了ClR mRNA的2493个核苷酸,不包括Poly(A)尾。编码ClR的cDNA5‘端非编码区、2115个核苷酸编码705个氨基酸的多肽前体和3’端非编码区。在3‘’非编码序列的长度上观察到了一些变化,尽管大多数插入片段都含有一个多聚腺苷基化信号和一个多聚(A)尾巴。ClR的A链或非催化链起源于前体分子的氨基末端,含有一个潜在的生长因子结构域和两对不同的内部重复序列。这些内部重复序列中的一对与CLS的氨基末端序列密切相关,而另一对重复序列与存在于β2-糖蛋白I、补体因子B、因子XIII的b亚基以及存在于结合珠蛋白的α1链中的单个区域的串联重复序列同源。ClR的B链包含酶的催化部分,与丝氨酸蛋白酶的胰酶家族同源。
Clr is a zymogen of a serine protease that is involved in the activation of the firse component of the classical pathway of the complement system. cDNAs coding for human Clr have been isolated from libraries prepared from poly(A) RNA from human liver and Hep G2 cells. From DNA sequence analysis, the overlapping cDNA inserts were shown to span 2493 nucleotides of the Clr mRNA, not including the poly(A) tail. The cDNA sequence coding for Clr contained a 5'' noncoding region, 2115 nucleotides coding for a polypeptide precursor of 705 amino acids, and a 3'' noncoding region. Some variability in the length of the 3'' noncoding sequence was observed with the cDNA inserts, although most contained a polyadenylation signal followed by a poly(A) tail. The A or noncatalytic chain of Clr, which originates from the amino-terminal end of the precursor molecule, contains a potential growth factor domain and two different pairs of internal repeats. One pair of these internal repeats is closely related to the amino-terminal sequence of Cls, while the other pair of repeats is homologous to the tandem repeats present in .beta.2-glycoprotein I, complement factor B, the b subunit of factor XIII, and a single region present in the .alpha.1 chain of haptoglobin. The B chain of Clr contains the catalytic portion of the enzyme and is homologous to the trypsin family of serine proteases.