Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor

Cloning and characterization of the gene encoding human osteoprotegerin/osteoclastogenesis-inhibitory factor
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DOI:
10.1046/j.1432-1327.1998.2540685.x
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发表时间:
1998-06-15
期刊:
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子:
--
通讯作者:
Higashio, K
Higashio, K
中科院分区:
其他
文献类型:
--
作者:
Morinaga, T;Nakagawa, N;Higashio, K

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人骨保护素(OPG)-破骨细胞生成抑制因子(OCIF)基因已被克隆和鉴定。OPG-OCIF基因是由5个外显子组成的单拷贝基因,跨越人类基因组的29 kb。所有外显子/内含子边界符合GT/AG规则。终止密码子存在于外显子5中,并且典型的poly(A)-添加信号位于终止密码子下游173个核苷酸处。一个主要的转录起始位点存在于起始ATG密码子上游67个核苷酸处。上游有两个较小的站点。在IMR-90细胞中检测到的4.2-kb和6.5-kb转录物被发现分别含有内含子2的3 '-一半和整个内含子2。在OPG-OCIF基因中,单个内含子将编码四个富含Cys的基序的延伸分开,这意味着与肿瘤坏死因子受体(TNFR)家族的其他成员的多样性。OPG-OCIF中串联存在的两个死亡结构域同源区(DDH)分别由外显子4和5编码。氨基酸序列的保守性表明外显子4是由外显子5的一部分复制产生的。
The human osteoprotegerin (OPG)-osteoclastogenesis-inhibitory factor (OCIF) gene has been cloned and characterized. The OPG-OCIF gene is a single-copy gene consisting of five exons, and spans 29 kb of the human genome. All the exon/intron boundaries comply with the GT/AG rule. The translation-termination codon is present in exon 5 and a typical poly(A)-addition signal resides 173-nucleotides downstream of the translation-termination codon. A major transcription-initiation site is present 67-nucleotides upstream of the initiation ATG codon. Two minor sites are present further upstream. The 4.2-kb and 6.5-kb transcripts detected in IMR-90 cells were found to contain the 3'-half of intron 2 and the entire intron 2, respectively. In the OPG-OCIF gene, a single intron divides the stretch that encode four Cys-rich motifs, implying diversity from the other members of the tumor necrosis factor receptor (TNFR) family. Two death domain homologous regions (DDHs) present in tandem in OPG-OCIF are encoded separately by exons 4 and 5. The conservation of amino-acid sequences suggests that exon 4 is produced by a duplication of a portion of exon 5.