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亲环素A是免疫抑制剂环孢素A的主要细胞内受体,定位于7号染色体p11.2 - p13区域;有四个假基因分别定位于3号、10号、14号和18号染色体。

Cyclophilin A, the major intracellular receptor for the immunosuppressant cyclosporin A, maps to chromosome 7p11.2-p13: four pseudogenes map to chromosomes 3, 10, 14, and 18.

作者信息

Willenbrink W, Halaschek J, Schuffenhauer S, Kunz J, Steinkasserer A

机构信息

Sandoz Research Institute, Vienna, Austria.

出版信息

Genomics. 1995 Jul 1;28(1):101-4. doi: 10.1006/geno.1995.1112.

DOI:10.1006/geno.1995.1112
PMID:7590732
Abstract

Cyclophilin A (CyP-A), the major intracellular receptor for the immunosuppressant cyclosporin A (CsA), is a member of the immunophilin class of proteins, which all possess peptidyl-prolyl cis-trans isomerase activity and, therefore, are believed to be involved in protein folding and/or intracellular protein transport. The CyP-A protein is encoded by a single gene; in addition, 15 pseudogenes have been identified. Recently, specific binding of CyP-A to the human immunodeficiency virus type 1 (HIV-1) gag protein has been reported. Interestingly, this interaction can be inhibited by the immunosuppressant CsA and also by nonimmunosuppressive, CyP-A-binding CsA derivatives, which were also shown to exhibit potent anti-HIV-1 activity. Results thus indicate that CyP-A may have an essential function in HIV-1 replication. Using a panel of somatic rodent-human cell hybrids and PCR technology, we localized the coding cyclophilin A gene (PPIA) on chromosome 7 and four pseudogenes (PPIP2, PPIP3, PPIP4, and PPIP6) on chromosomes 14, 10, 18, and 3, respectively. Using chromosome 7 and chromosome 10 deletion hybrid panels, we were able to localize further the coding gene to the region 7p11.2-p13, as confirmed by fluorescence in situ hybridization analysis, and one pseudogene (PPIP3) to the region 10q11.2-q23. This is the first report on the regional mapping of members of the CyP-A gene family.

摘要

亲环素A(CyP-A)是免疫抑制剂环孢素A(CsA)的主要细胞内受体,属于亲免素类蛋白质成员,这类蛋白质都具有肽基脯氨酰顺反异构酶活性,因此被认为参与蛋白质折叠和/或细胞内蛋白质转运。CyP-A蛋白由单一基因编码;此外,已鉴定出15个假基因。最近,有报道称CyP-A与人免疫缺陷病毒1型(HIV-1)的gag蛋白存在特异性结合。有趣的是,这种相互作用可被免疫抑制剂CsA以及非免疫抑制性的、能与CyP-A结合的CsA衍生物抑制,这些衍生物也显示出强大的抗HIV-1活性。因此结果表明,CyP-A可能在HIV-1复制中具有重要功能。利用一组体细胞啮齿动物-人类细胞杂种和PCR技术,我们将亲环素A编码基因(PPIA)定位到7号染色体上,将四个假基因(PPIP2、PPIP3、PPIP4和PPIP6)分别定位到14号、10号、18号和3号染色体上。利用7号染色体和10号染色体缺失杂种细胞系,我们能够将编码基因进一步定位到7p11.2-p13区域,荧光原位杂交分析证实了这一点,并将一个假基因(PPIP3)定位到10q11.2-q23区域。这是关于CyP-A基因家族成员区域定位的首次报道。

相似文献

1
Cyclophilin A, the major intracellular receptor for the immunosuppressant cyclosporin A, maps to chromosome 7p11.2-p13: four pseudogenes map to chromosomes 3, 10, 14, and 18.亲环素A是免疫抑制剂环孢素A的主要细胞内受体,定位于7号染色体p11.2 - p13区域;有四个假基因分别定位于3号、10号、14号和18号染色体。
Genomics. 1995 Jul 1;28(1):101-4. doi: 10.1006/geno.1995.1112.
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A receptor for the immunosuppressant FK506 is a cis-trans peptidyl-prolyl isomerase.免疫抑制剂FK506的一种受体是一种顺反肽基脯氨酰异构酶。
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Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy.通过X射线晶体学和核磁共振光谱法确定的人亲环蛋白的结构及其与环孢菌素A的结合位点。
Nature. 1991 Sep 19;353(6341):276-9. doi: 10.1038/353276a0.
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Specific incorporation of cyclophilin A into HIV-1 virions.亲环素A特异性掺入HIV-1病毒颗粒。
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Peptidyl-prolyl cis-trans isomerase of Bacillus subtilis: identification of residues involved in cyclosporin A affinity and catalytic efficiency.枯草芽孢杆菌的肽基脯氨酰顺反异构酶:鉴定与环孢菌素A亲和力和催化效率相关的残基
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Yeast cyclophilin-related gene encodes a nonessential second peptidyl-prolyl cis-trans isomerase associated with the secretory pathway.酵母亲环素相关基因编码一种与分泌途径相关的非必需的第二种肽基脯氨酰顺反异构酶。
Transplant Proc. 1991 Dec;23(6):2856-61.
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Isolation, characterization and targeted disruption of mouse ppia: cyclophilin A is not essential for mammalian cell viability.小鼠ppia的分离、特性鉴定及靶向破坏:亲环蛋白A对哺乳动物细胞生存力并非必不可少。
Genomics. 2000 Sep 1;68(2):167-78. doi: 10.1006/geno.2000.6295.
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A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin.免疫抑制剂FK506的一种胞质结合蛋白具有肽基脯氨酰异构酶活性,但与亲环蛋白不同。
Nature. 1989 Oct 26;341(6244):755-7. doi: 10.1038/341755a0.
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Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding.从粗糙脉孢菌中分离出一种催化蛋白质折叠的FK506结合蛋白并测定其序列。
Nature. 1990 Aug 16;346(6285):674-7. doi: 10.1038/346674a0.

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Microglia are both a source and target of extracellular cyclophilin A.小胶质细胞既是细胞外亲环素A的来源,也是其作用靶点。
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The roles of CD147 and/or cyclophilin A in kidney diseases.CD147和/或亲环素A在肾脏疾病中的作用。
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Cyclophilin A is required for efficient human cytomegalovirus DNA replication and reactivation.亲环蛋白 A 对于有效的人类巨细胞病毒 DNA 复制和再激活是必需的。
J Gen Virol. 2012 Apr;93(Pt 4):722-732. doi: 10.1099/vir.0.037309-0. Epub 2012 Jan 13.
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Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome.数百万年的进化得以保留:人类基因组中加工假基因的综合目录。
Genome Res. 2003 Dec;13(12):2541-58. doi: 10.1101/gr.1429003.