Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex.
Dancing with complement C4 and the RP-C4-CYP21-TNX (RCCX) modules of the major histocompatibility complex.
复制标题
与主要组织相容性复合物的补体 C4 和 RP-C4-CYP21-TNX (RCCX) 模块共舞。
DOI：
10.1016/s0079-6603(03)75007-7
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Fust,George
中科院分区：
文献类型：
--
作者：
Yu,CYung;Chung,ErwinK;Yang,Yan;Blanchong,CarolA;Jacobsen,Natalie;Saxena,Kapil;Yang,Zhenyu;Miller,Webb;Varga,Lilian;Fust,George
在不同的人类个体中，二倍体基因组中补体成分C4基因的数量从2到8不等。高加索人群中四分之三的C4基因在第九内含子中具有内源性逆转录病毒HERV-K（C4）。其余的则不然。C4血清蛋白具有高度多态性，其浓度范围为100至约1000 μ g/ml。存在两种不同类别的C4蛋白，C4 A和C4 B，其已经多样化以分别实现（a）调理/免疫清除目的和（B）在通过溶解和中和杀死微生物中的众所周知的补体功能。许多感染性和自身免疫性疾病与C4 A和/或C4 B的完全或部分缺乏有关。然而，随着人类C4遗传学概念的修正和精确技术的应用，高C4基因剂量的不利影响才刚刚出现，以区分部分缺陷和由不相等的C4 A和C4 B基因剂量和基因大小引起的差异表达。本文综述了补体C4 A和C4 B的复杂遗传学。重点是C4基因型和表型的定性和定量分析。描述了人类和小鼠C4蛋白的许多同种异型变体和加工产物。研究了C4基因与丝氨酸/苏氨酸核激酶基因RP、类固醇21-羟化酶CYP 21和细胞外基质蛋白TNX（RCCX模块）的模块化变化对C4蛋白多态性的均质化的影响，以及对敲除CYP 21和/或TNX功能的不平等遗传交叉的影响。此外，内源性逆转录病毒HERV-K（C4）对C4基因表达的影响和HERV-K（C4）家族成员在人类基因组中的分布进行了讨论。
The number of the complement component C4 genes varies from 2 to 8 in a diploid genome among different human individuals. Three quarters of the C4 genes in Caucasian populations have the endogenous retrovirus, HERV-K (C4), in the ninth intron. The remainder does not. The C4 serum proteins are highly polymorphic and their concentrations vary from 100 to approximately 1000 microg/ml. There are two distinct classes of C4 protein, C4A and C4B, which have diversified to fulfill (a) the opsonization/immunoclearance purposes and (b) the well-known complement function in the killing of microbes by lysis and neutralization, respectively. Many infectious and autoimmune diseases are associated with complete or partial deficiency of C4A and/or C4B. The adverse effects of high C4 gene dosages, however, are just emerging, as the concepts of human C4 genetics are revised and accurate techniques are applied to distinguish partial deficiencies from differential expression caused by unequal C4A and C4B gene dosages and gene sizes. This review attempts to dissect the sophisticated genetics of complement C4A and C4B. The emphases are on the qualitative and quantitative diversities of C4 genotypes and phenotypes. The many allotypic variants and the processed products of human and mouse C4 proteins are described. The modular variation of C4 genes together with the serine/threonine nuclear kinase gene RP, the steroid 21-hydroxylase CYP21, and extracellular matrix protein TNX (RCCX modules) are investigated for the effects on homogenization of C4 protein polymorphisms, and on the unequal genetic crossovers that knocked out the functions of CYP21 and/or TNX. Furthermore, the influence of the endogenous retrovirus HERV-K (C4) on C4 gene expression and the dispersal of HERV-K (C4) family members in the human genome are discussed.