Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse,fish,fly,and worm  

作　　者：Chun-Xia Wang Andreas Teufel Uta Cheruti Joachim Groetzinger Peter R Galle Ansgar W Lohse Johannes Herkel 

机构地区：[1]I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany [2]Shandong University Shandong Provincial Hospital, Jinan, Shandong Province, China [3]I. Department ofMedicine, Johannes Gutenberg University, Mainz, Germany [4]Institute of Biochemistry, Christian-Albretchts-University, Kiel, Germany

出　　处：《World Journal of Gastroenterology》2006年第6期902-907,共6页世界胃肠病学杂志（英文版）

基　　金：Supported by the Deutsche Forschungsgemeinschaft(SFB 548)

摘　　要：AIM： To approach the elusive function of the SLA/LP molecule, we have characterized genomic organization and conservation of the major antigenic and functional properties of the SLA/LP molecule in various species. METHODS： By means of computational biology, we have characterized the complete SLA/LP gene, mRNA and deduced protein sequences in man, mouse, zebrafish, fly, and worm. RESULTS： The human SLA/LP gene sequence of approximately 39 kb, which maps to chromosome 4p15.2, is organized in 11 exons, of which 10 or 11 are translated, depending on the splice variant. Homologous molecules were identified in several biological model organisms. The various homologous protein sequences showed a high degree of similarity or homology, notably at those residues that are of functional importance. The only domain of the human protein sequence that lacks significant homology with homologous sequences is the major antigenic epitope recognized by autoantibodies from autoimmune hepatitis （AIH） patients. CONCLUSION： The SLA/LP molecule and its functionally relevant residues have been highly conserved throughout the evoluti n, suggesting an indispensable function of the molecule. The finding that the only non-conserved domain is the dominant antigenic epitope of the human SLA/LP sequence, suggests that SLA/LP autoimmunity is autoantigen-driven rather than being driven by molecular mimicry.瞄准：来临逃犯 SLA/LP 分子的功能，我们在各种各样的种类描绘了 genomic 组织和遗传因子的主要的反和 SLA/LP 分子的功能的性质的保存。方法：借助于计算生物学，我们在人，老鼠，斑马鱼，苍蝇，和蠕虫描绘了完全的 SLA/LP 基因， mRNA 和推出的蛋白质序列。结果：约 39 kb 的人的 SLA/LP 基因顺序，印射到染色体 4p15.2，在 11 前 ons， 10 或 11 被翻译被组织，取决于 splice 变体。相应分子在几个生物模型有机体被识别。各种各样的相应蛋白质序列显示出类似或相同的高度，尤其是在功能的重要性的那些残余。与相应序列缺乏重要相同的人的蛋白质顺序的唯一的领域是遗传因子的 epitope 从自体免疫的肝炎(AIH ) 由自身抗体认出了的主要的反病人。结论：SLA/LP 分子和它的机能上地相关的残余高度在整个进化被保存了，建议分子的不可缺少的功能。发现那个唯一的非保存的领域是人的 SLA/LP 的遗传因子的 epitope 定序的主导的反，建议 SLA/LP 汽车免疫是驾驶 autoantigen 的而非被分子的模仿驾驶。

关 键 词：Autoimmune hepatitis AUTOANTIGEN GENOMICS Bioinformatics 

分 类 号：Q78[生物学—分子生物学]