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Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins.

机译:DDAH1的染色体定位,基因结构和表达模式:与DDAH2的比较及其对进化起源的影响。

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Endogenously produced asymmetrically methylated arginine residues are competitive inhibitors of all three isoforms of nitric oxide synthase (NOS). The enzyme dimethylarginine dimethylaminohydrolase (DDAH) specifically hydrolyzes these asymmetrically methylated arginine residues to citrulline and methylamines. Previously we have proposed that regulation of asymmetric methylarginine concentration by DDAH may provide a novel mechanism for the regulation of NOS activity in vivo. Recently we reported the cloning of human DDAH and identified a novel human DDAH isoform (DDAH I and DDAH II, respectively). Here we report that the DDAH1 gene maps to chromosome 1p22 and confirm that DDAH2 maps to the MHC III region of chromosome 6p21.3. Extensive analysis of the distribution of DDAH1 and DDAH2 mRNA in 50 human tissues indicates differential expression of DDAH isoforms in brain regions, in immune cells, and during development. DDAH2 expression predominates in highly vascularized tissues that express the endothelial NOS isoform and in immune tissues that can express iNOS. Whereas DDAH2 is expressed at relatively high levels in all fetal tissues examined, DDAH1 expression varies little between fetal and adult tissues. The chromosomal localization of the DDAHs is consistent with gene duplication, and consistent with this, comparison of the gene structures indicates that the intron/exon organization is highly conserved. Phylogenetic analysis of DDAH sequences from diverse species suggests that DDAH gene duplication occurred prior to the emergence of bony fish some 400 million years ago. Overall the data suggest that DDAH2 may be the more ancient of the two genes. Copyright 2000 Academic Press.
机译:内源性产生的不对称甲基化精氨酸残基是一氧化氮合酶(NOS)三种同工型的竞争性抑制剂。酶二甲基精氨酸二甲基氨基水解酶(DDAH)专门将这些不对称甲基化的精氨酸残基水解为瓜氨酸和甲胺。以前我们已经提出,DDAH对不对称甲基精氨酸浓度的调节可能为体内NOS活性的调节提供新的机制。最近,我们报道了人DDAH的克隆,并鉴定了一种新型的人DDAH亚型(分别为DDAH I和DDAH II)。在这里我们报告DDAH1基因映射到染色体1p22,并确认DDAH2映射到染色体6p21.3的MHC III区。 DDAH1和DDAH2 mRNA在50个人体组织中的分布的广泛分析表明DDAH亚型在大脑区域,免疫细胞和发育过程中的差异表达。 DDAH2表达在表达内皮型NOS同工型的高度血管化组织和可以表达iNOS的免疫组织中占主导地位。尽管在所有检查的胎儿组织中DDAH2的表达水平都较高,但在胎儿和成人组织中DDAH1的表达变化很小。 DDAHs的染色体定位与基因重复一致,并且与此一致,基因结构的比较表明内含子/外显子组织是高度保守的。对不同物种的DDAH序列进行系统发育分析表明,DDAH基因复制发生在大约4亿年前的骨鱼出现之前。总体而言,数据表明DDAH2可能是两个基因中更古老的一个。版权所有2000学术出版社。

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