George A L, Knittle T J, Tamkun M M
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4893-7. doi: 10.1073/pnas.89.11.4893.
Previously cloned voltage-dependent sodium channels exhibit a high degree of homology to one another and appear to comprise a single multigene family. We have now isolated and characterized cDNAs from both human adult heart and fetal skeletal muscle that encode a sodium channel alpha subunit that exhibits only moderate primary structure identity with other sodium channels and is prominently expressed in both heart and uterus. The approximately 7.2-kilobase cDNA sequence, designated hNav2.1, predicts a 1682-amino acid protein that bears 52%, 49%, and 46% overall identity with sodium channels cloned from rat brain, skeletal muscle, and heart, respectively. Positively charged S4 segments are present in hNav2.1, but there are fewer basic residues in repeat domains 1, 3, and 4 than in other cloned sodium channels. The cloning of hNav2.1 provides evidence for greater evolutionary divergence among voltage-dependent sodium channels and suggests that other sodium channel gene subfamilies may exist. The unique amino acid sequences in regions known to be involved in voltage-dependent activation and inactivation suggest that hNav2.1 will have novel gating properties.
先前克隆的电压依赖性钠通道彼此间表现出高度的同源性，似乎构成了一个单一的多基因家族。我们现已从成人心脏和胎儿骨骼肌中分离并鉴定出编码钠通道α亚基的cDNA，该亚基与其他钠通道仅表现出中等程度的一级结构一致性，且在心脏和子宫中均有显著表达。这个约7.2千碱基的cDNA序列，命名为hNav2.1，预测编码一个1682个氨基酸的蛋白质，该蛋白质与从大鼠脑、骨骼肌和心脏克隆的钠通道分别具有52%、49%和46%的总体一致性。hNav2.1中存在带正电荷的S4片段，但重复结构域1、3和4中的碱性残基比其他克隆的钠通道少。hNav2.1的克隆为电压依赖性钠通道之间更大的进化差异提供了证据，并表明可能存在其他钠通道基因亚家族。已知参与电压依赖性激活和失活的区域中的独特氨基酸序列表明，hNav2.1将具有新的门控特性。
