Pountney D J, Gulkarov I, Vega-Saenz de Miera E, Holmes D, Saganich M, Rudy B, Artman M, Coetzee W A
Department of Pediatric Cardiology, New York University School of Medicine, NY 10016, USA.
FEBS Lett. 1999 May 7;450(3):191-6. doi: 10.1016/s0014-5793(99)00495-0.
We have identified and cloned a new member of the mammalian tandem pore domain K+ channel subunit family, TWIK-originated similarity sequence, from a human testis cDNA library. The 939 bp open reading frame encodes a 313 amino acid polypeptide with a calculated Mr of 33.7 kDa. Despite the same predicted topology, there is a relatively low sequence homology between TWIK-originated similarity sequence and other members of the mammalian tandem pore domain K+ channel subunit family group. TWIK-originated similarity sequence shares a low (< 30%) identity with the other mammalian tandem pore domain K+ channel subunit family group members and the highest identity (34%) with TWIK-1 at the amino acid level. Similar low levels of sequence homology exist between all members of the mammalian tandem pore domain K+ channel subunit family. Potential glycosylation and consensus PKC sites are present. Northern analysis revealed species and tissue-specific expression patterns. Expression of TWIK-originated similarity sequence is restricted to human pancreas, placenta and heart, while in the mouse, TWIK-originated similarity sequence is expressed in the liver. No functional currents were observed in Xenopus laevis oocytes or HEK293T cells, suggesting that TWIK-originated similarity sequence may be targeted to locations other than the plasma membrane or that TWIK-originated similarity sequence may represent a novel regulatory mammalian tandem pore domain K+ channel subunit family subunit.
我们从人睾丸cDNA文库中鉴定并克隆出哺乳动物双孔结构域K⁺通道亚基家族的一个新成员，即TWIK起源相似序列。939 bp的开放阅读框编码一个313个氨基酸的多肽，计算所得的分子量为33.7 kDa。尽管预测的拓扑结构相同，但TWIK起源相似序列与哺乳动物双孔结构域K⁺通道亚基家族组的其他成员之间的序列同源性相对较低。TWIK起源相似序列与其他哺乳动物双孔结构域K⁺通道亚基家族组成员的氨基酸序列一致性较低（<30%），与TWIK-1的一致性最高（34%）。哺乳动物双孔结构域K⁺通道亚基家族的所有成员之间都存在类似的低水平序列同源性。存在潜在的糖基化位点和共有蛋白激酶C位点。Northern印迹分析揭示了物种和组织特异性表达模式。TWIK起源相似序列的表达仅限于人胰腺、胎盘和心脏，而在小鼠中，TWIK起源相似序列在肝脏中表达。在非洲爪蟾卵母细胞或HEK293T细胞中未观察到功能性电流，这表明TWIK起源相似序列可能定位于质膜以外的位置，或者TWIK起源相似序列可能代表一种新型的调节性哺乳动物双孔结构域K⁺通道亚基家族亚基。
