Race J E, Makhlouf F N, Logue P J, Wilson F H, Dunham P B, Holtzman E J
Renal Division, Department of Medicine, State University of New York Health Science Center, Syracuse 13210, New York.
Am J Physiol. 1999 Dec;277(6):C1210-9. doi: 10.1152/ajpcell.1999.277.6.C1210.
We isolated and characterized a novel K-Cl cotransporter, KCC3, from human placenta. The deduced protein contains 1,150 amino acids. KCC3 shares 75-76% identity at the amino acid level with human, pig, rat, and rabbit KCC1 and 67% identity with rat KCC2. KCC3 is 40 and 33% identical to two Caenorhabditis elegans K-Cl cotransporters and approximately 20% identical to other members of the cation-chloride cotransporter family (CCC), two Na-K-Cl cotransporters (NKCC1, NKCC2), and the Na-Cl cotransporter (NCC). Hydropathy analysis indicates a typical KCC topology with 12 transmembrane domains, a large extracellular loop between transmembrane domains 5 and 6 (unique to KCCs), and large NH(2) and COOH termini. KCC3 is predominantly expressed in kidney, heart, and brain, and is also expressed in skeletal muscle, placenta, lung, liver, and pancreas. KCC3 was localized to chromosome 15. KCC3 transiently expressed in human embryonic kidney (HEK)-293 cells fulfilled three criteria for increased expression of K-Cl cotransport: stimulation of cotransport by swelling, treatment with N-ethylmaleimide, or treatment with staurosporine.
我们从人胎盘中分离并鉴定出一种新型钾氯共转运体KCC3。推导的蛋白质含有1150个氨基酸。KCC3在氨基酸水平上与人、猪、大鼠和兔的KCC1具有75 - 76%的同一性，与大鼠的KCC2具有67%的同一性。KCC3与两种秀丽隐杆线虫钾氯共转运体的同一性为40%和33%，与阳离子氯共转运体家族（CCC）的其他成员、两种钠钾氯共转运体（NKCC1、NKCC2）以及钠氯共转运体（NCC）的同一性约为20%。亲水性分析表明KCC3具有典型的拓扑结构，有12个跨膜结构域，在跨膜结构域5和6之间有一个大的细胞外环（KCCs所特有的），以及较大的氨基和羧基末端。KCC3主要在肾脏、心脏和大脑中表达，也在骨骼肌、胎盘、肺、肝脏和胰腺中表达。KCC3定位于15号染色体。在人胚肾（HEK）- 293细胞中瞬时表达的KCC3满足钾氯共转运增加表达的三个标准：通过肿胀、用N - 乙基马来酰亚胺处理或用星形孢菌素处理来刺激共转运。
