Cai Shi-Ying, Wang Wei, Soroka Carol J, Ballatori Nazzareno, Boyer James L
Liver Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G702-10. doi: 10.1152/ajpgi.00458.2001.
Cellular uptake of organic solutes is mediated in large part by a gene family of membrane transporters called OATPs (SLC21A). To study the structural determinants and evolutionary development of the SLC21A family, we have cloned and functionally characterized a highly expressed evolutionarily primitive Oatp from the liver of the small skate, Raja erinacea. A full-length cDNA (2.3 kb) was obtained that encodes a protein of 689 amino acids. The characteristics of this novel skate Oatp, including tissue expression, subcellular localization, substrate selectivity, Na(+) dependence, and inhibitor selectivity were generally similar to liver-specific human OATP-C and rat Oatp4. However, sequence comparisons with other OATPs indicate that this skate Oatp shares only approximately 40-50% amino acid identity with the liver-specific OATPs/Oatps and with human OATP-F. Further computer analysis revealed that the highest amino acid identities reside in the first external (78%) and internal loops (75%) and transmembrane domains 2 (76%), 3 (62%), 4 (70%), and 11 (64%). We propose that the conserved regions of the SLC21A transporter family may be critical structural determinants of substrate specificity and function.
有机溶质的细胞摄取在很大程度上是由一个称为OATPs（SLC21A）的膜转运蛋白基因家族介导的。为了研究SLC21A家族的结构决定因素和进化发展，我们从小斑鳐（Raja erinacea）的肝脏中克隆并对一个高表达的进化原始的Oatp进行了功能表征。获得了一个全长cDNA（2.3 kb），其编码一个689个氨基酸的蛋白质。这种新型鳐鱼Oatp的特性，包括组织表达、亚细胞定位、底物选择性、Na(+)依赖性和抑制剂选择性，总体上与肝脏特异性人类OATP-C和大鼠Oatp4相似。然而，与其他OATPs的序列比较表明，这种鳐鱼Oatp与肝脏特异性OATPs/Oatps以及人类OATP-F仅具有约40-50%的氨基酸同一性。进一步的计算机分析显示，最高的氨基酸同一性存在于第一个外部环（78%）和内部环（75%）以及跨膜结构域2（76%）、3（62%）、4（70%）和11（64%）中。我们提出，SLC21A转运蛋白家族的保守区域可能是底物特异性和功能的关键结构决定因素。
