The SLCO (former SLC21) superfamily of transporters.
The SLCO (former SLC21) superfamily of transporters.
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DOI：
10.1016/j.mam.2012.10.009
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发表时间：
2013-04
影响因子：
10.6
通讯作者：
Stieger, Bruno
中科院分区：
文献类型：
--
作者：
Hagenbuch, Bruno;Stieger, Bruno
有机阴离子转运多肽超家族（OATP）的成员被分类在SLCO溶质载体家族内。预测所有功能良好表征的成员具有12个跨膜结构域，并且是介导广泛的内源性以及外源性物质的转运的钠非依赖性转运系统。底物主要是分子量大于300 Da的两亲性有机阴离子，但一些已知的传输底物也是中性的，甚至带正电荷。在充分表征的底物中有许多药物，包括他汀类药物、血管紧张素转化酶抑制剂、血管紧张素受体阻断剂、抗生素、抗组胺药、抗高血压药和抗癌药。基于它们的氨基酸序列同一性，不同的OATP聚类成家族（通常具有超过40%的氨基酸序列同一性）和亚家族（超过60%的氨基酸同一性）。通过对不同物种的基因组进行测序和对编码蛋白质的计算机预测，可以在数据库中找到300多种OATP，但在人类、啮齿动物和一些对药物研究重要的其他物种中，如恒河猴（Macaca mulatta）、狗（Canis lupus familiaris）和猪（Sus scrofa）中，只有一小部分OATP被鉴定出来。这些OATPs组成6个家族（OATP1-OATP6）和13个亚家族。本文就OATPs的内源性底物、组织分布、转运机制、表达调控、结构与功能的关系以及突变和多态性等方面的研究进展作一综述。
The members of the organic anion transporting polypeptide superfamily (OATPs) are classified within the SLCO solute carrier family. All functionally well characterized members are predicted to have 12 transmembrane domains and are sodium-independent transport systems that mediate the transport of a broad range of endo- as well as xenobiotics. Substrates are mainly amphipathic organic anions with a molecular weight of more than 300 Da, but some of the known transported substrates are also neutral or even positively charged. Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs. Based on their amino acid sequence identities, the different OATPs cluster into families (in general with more than 40% amino acid sequence identity) and subfamilies (more than 60% amino acid identity). With the sequencing of genomes from different species and the computerized prediction of encoded proteins more than 300 OATPs can be found in the databases, however only a fraction of them have been identified in humans, rodents, and some additional species important for pharmaceutical research like the rhesus monkey (Macaca mulatta), the dog (Canis lupus familiaris) and the pig (Sus scrofa). These OATPs form 6 families (OATP1–OATP6) and 13 subfamilies. In this review we try to summarize what is currently known about OATPs with respect to endogenous substrates, tissue distribution, transport mechanisms, regulation of expression, structure-function relationship and mutations and polymorphisms.
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