Organic anion transporting polypeptides of the OATP/SLC21 family:: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties
Organic anion transporting polypeptides of the OATP/SLC21 family:: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties
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DOI：
10.1007/s00424-003-1168-y
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发表时间：
2004-02-01
影响因子：
4.5
通讯作者：
Meier, PJ
中科院分区：
文献类型：
--
作者：
Hagenbuch, B;Meier, PJ
有机阴离子转运多肽(啮齿目：OATPs，人类：OATPs)形成了一个钠非依赖性转运系统的超家族，它介导了广泛的两亲性内源和外源有机化合物的跨膜转运。由于传统的SLC21基因分类不允许对基因和基因产物进行明确和物种独立的鉴定，所有OATPs/OATP都被重新归类到OATP/SLCO超家族中，并根据它们的系统发生关系和鉴定年代将其细分为家族(大于或等于40%的氨基酸序列同源性)、亚家族(大于或等于60%的氨基酸序列同源性)以及单个基因和基因产物。这一新的分类和命名系统的实施与雨果基因命名委员会(HGNC)达成了一致。在OATP/SLCO超家族的52个成员中，到目前为止已在人类、大鼠和小鼠中发现了36个成员。后者聚集在6个科(OATP1-OATP6)和13个亚科内。OATPs/OATPs代表12个跨膜结构域蛋白，含有超家族标志D-X-RW-(I，V)-GAWW-X-G-(F，L)-L。尽管物种多样性、多特异性和广泛的组织分布是许多OATPs/OATPs的共同特征，但OATP/SLCO超家族的一些成员在进化过程中高度保守，具有高度的底物特异性，并在不同的器官中表现出独特的细胞表达。因此，尽管具有广泛底物专一性的OATPs/OATPs似乎在许多外源两亲性有机阴离子化合物的生物利用度、分布和排泄中发挥着重要作用，但具有较窄转运底物谱的OATPs/OATPs可能在不同的器官中表现出更特定的生理功能。
The organic anion transporting polypeptides (rodents: Oatps, human: OATPs) form a superfamily of sodium-independent transport systems that mediate the transmembrane transport of a wide range of amphipathic endogenous and exogenous organic compounds. Since the traditional SLC21 gene classification does not permit an unequivocal and species-independent identification of genes and gene products, all Oatps/OATPs are newly classified within the OATP/SLCO superfamily and subdivided into families (greater than or equal to40% amino acid sequence identity), subfamilies (greater than or equal to60% amino acid sequence identity) and individual genes and gene products according to their phylogenetic relationships and chronology of identification. Implementation of this new classification and nomenclature system occurs in agreement with the HUGO Gene Nomenclature Committee (HGNC). Among 52 members of the OATP/SLCO superfamily, 36 members have been identified so far in humans, rat and mouse. The latter are clustered within 6 (out of 12) families (OATP1-OATP6) and 13 subfamilies. Oatps/OATPs represent 12 transmembrane domain proteins and contain the superfamily signature D-X-RW-(I,V)-GAWW-X-G-(F,L)-L. Although species divergence, multispecificity and wide tissue distribution are common characteristics of many Oatps/OATPs, some members of the OATP/SLCO superfamily are highly conserved during evolution, have a high substrate specificity and exhibit unique cellular expression in distinct organs. Hence, while Oatps/OATPs with broad substrate specificity appear to play an important role in the bioavailability, distribution and excretion of numerous exogenous amphipathic organic anionic compounds, Oatps/OATPs with a narrow spectrum of transport substrates may exhibit more specific physiological functions in distinct organs.