Solute carriers (SLCs) are the largest family of transmembrane transporters in the human genome with more than 400 members. Despite the fact that SLCs mediate critical biological functions and several are important pharmacological targets, a large proportion of them is poorly characterized and present no assigned substrate. A major limitation to systems‐level de‐orphanization campaigns is the absence of a structured, language‐controlled chemical annotation. Here we describe a thorough manual annotation of SLCs based on literature. The annotation of substrates, transport mechanism, coupled ions, and subcellular localization for 446 human SLCs confirmed that ~30% of these were still functionally orphan and lacked known substrates. Application of a substrate‐based ontology to transcriptomic datasets identified SLC‐specific responses to external perturbations, while a machine‐learning approach based on the annotation allowed us to identify potential substrates for several orphan SLCs. The annotation is available at https://opendata.cemm.at/gsflab/slcontology/. Given the increasing availability of large biological datasets and the growing interest in transporters, we expect that the effort presented here will be critical to provide novel insights into the functions of SLCs.

中文翻译：

---

人类溶质载体的基于基质的本体。

溶质载体 (SLC) 是人类基因组中最大的跨膜转运蛋白家族，拥有 400 多个成员。尽管 SLC 介导关键的生物学功能并且其中一些是重要的药理学靶点，但其中很大一部分的特征很差，并且不存在指定的底物。系统级去孤儿化运动的一个主要限制是缺乏结构化的、语言控制的化学注释。在这里，我们描述了基于文献的 SLC 的彻底手动注释。对 446 个人类 SLC 的底物、转运机制、偶联离子和亚细胞定位的注释证实，其中约 30% 的 SLC 仍然是功能孤儿并且缺乏已知的底物。将基于底物的本体论应用于转录组数据集确定了 SLC 对外部扰动的特异性反应，而基于注释的机器学习方法使我们能够识别几个孤儿 SLC 的潜在底物。该注释可从 https://opendata.cemm.at/gsflab/slcontology/ 获取。鉴于大型生物数据集的可用性不断增加以及人们对转运蛋白的兴趣日益浓厚，我们预计这里提出的努力对于提供有关 SLC 功能的新见解至关重要。