A substrate‐based ontology for human solute carriers

Abstract

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.

A guide to plasma membrane solute carrier proteins

“…For more specific structural information for these protein families, the reader is referred to Bai et al [36]. A continuously updated resource containing similar information will be available through Meixner, Girardi et al [562].…”

Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies

“…There are six new members in the SLC22 family, including one in the SLC22A family and five in the atypical SLC22B subfamily (Synaptic Vesicle glycoprotein, SV) 21,31 (http://slc.bioparadigms.org/, https://opendata.cemm.at/gsflab/slcontology/) (Figure 1A). For the purposes of the phylogenetic tree generation, we included all 23 members of the SLC22A family and the five new members of the SLC22B subfamily.…”

“…There are six new members in the SLC22 family, including one in the SLC22A family and five in the atypical SLC22B subfamily (Synaptic Vesicle glycoprotein, SV) 21,31 (http://slc. biopa radig ms.org/, https://opend ata.cemm.at/gsfla b/slcon tolog y/) ( Figure 1A).…”

An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters

“…For each SLC, the localization at the plasma membrane, the electrogenicity and the main substrate class are annotated. Annotation information regarding localization and substrate was extracted from Meixner et al (2020) (updated by addition of SLC66 family), information regarding electrogenicity is referenced in Supplementary Table S1 and SLC fold was extracted from the Pfam database. (B) Transport mechanisms of SLCs.…”