biostudies-literatureUnknown25(10)Ferrada EEuropean Federation of Pharmaceutical Industries and AssociationsInnovative Medicines InitiativeHorizon 2020 Framework ProgrammeÖsterreichischen Akademie der WissenschaftenSolute carriers are an operationally defined diverse family of membrane proteins involved in the transport of nutrients, metabolites, xenobiotics, and drugs. Here, we provide an integrative classification of solute carriers by combining evolutionary information with proteome-wide structure models recently made available through the AlphaFold resource. Analyses of orthologous relations among 455 protein-coding genes currently classified as human solute carriers, over the fully sequenced genomes of 2,100 species, suggest no more than approximately 180 independent evolutionary origins. Structural comparative analyses provided further insight revealing a total of 24 structurally distinct transmembrane folds, increasing by approximately 40% the number of previously described SLC structural foldiScience105096https://www.ebi.ac.uk/biostudies/studies/S-EPMC9508557biostudies-literatureA structure and evolutionary-based classification of solute carriers.PMC9508557Ferrada ESuperti-Furga GfalseA structure and evolutionary-based classification of solute carriers.Solute carriers are an operationally defined diverse family of membrane proteins involved in the transport of nutrients, metabolites, xenobiotics, and drugs. Here, we provide an integrative classification of solute carriers by combining evolutionary information with proteome-wide structure models recently made available through the AlphaFold resource. Analyses of orthologous relations among 455 protein-coding genes currently classified as human solute carriers, over the fully sequenced genomes of 2,100 species, suggest no more than approximately 180 independent evolutionary origins. Structural comparative analyses provided further insight revealing a total of 24 structurally distinct transmembrane folds, increasing by approximately 40% the number of previously described SLC structural fold2022-01-01T00:00:00Z2022 Oct2026-05-28T03:30:26.349Z2025-02-19T00:43:46.692ZS-EPMC95085573616465110.1016/j.isci.2022.105096