ArticlePloS one2015
Evolutionary Analysis and Classification of OATs, OCTs, OCTNs, and Other SLC22 Transporters: Structure-Function Implications and Analysis of Sequence Motifs.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Article
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- Recent Advances on the Regulations of Organic Anion Transporters.Pharmaceutics · 2024Review
- A neurotransmitter atlas ofeLife · 2024Article
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- Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier.Diseases (Basel, Switzerland) · 2024Review
- Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.Nature communications · 2024Article
- Inflammation and Organic Cation Transporters Novel (OCTNs).Biomolecules · 2024Review
- Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Structural basis of promiscuous substrate transport by Organic Cation Transporter 1.Nature communications · 2023Article
- Drug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions.Scientific reports · 2022Article
- Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma.Cancers · 2022Article
- Insights into the structure and function of the human organic anion transporter 1 in lipid bilayer membranes.Scientific reports · 2022Article
- Strategies for Successful Over-Expression of Human Membrane Transport Systems Using Bacterial Hosts: Future Perspectives.International journal of molecular sciences · 2022Review
- What If Not All Metabolites from the Uremic Toxin Generating Pathways Are Toxic? A Hypothesis.Toxins · 2022Review
- SLC22 Transporters in the Fly Renal System Regulate Response to Oxidative Stress In Vivo.International journal of molecular sciences · 2021Article
- Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis.NAR cancer · 2021Article
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The SLC22 family includes organic anion transporters (OATs), organic cation transporters (OCTs) and organic carnitine and zwitterion transporters (OCTNs). These are often referred to as drug transporters even though they interact with many endogenous metabolites and signaling molecules (Nigam, S.K., Nature Reviews Drug Discovery, 14:29-44, 2015). Phylogenetic analysis of SLC22 supports the view that these transporters may have evolved over 450 million years ago. Many OAT members were found to appear after a major expansion of the SLC22 family in mammals, suggesting a physiological and/or toxicological role during the mammalian radiation. Putative SLC22 orthologs exist in worms, sea urchins, flies, and ciona. At least six groups of SLC22 exist. OATs and OCTs form two Major clades of SLC22, within which (apart from Oat and Oct subclades), there are also clear Oat-like, Octn, and Oct-related subclades, as well as a distantly related group we term "Oat-related" (which may have different functions). Based on available data, it is arguable whether SLC22A18, which is related to bacterial drug-proton antiporters, should be assigned to SLC22. Disease-causing mutations, single nucleotide polymorphisms (SNPs) and other functionally analyzed mutations in OAT1, OAT3, URAT1, OCT1, OCT2, OCTN1, and OCTN2 map to the first extracellular domain, the large central intracellular domain, and transmembrane domains 9 and 10. These regions are highly conserved within subclades, but not between subclades, and may be necessary for SLC22 transporter function and functional diversification. Our results not only link function to evolutionarily conserved motifs but indicate the need for a revised sub-classification of SLC22.
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