ArticleThe Biochemical journal2021
Evolutionary rate covariation identifies SLC30A9 (ZnT9) as a mitochondrial zinc transporter.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Evolutionary Rate Covariation Across Malaria Parasite Species Enables Inference of Protein Interactions.Genome biology and evolution · 2026Article
- Zinc dyshomeostasis, mitochondrial dysfunction, and their pathological cycle in ischemic stroke pathophysiology: Mechanisms and potential therapeutic targets.Redox biology · 2026Review
- Lysosome-related organelles employ divergent mechanisms to modulate cytosolic zinc homeostasis.PLoS genetics · 2026Article
- Zinc as a master regulator of intracellular organelle homeostasis.Experimental & molecular medicine · 2026Review
- Evolutionary rate covariation across malaria parasite species enables inference of protein interactions.bioRxiv : the preprint server for biology · 2026Article
- PRDM1-driven SLC30A9 overexpression contributes to the malignant phenotype of cervical cancer cells via promoting mitochondrial hyperfunction.Cell death & disease · 2025Article
- Correlated Gene Copy Number Changes in a Seminal Fluid Protein Network inbioRxiv : the preprint server for biology · 2025Article
- ERC2.0 evolutionary rate covariation update improves inference of functional interactions across large phylogenies.Genome research · 2025Article
- Data- and knowledge-derived functional landscape of human solute carriers.Molecular systems biology · 2025Article
- ERC 2.0 - evolutionary rate covariation update improves inference of functional interactions across large phylogenies.bioRxiv : the preprint server for biology · 2025Article
- SLC30 (ZnT) and SLC39 (ZIP) zinc transporter families: from gatekeepers of zinc homeostasis to promoters of tumorigenesis and targets for clinical therapy.Frontiers in immunology · 2025Review
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- SLC30A9: an evolutionarily conserved mitochondrial zinc transporter essential for mammalian early embryonic development.Cellular and molecular life sciences : CMLS · 2024Article
- ZnT 9 Involvement in Estradiol-Modulated Zinc Homeostasis of the Human Follicular Microenvironment.Biological trace element research · 2024Article
- Unlocking the brain's zinc code: implications for cognitive function and disease.Frontiers in biophysics · 2024Article
- Human genetic adaptation related to cellular zinc homeostasis.PLoS genetics · 2023Article
- Review
- The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart.The Journal of general physiology · 2023Review
- Case report: Birk-Landau-Perez syndrome linked to theFrontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Recent advances in genome sequencing have led to the identification of new ion and metabolite transporters, many of which have not been characterized. Due to the variety of subcellular localizations, cargo and transport mechanisms, such characterization is a daunting task, and predictive approaches focused on the functional context of transporters are very much needed. Here we present a case for identifying a transporter localization using evolutionary rate covariation (ERC), a computational approach based on pairwise correlations of amino acid sequence evolutionary rates across the mammalian phylogeny. As a case study, we find that poorly characterized transporter SLC30A9 (ZnT9) coevolves with several components of the mitochondrial oxidative phosphorylation chain, suggesting mitochondrial localization. We confirmed this computational finding experimentally using recombinant human SLC30A9. SLC30A9 loss caused zinc mishandling in the mitochondria, suggesting that under normal conditions it acts as a zinc exporter. We therefore propose that ERC can be used to predict the functional context of novel transporters and other poorly characterized proteins.
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