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| SLC-41 | |
|---|---|
| Name | SLC41 |
| Altsymbols | MgtE-like |
| Chromosomal location | Varied |
| Protein length | Variable |
| Family | Solute carrier family 41 |
SLC-41. SLC-41 denotes a family of eukaryotic and prokaryotic magnesium-transporter homologs studied across model organisms and clinical cohorts, with findings reported in literature from groups at National Institutes of Health, Harvard University, University of Oxford, Max Planck Society, and Stanford University; research integrates methods from teams involved in projects at Wellcome Trust, Howard Hughes Medical Institute, European Molecular Biology Laboratory, and laboratories connected to Cold Spring Harbor Laboratory and Salk Institute.
SLC41 family proteins were first described in comparative screens alongside transporters characterized by researchers at University of Cambridge, Massachusetts Institute of Technology, Yale University, University of California, San Francisco, and Imperial College London; early functional annotation referenced studies from National Center for Biotechnology Information, UniProt, and consortia including the 1000 Genomes Project, ENCODE Project, and GTEx Consortium. Structural and phylogenetic analyses have been performed by groups associated with European Molecular Biology Laboratory-EBI, Broad Institute, Wellcome Sanger Institute, and investigators who previously worked on TRPM7, CNNM2, MGT2, and other divalent cation transporters.
SLC41 genes encode membrane proteins whose topology and sequence motifs were analyzed in comparative genomics studies at Cold Spring Harbor Laboratory, Max Planck Institute for Molecular Cell Biology and Genetics, and Institute of Molecular Biology (Austria) using tools from European Bioinformatics Institute, Pfam, InterPro, PROSITE, and databases curated by UniProt Consortium. Conserved transmembrane helices and signature residues were identified in alignments that included orthologs from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Rattus norvegicus, Danio rerio, and prokaryotic homologs in genomes sequenced by teams at JGI, Sanger Institute, and Human Microbiome Project. Cryo-electron microscopy and X-ray crystallography efforts by groups at Stanford University, University of California, Berkeley, and Max Planck Institute for Biophysical Chemistry resolved domains resembling the bacterial MgtE fold and revealed conserved glycine and aspartate motifs referenced in datasets from Protein Data Bank.
Functional assays performed in laboratories at Harvard Medical School, Johns Hopkins University, University of Pennsylvania, and University of California, Los Angeles indicate SLC41 proteins mediate magnesium and other divalent cation flux, with electrophysiology, isotopic flux, and fluorescence approaches paralleling studies of TRPM6, TRPM7, CNNM3, and MgtE. Mechanistic models informed by molecular dynamics simulations from groups at Princeton University, ETH Zurich, and Columbia University propose alternating-access and channel-like behaviors influenced by intracellular nucleotides and membrane potential, complementing biochemical data from labs at Max Planck Institute, Institut Pasteur, and The Francis Crick Institute.
Transcriptomic and proteomic atlases produced by the GTEx Consortium, Human Protein Atlas, ENCODE Project, and research groups at Karolinska Institutet, University of Tokyo, Seoul National University, and Peking University show varied expression of SLC41 paralogs in tissues including kidney, brain, heart, pancreas, and immune organs; expression patterns correlate with datasets from Allen Institute for Brain Science and developmental atlases from Eurexpress. Single-cell studies from teams at Broad Institute and Harvard Stem Cell Institute detected cell-type specific expression in neuronal subpopulations, renal epithelia, and pancreatic islets, echoing functional links found in studies involving Insulinoma models and nephron studies led at Mount Sinai School of Medicine.
Variants and copy-number alterations in SLC41 family members have been reported in cohorts assembled by The Cancer Genome Atlas, ClinVar, Deciphering Developmental Disorders project, and clinical genetics centers at Mayo Clinic, Cleveland Clinic, and Great Ormond Street Hospital; associations include hypomagnesemia, neurological phenotypes, cardiac arrhythmias, and links investigated in studies of Type 2 diabetes mellitus, epilepsy, long QT syndrome, and kidney disorders. Functional follow-up performed by translational teams at Vanderbilt University Medical Center, University of Cambridge Addenbrooke's Hospital, and pharmaceutical collaborators evaluated pathogenic missense mutations and their impact on ion homeostasis.
Drug discovery programs at Pfizer, Novartis, GlaxoSmithKline, Roche, and academic groups at Yale School of Medicine and Imperial College London have screened small molecules and monoclonal antibodies for modulation of SLC41 activity, leveraging high-throughput platforms developed with partners including Illumina and Thermo Fisher Scientific. Preclinical studies employing rodent models from laboratories at Scripps Research and intervention trials coordinated with National Institute of Diabetes and Digestive and Kidney Diseases explored magnesium supplementation, allosteric modulators, and gene-therapy approaches analogous to efforts targeting CFTR and PCSK9.
Phylogenetic reconstructions using genomes sequenced by Broad Institute, Wellcome Sanger Institute, and Earth BioGenome Project place SLC41 homologs across Bacteria, Archaea, and Eukaryota, with conserved domains traced to bacterial MgtE ancestors; evolutionary studies were contributed by researchers at University of Edinburgh, University of California, Santa Cruz, University of Copenhagen, and National Taiwan University. Comparative analyses highlight lineage-specific expansions in vertebrates paralleling diversification events cataloged by the Ensembl and NCBI RefSeq projects and cross-referenced with functional studies in model organisms including Xenopus laevis and Arabidopsis thaliana.
Category:Solute carrier family