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      A guide to plasma membrane solute carrier proteins

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          Abstract

          This review aims to serve as an introduction to the solute carrier proteins (SLC) superfamily of transporter proteins and their roles in human cells. The SLC superfamily currently includes 458 transport proteins in 65 families that carry a wide variety of substances across cellular membranes. While members of this superfamily are found throughout cellular organelles, this review focuses on transporters expressed at the plasma membrane. At the cell surface, SLC proteins may be viewed as gatekeepers of the cellular milieu, dynamically responding to different metabolic states. With altered metabolism being one of the hallmarks of cancer, we also briefly review the roles that surface SLC proteins play in the development and progression of cancer through their influence on regulating metabolism and environmental conditions.

          Abstract

          In this ‘A Guide to SLC proteins’, we focus on transporter proteins—known as solute carriers (SLCs)—expressed on the plasma membrane. We aim to provide a useful survey of how metabolites and ions are transported between the extracellular and intracellular milieus. With altered metabolism being one of the hallmarks of cancer, we also briefly review roles that surface SLCs play in the development and progression of cancer.

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          Most cited references561

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          On the origin of cancer cells.

          O WARBURG (1956)
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            UniProt: a worldwide hub of protein knowledge

            (2018)
            Abstract The UniProt Knowledgebase is a collection of sequences and annotations for over 120 million proteins across all branches of life. Detailed annotations extracted from the literature by expert curators have been collected for over half a million of these proteins. These annotations are supplemented by annotations provided by rule based automated systems, and those imported from other resources. In this article we describe significant updates that we have made over the last 2 years to the resource. We have greatly expanded the number of Reference Proteomes that we provide and in particular we have focussed on improving the number of viral Reference Proteomes. The UniProt website has been augmented with new data visualizations for the subcellular localization of proteins as well as their structure and interactions. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.
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              A genome-wide association study identifies novel risk loci for type 2 diabetes.

              Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. Markers with the most significant difference in genotype frequencies between cases of type 2 diabetes and controls were fast-tracked for testing in a second cohort. This identified four loci containing variants that confer type 2 diabetes risk, in addition to confirming the known association with the TCF7L2 gene. These loci include a non-synonymous polymorphism in the zinc transporter SLC30A8, which is expressed exclusively in insulin-producing beta-cells, and two linkage disequilibrium blocks that contain genes potentially involved in beta-cell development or function (IDE-KIF11-HHEX and EXT2-ALX4). These associations explain a substantial portion of disease risk and constitute proof of principle for the genome-wide approach to the elucidation of complex genetic traits.
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                Author and article information

                Contributors
                gsuperti@cemm.oeaw.ac.at
                Journal
                FEBS J
                FEBS J
                10.1111/(ISSN)1742-4658
                FEBS
                The Febs Journal
                John Wiley and Sons Inc. (Hoboken )
                1742-464X
                1742-4658
                18 September 2020
                May 2021
                : 288
                : 9 ( doiID: 10.1111/febs.v288.9 )
                : 2784-2835
                Affiliations
                [ 1 ] CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria
                [ 2 ] Center for Physiology and Pharmacology Medical University of Vienna Austria
                Author notes
                [*] [* ] Correspondence

                G. Superti‐Furga, CeMM – Research Center for Molecular Medicine, of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3, 1090 Vienna, Austria

                Tel: +43 1/40160 70 001

                E‐mail: gsuperti@ 123456cemm.oeaw.ac.at

                Author information
                https://orcid.org/0000-0002-0570-1768
                Article
                FEBS15531
                10.1111/febs.15531
                8246967
                32810346
                96f9b3bd-42e3-45c9-889d-6d090d6dca7f
                © 2020 The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 07 August 2020
                : 27 March 2020
                : 17 August 2020
                Page count
                Figures: 9, Tables: 2, Pages: 52, Words: 38992
                Funding
                Funded by: ERC AdG Game of Gates
                Award ID: ERC AdG 695214
                Categories
                A Guide To…
                A Guide To…
                Custom metadata
                2.0
                May 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:01.07.2021

                Molecular biology
                amino acids,cancer,cell surface,cellular metabolism,cellular transport,glucose,ph,physiology,plasma membrane,solute carrier transporter

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