{"metadata":{"accession":"cd17386","entry_id":null,"type":"domain","go_terms":null,"source_database":"cdd","member_databases":null,"integrated":null,"hierarchy":null,"name":{"name":"Solute carrier 46 (SLC46) family of the Major Facilitator Superfamily of transporters","short":"MFS_SLC46"},"description":[{"text":"<p>The solute carrier 46 (SLC46) family is composed of three vertebrate members (SLC46A1, SLC46A2, and SLC46A3) and similar proteins from insects and nematodes. The best-studied member is SLC46A1, also called proton-coupled folate transporter (PCFT), which functions both as an intestinal proton-coupled high-affinity folate transporter involved in the absorption of folates and as an intestinal heme transporter which mediates heme uptake. SLC46A2, also called thymic stromal cotransporter protein (TSCOT), is a putative 12-transmembrane protein mainly expressed in the thymic cortex in a specific thymic epithelial cell (TEC) subpopulation. SLC46A3 is a lysosomal membrane protein that functions as a direct transporter of noncleavable antibody maytansine-based catabolites from the lysosome to the cytoplasm. The SLC46 family belongs to the Eukaryotic Solute carrier 46 (SLC46)/Bacterial Tetracycline resistance (TetA) -like (SLC46/TetA-like) family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement. [[cite:PUB00140723], [cite:PUB00140724], [cite:PUB00140725], [cite:PUB00140726], [cite:PUB00140727], [cite:PUB00140728], [cite:PUB00140729], [cite:PUB00140730], [cite:PUB00140731], [cite:PUB00140732], [cite:PUB00140733], [cite:PUB00140734], [cite:PUB00140668], [cite:PUB00140669], [cite:PUB00140672], [cite:PUB00096970], [cite:PUB00102174], [cite:PUB00075603], [cite:PUB00094019], [cite:PUB00097058], [cite:PUB00102173]]</p>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00075603":{"PMID":26098515,"ISBN":null,"volume":"44","issue":null,"year":2015,"title":"Structural Biology of the Major Facilitator Superfamily Transporters.","URL":null,"raw_pages":"257-83","medline_journal":"Annu Rev Biophys","ISO_journal":"Annu Rev Biophys","authors":["Yan N."],"DOI_URL":"http://dx.doi.org/10.1146/annurev-biophys-060414-033901"},"PUB00094019":{"PMID":23530251,"ISBN":null,"volume":"110","issue":"15","year":2013,"title":"Evolutionary mix-and-match with MFS transporters.","URL":null,"raw_pages":"5870-4","medline_journal":"Proc Natl Acad Sci U S A","ISO_journal":"Proc. Natl. Acad. Sci. U.S.A.","authors":["Madej MG","Dang S","Yan N","Kaback HR."],"DOI_URL":null},"PUB00140724":{"PMID":24745983,"ISBN":null,"volume":"73","issue":null,"year":2014,"title":"Biology of the major facilitative folate transporters SLC19A1 and SLC46A1.","URL":null,"raw_pages":"175-204","medline_journal":"Curr Top Membr","ISO_journal":"Curr Top Membr","authors":["Hou Z","Matherly LH."],"DOI_URL":null},"PUB00140668":{"PMID":26013383,"ISBN":null,"volume":"38","issue":"6","year":2015,"title":"Expression Analyses Revealed Thymic Stromal Co-Transporter/Slc46A2 Is in Stem Cell Populations and Is a Putative Tumor Suppressor.","URL":null,"raw_pages":"548-61","medline_journal":"Mol Cells","ISO_journal":"Mol Cells","authors":["Kim KY","Lee G","Yoon M","Cho EH","Park CS","Kim MG."],"DOI_URL":null},"PUB00140728":{"PMID":18823045,"ISBN":null,"volume":"98","issue":"5","year":2009,"title":"Molecular and functional characteristics of proton-coupled folate transporter.","URL":null,"raw_pages":"1608-16","medline_journal":"J Pharm Sci","ISO_journal":"J Pharm Sci","authors":["Yuasa H","Inoue K","Hayashi Y."],"DOI_URL":null},"PUB00140734":{"PMID":27530302,"ISBN":null,"volume":"100","issue":"5","year":2016,"title":"Lysosomal solute carrier transporters gain momentum in research.","URL":null,"raw_pages":"431-436","medline_journal":"Clin Pharmacol Ther","ISO_journal":"Clin Pharmacol Ther","authors":["Bissa B","Beedle AM","Govindarajan R."],"DOI_URL":null},"PUB00140732":{"PMID":20805364,"ISBN":null,"volume":"116","issue":"24","year":2010,"title":"Functional roles of aspartate residues of the proton-coupled folate transporter (PCFT-SLC46A1); a D156Y mutation causing hereditary folate malabsorption.","URL":null,"raw_pages":"5162-9","medline_journal":"Blood","ISO_journal":"Blood","authors":["Shin DS","Min SH","Russell L","Zhao R","Fiser A","Goldman ID."],"DOI_URL":null},"PUB00140669":{"PMID":23719032,"ISBN":null,"volume":"14","issue":"6","year":2013,"title":"Differential lineage specification of thymic epithelial cells from bipotent precursors revealed by TSCOT promoter activities.","URL":null,"raw_pages":"401-6","medline_journal":"Genes Immun","ISO_journal":"Genes Immun","authors":["Park CS","Lee G","Yang SJ","Ahn S","Kim KY","Shin H","Kim MG."],"DOI_URL":null},"PUB00097058":{"PMID":23403214,"ISBN":null,"volume":"38","issue":"3","year":2013,"title":"Structural advances for the major facilitator superfamily (MFS) transporters.","URL":null,"raw_pages":"151-9","medline_journal":"Trends Biochem Sci","ISO_journal":"Trends Biochem Sci","authors":["Yan N."],"DOI_URL":null},"PUB00140725":{"PMID":24396145,"ISBN":null,"volume":"42","issue":"4","year":2014,"title":"The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer.","URL":null,"raw_pages":"632-49","medline_journal":"Drug Metab Dispos","ISO_journal":"Drug Metab Dispos","authors":["Matherly LH","Wilson MR","Hou Z."],"DOI_URL":null},"PUB00140726":{"PMID":24383099,"ISBN":null,"volume":"13","issue":"6","year":2013,"title":"The proton-coupled folate transporter: physiological and  pharmacological roles.","URL":null,"raw_pages":"875-80","medline_journal":"Curr Opin Pharmacol","ISO_journal":"Curr Opin Pharmacol","authors":["Zhao R","Goldman ID."],"DOI_URL":null},"PUB00102173":{"PMID":18537473,"ISBN":null,"volume":"62","issue":null,"year":2008,"title":"Ins and outs of major facilitator superfamily antiporters.","URL":null,"raw_pages":"289-305","medline_journal":"Annu Rev Microbiol","ISO_journal":"Annu Rev Microbiol","authors":["Law CJ","Maloney PC","Wang DN."],"DOI_URL":null},"PUB00102174":{"PMID":26234418,"ISBN":null,"volume":"24","issue":"10","year":2015,"title":"Energy coupling mechanisms of MFS transporters.","URL":null,"raw_pages":"1560-79","medline_journal":"Protein Sci","ISO_journal":"Protein Sci","authors":["Zhang XC","Zhao Y","Heng J","Jiang D."],"DOI_URL":null},"PUB00140672":{"PMID":18392855,"ISBN":null,"volume":"123","issue":"5","year":2008,"title":"Polymorphisms in 9q32 and TSCOT are linked to cervical cancer in affected sib-pairs with high mean age at diagnosis.","URL":null,"raw_pages":"437-43","medline_journal":"Hum Genet","ISO_journal":"Hum Genet","authors":["Engelmark MT","Ivansson EL","Magnusson JJ","Gustavsson IM","Wyoni PI","Ingman M","Magnusson PK","Gyllensten UB."],"DOI_URL":null},"PUB00140723":{"PMID":27664775,"ISBN":null,"volume":"53","issue":null,"year":2017,"title":"The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption.","URL":null,"raw_pages":"57-72","medline_journal":"Mol Aspects Med","ISO_journal":"Mol Aspects Med","authors":["Zhao R","Aluri S","Goldman ID."],"DOI_URL":null},"PUB00140733":{"PMID":26631267,"ISBN":null,"volume":"75","issue":"24","year":2015,"title":"SLC46A3 Is Required to Transport Catabolites of Noncleavable Antibody Maytansine Conjugates from the Lysosome to the Cytoplasm.","URL":null,"raw_pages":"5329-40","medline_journal":"Cancer Res","ISO_journal":"Cancer Res","authors":["Hamblett KJ","Jacob AP","Gurgel JL","Tometsko ME","Rock BM","Patel SK","Milburn RR","Siu S","Ragan SP","Rock DA","Borths CJ","O'Neill JW","Chang WS","Weidner MF","Bio MM","Quon KC","Fanslow WC."],"DOI_URL":null},"PUB00096970":{"PMID":26758938,"ISBN":null,"volume":"17","issue":"2","year":2016,"title":"Understanding transport by the major facilitator superfamily (MFS): structures pave the way.","URL":null,"raw_pages":"123-32","medline_journal":"Nat Rev Mol Cell Biol","ISO_journal":"Nat Rev Mol Cell Biol","authors":["Quistgaard EM","Low C","Guettou F","Nordlund P."],"DOI_URL":null},"PUB00140731":{"PMID":21333572,"ISBN":null,"volume":"103","issue":"1","year":2011,"title":"Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption.","URL":null,"raw_pages":"33-7","medline_journal":"Mol Genet Metab","ISO_journal":"Mol Genet Metab","authors":["Shin DS","Mahadeo K","Min SH","Diop-Bove N","Clayton P","Zhao R","Goldman ID."],"DOI_URL":null},"PUB00140730":{"PMID":23601781,"ISBN":null,"volume":"280","issue":"12","year":2013,"title":"The monomeric state of the proton-coupled folate transporter represents the functional unit in the plasma membrane.","URL":null,"raw_pages":"2900-15","medline_journal":"FEBS J","ISO_journal":"FEBS J","authors":["Duddempudi PK","Nakashe P","Blanton MP","Jansen M."],"DOI_URL":null},"PUB00140727":{"PMID":22954694,"ISBN":null,"volume":"13","issue":"14","year":2012,"title":"The human proton-coupled folate transporter: Biology and therapeutic applications to cancer.","URL":null,"raw_pages":"1355-73","medline_journal":"Cancer Biol Ther","ISO_journal":"Cancer Biol Ther","authors":["Desmoulin SK","Hou Z","Gangjee A","Matherly LH."],"DOI_URL":null},"PUB00140729":{"PMID":25053408,"ISBN":null,"volume":"289","issue":"36","year":2014,"title":"Substituted cysteine accessibility reveals a novel transmembrane 2-3 reentrant loop and functional role for transmembrane domain 2 in the human proton-coupled folate transporter.","URL":null,"raw_pages":"25287-95","medline_journal":"J Biol Chem","ISO_journal":"J Biol Chem","authors":["Wilson MR","Hou Z","Matherly LH."],"DOI_URL":null}},"set_info":{"accession":"cl28910","name":"MFS"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":0,"interactions":0,"matches":435,"pathways":0,"proteins":435,"proteomes":161,"sets":1,"structural_models":{"alphafold":396,"bfvd":0},"structures":0,"taxa":643},"entry_annotations":{},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":null}}