Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse group of secondary transporters that includes uniporters, symporters, and antiporters. MFS proteins facilitate the transport across cytoplasmic or internal membranes of a variety of substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides. They do so using the electrochemical potential of the transported substrates. Uniporters transport a single substrate, while symporters and antiporters transport two substrates in the same or in opposite directions, respectively, across membranes. MFS proteins are typically 400 to 600 amino acids in length, and the majority contain 12 transmembrane alpha helices (TMs) connected by hydrophilic loops. The N- and C-terminal halves of these proteins display weak similarity and may be the result of a gene duplication/fusion event. Based on kinetic studies and the structures of a few bacterial superfamily members, GlpT (glycerol-3-phosphate transporter), LacY (lactose permease), and EmrD (multidrug transporter), MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement. Bacterial members function primarily for nutrient uptake, and as drug-efflux pumps to confer antibiotic resistance. Some MFS proteins have medical significance in humans such as the glucose transporter Glut4, which is impaired in type II diabetes, and glucose-6-phosphate transporter (G6PT), which causes glycogen storage disease when mutated.

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gi 1063731725   5 MRFLLgnWPLMSSIIVYCILCLHETAYSEIFALWANSPRRYG-----------GLGIFFFQVFVYPLAKRLLGP 67
Cdd:cd17330   169 VLFFL--PPLRRLLLVYFLIALAFAGLESVFSLFLKDRFGFSpsqiglllalvGIAGILAQLLLIPRLAKRLGE 240

Eukaryotic Solute carrier 46 (SLC46) family, Bacterial Tetracycline resistance proteins, and similar proteins of the Major Facilitator Superfamily of transporters; This family is composed of the eukaryotic proteins MFSD9, MFSD10, MFSD14, and SLC46 family proteins, as well as bacterial multidrug resistance (MDR) transporters such as tetracycline resistance protein TetA and multidrug resistance protein MdtG. MDR transporters are drug/H+ antiporters (DHA) that mediate the efflux of a variety of drugs and toxic compounds, and confer resistance to these compounds. TetA proteins confer resistance to tetracycline while MdtG confers resistance to fosfomycin and deoxycholate. The Solute carrier 46 (SLC46) family is composed of three vertebrate members (SLC46A1, SLC46A2, and SLC46A3), the best-studied of which is SLC46A1, 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. MFSD10 facilitates the uptake of organic anions such as some non-steroidal anti-inflammatory drugs (NSAIDs) and confers resistance to such NSAIDs. The SLC46/TetA-like family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

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gi 1063731725   5 MRFLLgnWPLMSSIIVYCILCLHETAYSEIFALWANSPRRYG-----------GLGIFFFQVFVYPLAKRLLGP 67
Cdd:cd17330   169 VLFFL--PPLRRLLLVYFLIALAFAGLESVFSLFLKDRFGFSpsqiglllalvGIAGILAQLLLIPRLAKRLGE 240

Eukaryotic Solute carrier 46 (SLC46) family, Bacterial Tetracycline resistance proteins, and similar proteins of the Major Facilitator Superfamily of transporters; This family is composed of the eukaryotic proteins MFSD9, MFSD10, MFSD14, and SLC46 family proteins, as well as bacterial multidrug resistance (MDR) transporters such as tetracycline resistance protein TetA and multidrug resistance protein MdtG. MDR transporters are drug/H+ antiporters (DHA) that mediate the efflux of a variety of drugs and toxic compounds, and confer resistance to these compounds. TetA proteins confer resistance to tetracycline while MdtG confers resistance to fosfomycin and deoxycholate. The Solute carrier 46 (SLC46) family is composed of three vertebrate members (SLC46A1, SLC46A2, and SLC46A3), the best-studied of which is SLC46A1, 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. MFSD10 facilitates the uptake of organic anions such as some non-steroidal anti-inflammatory drugs (NSAIDs) and confers resistance to such NSAIDs. The SLC46/TetA-like family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1063731725   5 MRFLLgnWPLMSSIIVYCILCLHETAYSEIFALWANSPRRYG-----------GLGIFFFQVFVYPLAKRLLGP 67
Cdd:cd17330   169 VLFFL--PPLRRLLLVYFLIALAFAGLESVFSLFLKDRFGFSpsqiglllalvGIAGILAQLLLIPRLAKRLGE 240