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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911  90 LAFTVGSFLLSAITLPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYgasnPDSLSVLIFIALALNGFGGMCMTFTSLTLP 169
Cdd:cd06174   35 LLFALFSLGYALLQPLAGLLADRFGRRPVLLLGLLLFALGALLFAF----APSFWLLLLGRFLLGLGSGLIDPAVLALIA 110

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568972911 170 NMFGDLRSTF---IALMIGSYASSAVTFPGIKLIYDAGASFIGILVVWAGCSGLVFFNCFFNWPLEPFPGPED 239
Cdd:cd06174  111 DLFPERERGRalgLLQAFGSVGGILGPLLGGILASSLGFGWRAVFLIAAALALLAAILLLLVVPDPPESARAK 183

drug resistance transporter, EmrB/QacA subfamily; This subfamily of drug efflux proteins, a part of the major faciliator family, is predicted to have 14 potential membrane-spanning regions. Members with known activities include EmrB (multiple drug resistance efflux pump) in E. coli, FarB (antibacterial fatty acid resistance) in Neisseria gonorrhoeae, TcmA (tetracenomycin C resistance) in Streptomyces glaucescens, etc. In most cases, the efflux pump is described as having a second component encoded in the same operon, such as EmrA of E. coli. [Cellular processes, Toxin production and resistance, Transport and binding proteins, Other]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911   94 VGSFLLSAITlplGIIMDKYGPRKLRLLGSACFAVSCLLIAYGAsNPDSLSVLIFIALALNGFGGMC--MTFTSLTLPNM 171
Cdd:TIGR00711 302 LAPMLSSPIA---GRMGDKIDPRKLVTIGLILYAVGFYWRAFTF-TPDTPFLAIALPQFIRGFGMGCffMPLTTIALSGL 377

                          90
                  ....*....|..
gi 568972911  172 FGDLRSTFIALM 183
Cdd:TIGR00711 378 PPHKIARGSSLS 389

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911  90 LAFTVGSFLLSAITLPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYgasnPDSLSVLIFIALALNGFGGMCMTFTSLTLP 169
Cdd:cd06174   35 LLFALFSLGYALLQPLAGLLADRFGRRPVLLLGLLLFALGALLFAF----APSFWLLLLGRFLLGLGSGLIDPAVLALIA 110

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568972911 170 NMFGDLRSTF---IALMIGSYASSAVTFPGIKLIYDAGASFIGILVVWAGCSGLVFFNCFFNWPLEPFPGPED 239
Cdd:cd06174  111 DLFPERERGRalgLLQAFGSVGGILGPLLGGILASSLGFGWRAVFLIAAALALLAAILLLLVVPDPPESARAK 183

Bacillus subtilis lincomycin resistance protein (LmrB) and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This subfamily is composed of multidrug resistance (MDR) transporters including Bacillus subtilis lincomycin resistance protein LmrB, and several proteins from Escherichia coli such as the putative MDR transporters EmrB, MdtD, and YieQ. 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. For example, MMR confers resistance to the epoxide antibiotic methylenomycin. This subfamily belongs to the Methylenomycin A resistance protein (also called MMR peptide) and similar multidrug resistance (MDR) transporters (MMR-like MDR transporter) 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568972911  98 LLSAITLPL-GIIMDKYGPRKLRLLGSACFAVSCLLIAYgaSNPDSLSVLIFIALALNGFgGMCMTFTSLT 167
Cdd:cd17503  225 LASAILSPLvGRLLDKFGPRLLLLAGLLLLALGTLLLAF--LTPDTSLWLIILPLFIRGL-GMGLVFMPLN 292

Major Facilitator Superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911   88 LNLAFTVGSFLLSAITLPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYGASNPDSLSVLIFIALALNGFGGMCMTFTSLT 167
Cdd:pfam07690  34 IGLLLTLFSLGYALAQPLAGRLSDRFGRRRVLLIGLLLFALGLLLLLFASSLWLLLVLRVLQGLGAGALFPAALALIADW 113

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911  168 LPnmfGDLRSTFIALMIGSYASSAVTFPGIKLIYDAGASFIGILVVWAGCSGLVFFNCFF 227
Cdd:pfam07690 114 FP---PEERGRALGLVSAGFGLGAALGPLLGGLLASLFGWRAAFLILAILSLLAAVLLLL 170

Monocarboxylate transporter-homologous (Mch) 1 protein and similar transporters of the Major Facilitator Superfamily of transporters; Yeast monocarboxylate transporter-homologous (Mch) proteins are putative transporters that do not transport monocarboxylic acids across the plasma membrane, and may play roles distinct from their mammalian counterparts. Their function has not been determined. The Mch1p-like group belongs to the Monocarboxylate transporter -like (MCT-like) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911  86 EILNLAFtVGSFLLSAITLPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYGASNPD-SLSV-LIFIALALNGFGGMCMTF 163
Cdd:cd17354   38 QQNNLLS-VAKDLGYLVGPLLGLLSDRLGPWLLLLIGAILFFPGYGVLWLVVTGLIsDLSFwLMCLCFFLIGNSTSSLYT 116

                         90       100       110
                 ....*....|....*....|....*....|..
gi 568972911 164 TSLTLPN-MFGDLRSTFIALMIGSYASSAVTF 194
Cdd:cd17354  117 AALVTCAkNFPESRGLAIGIPKGCYGLSGAIG 148

Oxalate:formate antiporter (OFA) and similar proteins of the Major Facilitator Superfamily of transporters; This subfamily is composed of Oxalobacter formigenes oxalate:formate antiporter (OFA or OxlT) and similar proteins. O. formigenes, a commensal found in the gut of animals and humans, plays an important role in clearing dietary oxalate from the intestinal tract, which is carried out by OFA/OxlT, an anion transporter that facilitates the exchange of divalent oxalate with monovalent formate, the product of oxalate decarboxylation. This exchange generates an electrochemical proton gradient and is the source of energy for ATP synthesis in this cell. The OFA-like subfamily belongs to the Monocarboxylate transporter -like (MCT-like) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 568972911  90 LAFTVGSFLLSAITLPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYGASNP 140
Cdd:cd17353   42 LAFTLTIVFLAISAPFAGRLVDRGGPRKAILIGGILFGLGFILSAFAISLP 92

Escherichia coli YfcJ, YhhS, and similar transporters of the Major Facilitator Superfamily; This subfamily is composed of Escherichia coli membrane proteins, YfcJ and YhhS, Bacillus subtilis uncharacterized MFS-type transporter YwoG, and similar proteins. YfcJ and YhhS are putative arabinose efflux transporters. YhhS has been implicated glyphosate resistance. YfcJ-like arabinose efflux transporters belong to the bacterial MdtG-like and eukaryotic solute carrier 18 (SLC18) 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911  92 FTVGSFLLSAIT--LPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYGASnpdslSVLIFIALALNGFG------------ 157
Cdd:cd17489   35 LVVGLFTLAALLarPFAGRLLDRFGRKRLLLIGLLIFALATLLYLLATS-----VALLLVLRLIHGIGwgafttaaatlv 109

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568972911 158 -----------GMCMTFTSLTLPNMFGdlrstfiaLMIGSYASSAVTFPGIkLIYDAGASFIGILVVW 214
Cdd:cd17489  110 adiippsrrgeGIGYYGLATTLAMALG--------PALGLFLYQHLGFAVL-FIVAAVLALLALLLVF 168

Predicted arabinose efflux permease AraJ, MFS family [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911  90 LAFTVGSFLLSAITLPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYGasnpDSLSVLIFIALALNGFGGMCMTFTSLTLP 169
Cdd:COG2814   49 LVVTAYLLGAALGAPLAGRLADRFGRRRVLLLGLLLFALGSLLCALA----PSLWLLLAARFLQGLGAGALFPAALALIA 124

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568972911 170 NMF-GDLRSTFIALMIGSYASSAVTFPGIKLIYDAGASFIGILVVWAGCSGLVFFNCFFNWP 230
Cdd:COG2814  125 DLVpPERRGRALGLLGAGLGLGPALGPLLGGLLADLFGWRWVFLVNAVLALLALLLLLRLLP 186

Predicted arabinose efflux permease AraJ, MFS family [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972911  90 LAFTVGSFLLSAITLPLGIIMDKYGPRKLRLLGSACFAVSCLLIAYGASNPDSLSVLIFIALALNGFGGMCMTFTSLTLP 169
Cdd:COG2814  247 LLLALFGLGGVLGALLAGRLADRFGRRRLLLIGLLLLALGLLLLALAGSLWLLLLALFLLGFGFGLLFPLLQALVAELAP 326

                         90
                 ....*....|....*...
gi 568972911 170 nmfGDLRSTFIALMIGSY 187
Cdd:COG2814  327 ---PEARGRASGLYNSAF 341