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 295866973  29 QCSAVMNETSCYALDFNGTGYCEW--NYNGLGIDYQILAGPTFILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMIL 106
Cdd:cd17328    1 VAVLFLINLLNYMDRFTIAGVLPDiqSDFLIDDSLAGLLQTVFIISYMVLSPIFGYLGDRYNRKWILAVGILIWSAATLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973 107 QGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIFNWGIYGGYGIAFPVGRYITKlnfWNLGWRVCY 186
Cdd:cd17328   81 SSFAPNFWQLLLFRALVGIGEASYSPIAPTIIADLFPKEKRTRALGVFYFAIPLGSGLGYVVGGLVAQ---ATGGWRWAF 157

                        170       180       190
                 ....*....|....*....|....*....|.
gi 295866973 187 LGAGVLTVIMAALTGTTLREPERKAIGEGDR 217
Cdd:cd17328  158 RVTGVLGVLLAILLLLFVREPPRGAAEGGVM 188

Protein spinster and spinster homologs of the Major Facilitator Superfamily of transporters; The protein spinster family includes Drosophila protein spinster, its vertebrate homologs, and similar proteins. Humans contain three homologs called protein spinster homologs 1 (SPNS1), 2 (SPNS2), and 3 (SPNS3). Protein spinster and its homologs may be sphingolipid transporters that play central roles in endosomes and/or lysosomes storage. SPNS2 is also called sphingosine 1-phosphate (S1P) transporter and is required for migration of myocardial precursors. S1P is a secreted lipid mediator that plays critical roles in cardiovascular, immunological, and neural development and function. The spinster-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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  29 QCSAVMNETSCYALDFNGTGYCEW--NYNGLGIDYQILAGPTFILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMIL 106
Cdd:cd17328    1 VAVLFLINLLNYMDRFTIAGVLPDiqSDFLIDDSLAGLLQTVFIISYMVLSPIFGYLGDRYNRKWILAVGILIWSAATLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973 107 QGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIFNWGIYGGYGIAFPVGRYITKlnfWNLGWRVCY 186
Cdd:cd17328   81 SSFAPNFWQLLLFRALVGIGEASYSPIAPTIIADLFPKEKRTRALGVFYFAIPLGSGLGYVVGGLVAQ---ATGGWRWAF 157

                        170       180       190
                 ....*....|....*....|....*....|.
gi 295866973 187 LGAGVLTVIMAALTGTTLREPERKAIGEGDR 217
Cdd:cd17328  158 RVTGVLGVLLAILLLLFVREPPRGAAEGGVM 188

Major Facilitator Superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973   56 GLGIDYQILAGPTFILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLAT 135
Cdd:pfam07690  28 GISPTEIGLLLTLFSLGYALAQPLAGRLSDRFGRRRVLLIGLLLFALGLLLLLFASSLWLLLVLRVLQGLGAGALFPAAL 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  136 GIMSDIFPEDKRALVMAIFNWGIYGGYGIAFPVGRYITKLnfwnLGWRVCYLGAGVLTVIMAALTGTTLREPERKAIGEG 215
Cdd:pfam07690 108 ALIADWFPPEERGRALGLVSAGFGLGAALGPLLGGLLASL----FGWRAAFLILAILSLLAAVLLLLPRPPPESKRPKPA 183

                  ..
gi 295866973  216 DR 217
Cdd:pfam07690 184 EE 185

MdtL family multidrug efflux MFS transporter;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  79 FMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIFNwGI 158
Cdd:PRK10473  57 FAGKIADRSGRKPVAIPGAALFIIASLLCSLAETSSLFLAGRFLQGIGAGCCYVVAFAILRDTLDDRRRAKVLSLLN-GI 135

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 295866973 159 YGGYGIAFPVGRYITKLNFwnlGWRVCYLGAGVLTVIMAALTGTTLRE 206
Cdd:PRK10473 136 TCIIPVLAPVLGHLIMLKF---PWQSLFYTMAAMGILVLLLSLFILKE 180

Protein spinster and spinster homologs of the Major Facilitator Superfamily of transporters; The protein spinster family includes Drosophila protein spinster, its vertebrate homologs, and similar proteins. Humans contain three homologs called protein spinster homologs 1 (SPNS1), 2 (SPNS2), and 3 (SPNS3). Protein spinster and its homologs may be sphingolipid transporters that play central roles in endosomes and/or lysosomes storage. SPNS2 is also called sphingosine 1-phosphate (S1P) transporter and is required for migration of myocardial precursors. S1P is a secreted lipid mediator that plays critical roles in cardiovascular, immunological, and neural development and function. The spinster-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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  29 QCSAVMNETSCYALDFNGTGYCEW--NYNGLGIDYQILAGPTFILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMIL 106
Cdd:cd17328    1 VAVLFLINLLNYMDRFTIAGVLPDiqSDFLIDDSLAGLLQTVFIISYMVLSPIFGYLGDRYNRKWILAVGILIWSAATLL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973 107 QGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIFNWGIYGGYGIAFPVGRYITKlnfWNLGWRVCY 186
Cdd:cd17328   81 SSFAPNFWQLLLFRALVGIGEASYSPIAPTIIADLFPKEKRTRALGVFYFAIPLGSGLGYVVGGLVAQ---ATGGWRWAF 157

                        170       180       190
                 ....*....|....*....|....*....|.
gi 295866973 187 LGAGVLTVIMAALTGTTLREPERKAIGEGDR 217
Cdd:cd17328  158 RVTGVLGVLLAILLLLFVREPPRGAAEGGVM 188

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  69 FILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRA 148
Cdd:COG2814   54 YLLGAALGAPLAGRLADRFGRRRVLLLGLLLFALGSLLCALAPSLWLLLAARFLQGLGAGALFPAALALIADLVPPERRG 133

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 295866973 149 LVMAIFNWGIYGGYGIAFPVGRYITKLnfwnLGWRVCYLGAGVLTVIMAALTGTTLREPERKA 211
Cdd:COG2814  134 RALGLLGAGLGLGPALGPLLGGLLADL----FGWRWVFLVNAVLALLALLLLLRLLPESRPAA 192

Hexuronate transporter, Glucarate transporter, and similar transporters of the Major Facilitator Superfamily; This family is composed of predominantly bacterial transporters for hexuronate (ExuT), glucarate (GudP), galactarate (GarP), and galactonate (DgoT). They mediate the uptake of these compounds into the cell. They belong 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  69 FILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRA 148
Cdd:cd17319   47 FFLGYALFQVPGGWLLDRFGARKVLAVSMLLWSLFTALTGFATSLTSLYVLRFLLGVAEAGFFPGAIKALAEWFPARERG 126

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 295866973 149 LVMAIFNWGIYGGYGIAFPVGRYITKLnfwnLGWRVCYLGAGVLTVIMAALT 200
Cdd:cd17319  127 RATGLFNSGAPLGAAIGPPLSGWLLLL----FGWRWAFIIEGLLGLLLAVLW 174

benzoate transport; [Transport and binding proteins, Carbohydrates, organic alcohols, and acids]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973   69 FILIFTIAGV-----FMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFP 143
Cdd:TIGR00895  56 FLFSAGLIGMafgalFFGPLADRIGRRRVLLWSILLFSVFTLLCALATNVTQLLILRFLAGLGLGGLMPNLNALVSEYAP 135

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 295866973  144 EDKRALVMAIfnwgIYGGYGIAFPVGRYITKLNFWNLGWRVCYLGAGVLTVIMAALTGTTLREPERKAIGEGDR 217
Cdd:TIGR00895 136 KRFRGTAVGL----MFCGYPIGAAVGGFLAGWLIPVFGWRSLFYVGGIAPLLLLLLLMRFLPESIDFLVSKRPE 205

bacterial MdtG-like and eukaryotic solute carrier 18 (SLC18) family of the Major Facilitator Superfamily of transporters; This family is composed of eukaryotic solute carrier 18 (SLC18) family transporters and related bacterial multidrug resistance (MDR) transporters including several proteins from Escherichia coli such as multidrug resistance protein MdtG, from Bacillus subtilis such as multidrug resistance proteins 1 (Bmr1) and 2 (Bmr2), and from Staphylococcus aureus such as quinolone resistance protein NorA. The family also includes Escherichia coli arabinose efflux transporters YfcJ and YhhS. 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. The SLC18 transporter family includes vesicular monoamine transporters (VAT1 and VAT2), vesicular acetylcholine transporter (VAChT), and SLC18B1, which is proposed to be a vesicular polyamine transporter (VPAT). The MdtG/SLC18 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  72 IFTIAGVFM----GFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKR 147
Cdd:cd17325   39 AYALAQLLFsppaGRLSDRFGRKRLLLLGLLLLAVSTLLFAFATSYWQLLLARFLQGLASAAVWPAAMALIADIAPPEER 118

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 295866973 148 ALVMAIFNWGIYGGYGIAFPVGRYITKLnfwnLGWRVCYLGAGVLTVIMAALTGTTLREPERKA 211
Cdd:cd17325  119 GRAMGIFSSAIGLGFLIGPLLGGLLADA----LGYRAPFLVCAALALLALVLALLLLPEPRPPP 178

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 295866973  69 FILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRA 148
Cdd:cd06174   40 FSLGYALLQPLAGLLADRFGRRPVLLLGLLLFALGALLFAFAPSFWLLLLGRFLLGLGSGLIDPAVLALIADLFPERERG 119

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 295866973 149 LVMAIFNWGIYGGYGIAFPVGRYITKLNFWnlGWRVCYLGAGVLTVIMAALTGTTLREPERKA 211
Cdd:cd06174  120 RALGLLQAFGSVGGILGPLLGGILASSLGF--GWRAVFLIAAALALLAAILLLLVVPDPPESA 180

Metazoan Synaptic vesicle glycoprotein 2 (SV2) and related small molecule transporters of the Major Facilitator Superfamily; This family is composed of metazoan synaptic vesicle glycoprotein 2 (SV2) and related small molecule transporters including those that transport inorganic phosphate (Pht), aromatic compounds (PcaK and related proteins), proline/betaine (ProP), alpha-ketoglutarate (KgtP), citrate (CitA), shikimate (ShiA), and cis,cis-muconate (MucK), among others. SV2 is a transporter-like protein that serves as the receptor for botulinum neurotoxin A (BoNT/A), one of seven neurotoxins produced by the bacterium Clostridium botulinum. BoNT/A blocks neurotransmitter release by cleaving synaptosome-associated protein of 25 kD (SNAP-25) within presynaptic nerve terminals. Also included in this family is synaptic vesicle 2 (SV2)-related protein (SVOP) and similar proteins. SVOP is a transporter-like nucleotide binding protein that localizes to neurotransmitter-containing vesicles. The SV2-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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  75 IAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIF 154
Cdd:cd17316   51 IGALLFGYLGDRIGRKKALILTLLLFGLATLLIGLLPTPILLLVLRFLQGIGIGGEYPGASTYVAEFAPSKRRGFALGLL 130

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 295866973 155 NWGIYGGYGIAFPVGRYITKLNFWNLGWRVCYLGAGVLTVIMAALTGTTLR 205
Cdd:cd17316  131 QSGWALGALLAALVASLLIPLLSGDWGWRILFLIGALPALLALLLRRRTLL 181

Methylenomycin A resistance protein (also called MMR peptide) and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This family is composed of bacterial, fungal, and archaeal multidrug resistance (MDR) transporters including several proteins from Bacilli such as methylenomycin A resistance protein (also called MMR peptide), tetracycline resistance protein (TetB), and lincomycin resistance protein LmrB, as well as fungal proteins such as vacuolar basic amino acid transporters, which are involved in the transport into vacuoles of the basic amino acids histidine, lysine, and arginine in Saccharomyces cerevisiae, and aminotriazole/azole resistance proteins. 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 while TetB resistance to tetracycline by an active tetracycline efflux. MMR-like MDR transporters belong 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  69 FILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRA 148
Cdd:cd17321   40 YLLAFAALLLLAGRLGDRFGRKRVFLIGLALFGLASLLCALAPSLAFLIAARALQGIGAAAIMPASLALIAATFPGERRG 119

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 295866973 149 LVMAIfnWGIYGGYGIAF--PVGRYITklnfWNLGWRVCYLGAGVLTVIMAALT 200
Cdd:cd17321  120 RALGL--WGAVVGIGAALgpLLGGLLL----ELFGWRWIFLINVPIGLVALLLA 167

Methylenomycin A resistance protein (also called MMR peptide)-like multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This subfamily is composed of putative multidrug resistance (MDR) transporters including Chlamydia trachomatis antiseptic resistance protein QacA_2, and Serratia sp. DD3 Bmr3. 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. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  72 IFTIAGV----FMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGeSGCNPLATGIMSDIFPEDKR 147
Cdd:cd17504   39 AYLLVGAvstpILGRLGDLYGRKKVLLIVLAIYTAGSLLAAFAPNLPVLIAGRALQGIG-GAVFPLAFALVREEFPPERV 117

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 295866973 148 ALVMAIFNWGIYGGYGIAFPVGRYITKlnfwNLGWRVCYLGAGVLTVIMAALT 200
Cdd:cd17504  118 PVAQGILSATFGIGAGIGLPLGGWIVQ----HLGWRWIFWTAAPVAVLLAALV 166

Bacillus subtilis multidrug efflux protein YfmO and similar transporters of the Major Facilitator Superfamily; This family is composed of Bacillus subtilis multidrug efflux protein YfmO, bacillibactin exporter YmfD/YmfE, uncharacterized MFS-type transporter YvmA, and similar proteins. YfmO acts to efflux copper or a copper complex, and could contribute to copper resistance. YmfD/YmfE is involved in secretion of bacillibactin. The YfmO-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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  71 LIFTIAGVFMGFAA--------DKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIF 142
Cdd:cd17474  238 LLFAGWSVLLALGSlfvgrllkKRFGARRILVIGLLLYALSLLLLGFVPSLALLLIAIVLFGLGLGLNLPLLTTLVTELA 317

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 295866973 143 PEDKRALVMAIFNWGIYGGYGIAFPVGRYItklnFWNLGWRVCYLGAGVLTVIMAALT 200
Cdd:cd17474  318 PEEERGTASSLYNFVRFLGQAVGPLLFGLL----LEIFGLSAPFLVGAAIALAAAVLL 371

Saccharomyces cerevisiae Azole resistance protein 1 (Azr1p), and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This subfamily is composed of multidrug resistance (MDR) transporters including various Saccharomyces cerevisiae proteins such as azole resistance protein 1 (Azr1p), vacuolar basic amino acid transporter 1 (Vba1p), vacuolar basic amino acid transporter 5 (Vba5p), and Sge1p (also known as Nor1p, 10-N-nonyl acridine orange resistance protein, and crystal violet resistance protein). 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. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  81 GFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIFNwGIYG 160
Cdd:cd17502   51 GKLSDLFGRKWVLLIAIVIFELGSLLCGLAPNMTMLIVGRAIQGIGGGGLMSLAFIIIADLVPPRERGKYQGYIG-AVFG 129

                         90       100
                 ....*....|....*....|....*...
gi 295866973 161 GYGIAFP-VGRYITKlnfwNLGWRVCYL 187
Cdd:cd17502  130 IASVAGPlIGGAFTD----HLSWRWCFY 153

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  81 GFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIfnWGIYG 160
Cdd:cd17503   52 GWLADRFGTRRLFLTALALFTLGSLLCGLAPNLASLIIFRILQGFGGGVLIPLAQTILLRIYPPEKRGAAMGL--VGLVI 129

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 295866973 161 GYGIAF--PVGRYITKlnfwNLGWRVCYLGA---GVLTVIMAAL 199
Cdd:cd17503  130 LLAPAIgpTLGGWLTD----NLSWRWIFYINlpiGILALLLAPL 169

Cyanate permease [Inorganic ion transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  71 LIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPeDKRALV 150
Cdd:COG2807   64 LAFGLFAPLAPRLARRFGLERTLLLALLLLAAGLLLRSLAPSVALLLAGTALIGAGIAVGNVLLPGLIKRWFP-DRVGLM 142

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 295866973 151 MAIFNWGIYGGYGIAFPVGRYITKLnfwnLGWRVCYLGAGVLTVIMAALTGTTLREPERKA 211
Cdd:COG2807  143 TGLYTAAMGLGAALAAGLTVPLAAA----LGWRGALAVWALLALLALLLWLPLLRRRPAAA 199

Mycobacterium tuberculosis uncharacterized MFS-type transporter MT3072 and similar transporters of the Major Facilitator Superfamily; This family includes the Mycobacterium tuberculosis uncharacterized MFS-type transporter MT3072. It 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  75 IAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIF 154
Cdd:cd17475   46 VSMLPAGWLLDRFGERRVLAVGLLLMGAAALLMALVGSYPVLLVLLFLVGAGYGSVQPGGGRAIMRWFPPRERGLAMGIR 125

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 295866973 155 NWGIYGGYGIAFPVGRYItklnFWNLGWRVCYLGAGVLTVIMAALTGTTLREPERKA 211
Cdd:cd17475  126 QTGVPLGGALAAALLPPL----ALHYGWRAAFVVAGLVSILAAVLFWLFYREPPAAS 178

Cis,cis-muconate transport protein and similar proteins of the Major Facilitator Superfamily; This subfamily is composed of Acinetobacter sp. Cis,cis-muconate transport protein (MucK), Escherichia coli putative sialic acid transporter 1, and similar proteins. MucK functions in the uptake of muconate and allows Acinetobacter calcoaceticus ADP1 (BD413) to grow on exogenous cis,cis-muconate as the sole carbon source. The MucK subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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 295866973  68 TFILIFT-IAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDK 146
Cdd:cd17371   41 TVTLAGGaIGGILGGILADRFGRVRVLVITILLFAVFTLLCGFAQNYWQLLILRALAGLGFGGEWAAGAALMAEYVPARH 120

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 295866973 147 RALVMAIFNWGIYGGYGIAFPVGRYITKLNFWNLGWRVCYLgAGVLTVIMAALTGTTLREPER 209
Cdd:cd17371  121 RGKALGYVQSGWAVGWLLATLLAALLFPLLPPEIAWRVLFL-LGALPALLVLFIRRFVKEPPQ 182

Fungal Hexose transporter subfamily of the Major Facilitator Superfamily of transporters and similar proteins; The fungal hexose transporter (HXT) subfamily is comprised of functionally redundant proteins that function mainly in the transport of glucose, as well as other sugars such as galactose and fructose. Saccharomyces cerevisiae has 20 genes that encode proteins in this family (HXT1 to HXT17, GAL2, SNF3, and RGT2). Seven of these (HXT1-7) encode functional glucose transporters. Gal2p is a galactose transporter, while Rgt2p and Snf3p act as cell surface glucose receptors that initiate signal transduction in response to glucose, functioning in an induction pathway responsible for glucose uptake. Rgt2p is activated by high levels of glucose and stimulates expression of low affinity glucose transporters such as Hxt1p and Hxt3p, while Snf3p generates a glucose signal in response to low levels of glucose, stimulating the expression of high affinity glucose transporters such as Hxt2p and Hxt4p. Schizosaccharomyces pombe contains eight GHT genes (GHT1-8) belonging to this family. Ght1, Ght2, and Ght5 are high-affinity glucose transporters; Ght3 is a high-affinity gluconate transporter; and Ght6 high-affinity fructose transporter. The substrate specificities for Ght4, Ght7, and Ght8 remain undetermined. The HXT subfamily belongs to the Glucose transporter -like (GLUT-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 295866973  75 IAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQ-GTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAI 153
Cdd:cd17356   60 FGALISSFLSDRIGRKKSIQIGCVIYIIGAIIQvAAIGKWYQLIVGRIIAGLGVGFASVLVPVYQSEVAPKHIRGTLVSL 139

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 295866973 154 FNWGIYGGYGIAFPVGrYITKLNFWNLGWRV----CYLGAGVLTVIMAAL 199
Cdd:cd17356  140 YQLAITIGILVAYCIN-YGTHKLDGSAQWRIplglQIVWGLLLLIGMFFL 188

Fucose permease [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  73 FTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAG----ESGCNPLATgimsDIFPEDKRA 148
Cdd:COG0738   56 YLLASLPAGRLIDRFGYKRGLLLGLLLMALGLLLFALAPSYPLLLLALFLLGLGlgllDVAANPYVA----ALGPETAAS 131

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 295866973 149 LvMAIFNwGIYGGYGIAFP-VGRYITKLNfWNLGWRVCYLGAGVLTVIMAALTGTT 203
Cdd:COG0738  132 R-LNLLH-AFFSLGALLGPlLGGLLILLG-LSLSWHLPYLILAVLLLLLALLFLRS 184

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  75 IAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGeSGCNPLATGIMSDIFPEDKRALVMAIF 154
Cdd:cd17330   49 LASPLWGRLSDRYGRKPVLLLSLAGSAVSYVLLGLSRNLWLLFLARFLDGLT-GGNVSVAQAYIADITDEEERAKAFGII 127

                 ....*.
gi 295866973 155 N--WGI 158
Cdd:cd17330  128 SaaFGL 133

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 295866973   81 GFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIFNWGIYG 160
Cdd:TIGR00711  58 GWLAKRFGTRRLFLISTFAFTLGSLLCGVAPNLELMIIFRVIQGFGGGPLIPLSFSTLLNIYPPEKRGRAMAIWGLTVLV 137

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 295866973  161 GYGIAFPVGRYITKlnfwNLGWRVCYLG---AGVLTVIMAALTGTTLREPERKAI 212
Cdd:TIGR00711 138 APALGPTLGGWIIE----NYHWRWIFLInvpIGIIVVVVAFFILPRDKPAASENF 188

Nitrate/nitrite transporter NarK [Inorganic ion transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  69 FILIFTIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKE-YWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKR 147
Cdd:COG2223  250 FALLGALGRPLGGWLSDRIGGRRVLLIVFALMALGLLLLALALGsLWLFLVLFLLLGLALGGGNGAVFALVPDIFPTKNA 329

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 295866973 148 ALVMAIFNW-GIYGGYGIAFPVGRYITklnfWNLGWRVCYLGAGVLTVIMAALTGTTLREPERKA 211
Cdd:COG2223  330 GAVYGLVGAaGGLGGFLGPLLFGALLD----ATGSYTAAFLVFAVLALVALVLTLLLYRRPRRAA 390

Pantothenate transporter FEN2 and similar transporters of the Major Facilitator Superfamily; This family is composed of Saccharomyces cerevisiae pantothenate transporter FEN2 (or fenpropimorph resistance protein 2) and similar proteins from fungi and bacteria including fungal vitamin H transporter, allantoate permease, and high-affinity nicotinic acid transporter, as well as Pseudomonas putida phthalate transporter and nicotinate degradation protein T (nicT). These proteins are involved in the uptake into the cell of specific substrates such as pathothenate, biotin, allantoate, and nicotinic acid, among others. The FEN2-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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  92 MLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAIFNWGIYGGY----GIAFP 167
Cdd:cd17327   73 WLSVFIVLWGLLTLLTAAVKNFGGLIALRFFLGLFESGVFPGFILYLGMWYKREEQAKRIAFFYAAAGLGSifggLLAYG 152

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 295866973 168 VGRYITKLNFWnlGWRVCYLGAGVLTVIMAALTGTTLREPERKA 211
Cdd:cd17327  153 VFKILGVGGLA--GWRWLFIIEGLITIIIGLVIFFWLPDNPSKA 194

Glucose transporters (GLUTs) and other similar sugar transporters of the Major Facilitator Superfamily; This family is composed of glucose transporters (GLUTs) and other sugar transporters including fungal hexose transporters (HXT), bacterial xylose transporter (XylE), plant sugar transport proteins (STP) and polyol transporters (PLT), H(+)-myo-inositol cotransporter (HMIT), and similar proteins. GLUTs, also called Solute carrier family 2, facilitated glucose transporters (SLC2A), are a family of proteins that facilitate the transport of hexoses such as glucose and fructose. There are fourteen GLUTs found in humans; they display different substrate specificities and tissue expression. They have been categorized into three classes based on sequence similarity: Class 1 (GLUTs 1-4, 14); Class 2 (GLUTs 5, 7, 9, and 11); and Class 3 (GLUTs 6, 8, 10, 12, and HMIT). GLUT proteins are comprised of about 500 amino acid residues, possess a single N-linked oligosaccharide, and have 12 transmembrane segments. The GLUT-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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295866973  74 TIAGVFMGFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAGESGCNPLATGIMSDIFPEDKRALVMAI 153
Cdd:cd17315   48 AIGSLFGGPLADRFGRRKSLLIAAVLYVIGALLSALAPNVWVLIVGRFLLGLGVGLASVLVPLYISEIAPAKIRGALGTL 127

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 295866973 154 FNWGIYGGYGIAFPVGrYITKLNFWNlGWRVCYLGAGVLTVIMAAL 199
Cdd:cd17315  128 NQLMITFGILLAYLLG-LALSLSPPG-WWRLMFALAAVPALLQLLL 171

Multidrug resistance protein MdtG and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This subfamily is composed of Escherichia coli multidrug resistance protein MdtG, Streptococcus pneumoniae multidrug resistance efflux pump PmrA, and similar multidrug resistance (MDR) transporters from bacteria. 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. MdtG confers resistance to fosfomycin and deoxycholate. PmrA serves as an efflux pump for various substrates and is associated with fluoroquinolone resistance. MdtG-like MDR 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 295866973  62 QILAGPTFILIFTIAGVFM---GFAADKYNRVNMLTVCTVIFGIAMILQGTVKEYWQLVILRMIMAAgESGCNPLATGIM 138
Cdd:cd17391   35 ELWSGLAFSSTFLVSAIFSpiwGRLADRYGRKPMLLRASLGMAIVIGLMAFVTNVWQLLILRLLQGV-FSGYVPNATALI 113

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 295866973 139 SDIFPEDKRALVMAIFNWGIYGGYGIAFPVGRYITKLnfwnLGWRVCYLGAGVLTVIMAALT 200
Cdd:cd17391  114 ASQTPKEKSGWALGTLSTGVVAGTLIGPLLGGFLADL----FGIRNVFFITGGLLFLAFLLT 171