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 497477958   1 FFLFIGFYISLTTLPIYILDdLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd17489    6 FFFFLSFYLLLPVLPLYAHD-LGGSEAVAGLVVGLFTLAALLARPFAGRLLDRFGRKRLLLIGLLIFALATLLYLLATSV 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17489   85 ALLLVLRLIHGIGWGAFTTAAATLVADIIPPSRRGEGIGYYGLATT 130

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 497477958   1 FFLFIGFYISLTTLPIYILDdLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd17489    6 FFFFLSFYLLLPVLPLYAHD-LGGSEAVAGLVVGLFTLAALLARPFAGRLLDRFGRKRLLLIGLLIFALATLLYLLATSV 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17489   85 ALLLVLRLIHGIGWGAFTTAAATLVADIIPPSRRGEGIGYYGLATT 130

Major Facilitator Superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497477958    1 FFLFIGFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:pfam07690   6 FLAALGRSLLGPALPLLLAEDLGISPTEIGLLLTLFSLGYALAQPLAGRLSDRFGRRRVLLIGLLLFALGLLLLLFASSL 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 497477958   81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:pfam07690  86 WLLLVLRVLQGLGAGALFPAALALIADWFPPEERGRALGLVSAGFG 131

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 497477958   54 IGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYA 122
Cdd:TIGR00895  79 IGRRRVLLWSILLFSVFTLLCALATNVTQLLILRFLAGLGLGGLMPNLNALVSEYAPKRFRGTAVGLMF 147

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 497477958   1 FFLFIGFYISLTTLPIYILDdLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd17489    6 FFFFLSFYLLLPVLPLYAHD-LGGSEAVAGLVVGLFTLAALLARPFAGRLLDRFGRKRLLLIGLLIFALATLLYLLATSV 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17489   85 ALLLVLRLIHGIGWGAFTTAAATLVADIIPPSRRGEGIGYYGLATT 130

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 497477958   1 FFLFIGFYISLTTLPIYiLDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd17325    6 FLDMLGYGIIIPILPLY-AESLGASVAQIGLIVAAYALAQLLFSPPAGRLSDRFGRKRLLLLGLLLLAVSTLLFAFATSY 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17325   85 WQLLLARFLQGLASAAVWPAAMALIADIAPPEERGRAMGIFSSAIG 130

Major Facilitator Superfamily;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497477958    1 FFLFIGFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:pfam07690   6 FLAALGRSLLGPALPLLLAEDLGISPTEIGLLLTLFSLGYALAQPLAGRLSDRFGRRRVLLIGLLLFALGLLLLLFASSL 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 497477958   81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:pfam07690  86 WLLLVLRVLQGLGAGALFPAALALIADWFPPEERGRALGLVSAGFG 131

Na+/melibiose symporter or related transporter [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497477958   1 FFLFIGFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYF--TAD 78
Cdd:COG2211  238 LLFFLALALVAALLLYYFKYVLGLSAALVGLLLALYFLAALLGAPLWPRLAKRFGKKKAFIIGLLLAALGLLLLFflGPG 317

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 497477958  79 SLPMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFM 125
Cdd:COG2211  318 NLWLLLVLAALAGIGLGAILVLPWAMLADVVDYDEWKTGRRREGLYF 364

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 497477958   1 FFLFIGFYISLTTLPIyILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd17321    6 FLAALDVTIVNVALPT-IARDLGASPSQLQWVVNAYLLAFAALLLLAGRLGDRFGRKRVFLIGLALFGLASLLCALAPSL 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMF 124
Cdd:cd17321   85 AFLIAARALQGIGAAAIMPASLALIAATFPGERRGRALGLWGAV 128

Purine ribonucleoside efflux pump NepI and similar transporters of the Major Facilitator Superfamily; This family is composed of purine efflux pumps such as Escherichia coli NepI and Bacillus subtilis PbuE, sugar efflux transporters such as Corynebacterium glutamicum arabinose efflux permease, multidrug resistance (MDR) transporters such as Streptomyces lividans chloramphenicol resistance protein (CmlR), and similar proteins. NepI and PbuE are involved in the efflux of purine ribonucleosides such as guanosine, adenosine and inosine, as well as purine bases like guanine, adenine, and hypoxanthine, and purine base analogs. They play a role in the maintenance of cellular purine base pools, as well as in protecting the cells and conferring resistance against toxic purine base analogs such as 6-mercaptopurine. 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 NepI-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 497477958  25 SESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHGAGLGMATTATGAI 104
Cdd:cd17324   32 SVAQAGLLVSAYALGYALGALLLGPLSDRIERRRLLLVLLLLFILGNLLAALAPSFALLLLARALAGLAHGGFWAIAAAY 111

                         90       100
                 ....*....|....*....|..
gi 497477958 105 VADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17324  112 AADLVPPEKRGRAIGLVFSGLT 133

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 497477958   4 FIGFYISLTTLPI--YILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLP 81
Cdd:cd17474    9 LLAVLGVSIVDPIlpAIAEALGASPAQVGLLITAFTLPAAVLMPVAGVLADRFGRKKVLLPGLLLFGIGGLLCGLSDSFA 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 497477958  82 MLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17474   89 LLLAGRALQGIGAAGLGPLALTLIGDLFEGGERAKAMGLYEAALG 133

MFS family permease, includes anhydromuropeptide permease AmpG [Carbohydrate transport and metabolism, Amino acid transport and metabolism, Inorganic ion transport and metabolism, General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497477958   1 FFLFIGFYISLTTLPIyILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:COG0477   24 FLEGLDFTIVNVALPS-IAADLGASSAQLGWIVSAYLLGRAIGLLLFGRLGDRYGRKRVLLIGLLLFGLASLLCGLAPSP 102

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:COG0477  103 ELLIAARALQGIGAGGLMPGALALIAELFPARERGRALGLWGAAIG 148

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 497477958  12 TTLPIyILDDLKGSeSQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHG 91
Cdd:cd17502   17 TALPT-IVAEFGGL-SLVSWVGTAYLLTSTAFQPIYGKLSDLFGRKWVLLIAIVIFELGSLLCGLAPNMTMLIVGRAIQG 94

                         90       100
                 ....*....|....*....|....
gi 497477958  92 AGLGMATTATGAIVADIVPAERRG 115
Cdd:cd17502   95 IGGGGLMSLAFIIIADLVPPRERG 118

Sugar phosphate permease [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497477958   1 FFLFIGFYISLTTLPI---YILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTA 77
Cdd:COG2271   16 FLAYFLNYLDRSNLSVaapPLQADLGLSAAQLGLLASAFFLGYALGQIPAGLLADRFGRRRVLAIGLLLWGLATLLFGFA 95

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 497477958  78 DSLPMLLAVRLLHGAGLGMATTATGAIVADIVPAERRG 115
Cdd:COG2271   96 TSFWQLLLLRFLLGLGEAGFFPAALKLIAEWFPPKERG 133

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 497477958   1 FFLFIGFYISLTTLPIYILD--DLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTAD 78
Cdd:cd17330    6 FLDALGFGIVFPVLPFYVREfnKLGASGYYVGLLQSSYSLGQFLASPLWGRLSDRYGRKPVLLLSLAGSAVSYVLLGLSR 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 497477958  79 SLPMLLAVRLLHGAGLGMATTATgAIVADIVPAERRGEGEGY 120
Cdd:cd17330   86 NLWLLFLARFLDGLTGGNVSVAQ-AYIADITDEEERAKAFGI 126

Glucose transporter (GLUT) types 10 and 12, Class 3 GLUTs, and similar transporters of the Major Facilitator Superfamily; This subfamily is composed of glucose transporter type 10, GLUT12, plant polyol transporters (PLTs), 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. They belong 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 497477958   6 GFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLA 85
Cdd:cd17362   18 GALLSITSPALSGTDWYNLSSLQSGLVVSGSLLGALLGSLVAGALIDRLGRRKELILAALLYLVGSLVTGLAPSYPVLLV 97

                         90       100       110
                 ....*....|....*....|....*....|
gi 497477958  86 VRLLHGAGLGMATTATGAIVADIVPAERRG 115
Cdd:cd17362   98 GRLIYGVGIGLAMHAAPVYIAETSPSHIRG 127

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 497477958  21 DLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHGAGLGMATTA 100
Cdd:cd17315   28 GFGLSTSLQGLVVSSLLLGAAIGSLFGGPLADRFGRRKSLLIAAVLYVIGALLSALAPNVWVLIVGRFLLGLGVGLASVL 107

                         90
                 ....*....|....*
gi 497477958 101 TGAIVADIVPAERRG 115
Cdd:cd17315  108 VPLYISEIAPAKIRG 122

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 497477958   1 FFLFIGFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd06174    5 FFLTGLARGLISPLLPALLQSFGLSASQLGLLFALFSLGYALLQPLAGLLADRFGRRPVLLLGLLLFALGALLFAFAPSF 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd06174   85 WLLLLGRFLLGLGSGLIDPAVLALIADLFPERERGRALGLLQAFGS 130

YcaD and similar transporters of the Major Facilitator Superfamily; This family is composed of Escherichia coli MFS-type transporter YcaD, Bacillus subtilis MFS-type transporter YfkF, and similar proteins. They are uncharacterized transporters belonging 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 497477958   1 FFLFIGFYISLTTLPIyILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd17477    6 ALLGLGSGLLLPLLSL-RLEREGVSTALIGLVASAYYLGILLGSPLVPRLIRRVGHIRAFAAGAAITAVSVLLLALTDSP 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17477   85 WVWFLLRFVMGIGLAGLFVVSESWLNALATNENRGRVLGLYSTVLG 130

Multidrug resistance protein MdtH and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This family is composed of Escherichia coli MdtH and similar multidrug resistance (MDR) transporters from bacteria and archaea, many of which remain uncharacterized. 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. MdtH confers resistance to norfloxacin and enoxacin. MdtH-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 497477958  12 TTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHG 91
Cdd:cd17329  221 STLPVYVVEILGLGESLLGLLLALNALLIVLLQFPVARLVERFRLRKILMIGILLFAIGFAVLAFANTLAVLILAMIVLT 300

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 497477958  92 AGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd17329  301 LGEMLVFPAVQTLVAALAPPDKRGSYMGFYALAWG 335

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 497477958   1 FFLFIGFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMG-EIGCKKILMMSMVIFTVASALYFTADS 79
Cdd:cd06174  213 FLVNLAYYSFSTLLPLFLLDLGGLSVAVAGLLLSLFGLAGALGSLLLGLLSDrLIGRKPLLLIGLLLMALGLALLLLAPS 292

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  80 LPMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFM 125
Cdd:cd06174  293 LLLLLLLLLLLGFGLGGLLPLSFALIAELFPPEIRGTAFGLLNTFG 338

Sugar efflux transporter (Set) family of the Major Facilitator Superfamily of transporters; This family is composed of sugar transporters such as Escherichia coli Sugar efflux transporter SetA, SetB, SetC and other sugar transporters. SetA, SetB, and SetC are involved in the efflux of sugars such as lactose, glucose, IPTG, and substituted glucosides or galactosides. They may be involved in the detoxification of non-metabolizable sugar analogs. The Set 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 497477958   1 FFLFIGFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd17471  209 TLLFAANSMYIIAMPLYVTNELGGSESWVGLLFGLAAALEIPIMLLAGLLAKRFGKRRLLLAGFLAGVLFYLGLALATSL 288

                         90
                 ....*....|....*
gi 497477958  81 PMLLAVRLLHGAGLG 95
Cdd:cd17471  289 WQLIALQLLNAIFIG 303

Macrolide efflux protein A and similar proteins of the Major Facilitator Superfamily of transporters; This family is composed of Streptococcus pyogenes macrolide efflux protein A (MefA) and similar transporters, many of which remain uncharacterized. Some members may be multidrug resistance (MDR) transporters, which are drug/H+ antiporters (DHAs) that mediate the efflux of a variety of drugs and toxic compounds, conferring resistance to these compounds. MefA confers resistance to 14-membered macrolides including erythromycin and to 15-membered macrolides. It functions as an efflux pump to regulate intracellular macrolide levels. The MefA-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 497477958   1 FFLFIGFYISLttLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSL 80
Cdd:cd06173  220 FALLGGALTVL--LPLLAKEVLGGGAAGYGLLLAAFGVGALLGALLLGRLSKRRRRGRLLLIGALLLGLALLVLGLSPSL 297

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  81 PMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMFMT 126
Cdd:cd06173  298 WLLLAALFLLGLAGGLFNVPLNTLLQLRVPDELRGRVFSVYNALNS 343

Sugar phosphate permease [Carbohydrate transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497477958   1 FFLFIGFYISLTTLPIYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIG--CKKILMMSMVIFTVASALYFTAD 78
Cdd:COG2271  190 FLVYFALYGFLTWLPTYLVEVRGLSLAQAGLLLSLPFLAGIVGSLLGGWLSDRLGrrRKLVLAIGLLLAALALLLLALLP 269

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 497477958  79 SLPMLLAVRLLHGAGLGMATTATGAIVADIVPAERRGEGEGYYAMF 124
Cdd:COG2271  270 SPALAIALLFLAGFGLGGAFGLLWALAAELFPKKARGTASGLVNTF 315

Plant Polyol transporter family of the Major Facilitator Superfamily of transporters; The plant Polyol transporter (PLT) subfamily includes PLT1-6 from Arabidopsis thaliana and similar transporters. The best characterized member of the group is Polyol transporter 5, also called Sugar-proton symporter PLT5, which mediates the H+-symport of numerous substrates including linear polyols (such as sorbitol, xylitol, erythritol or glycerol), cyclic polyol myo-inositol, and different hexoses, pentoses (including ribose), tetroses, and sugar alcohols. It functions to transport a wide range of substrates into specific sink tissues in the plant. The PLT 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 497477958  16 IYILDDLKGSESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHGAGLG 95
Cdd:cd17437   21 IFIKEDLKISDVQEEVLIGSLNIISLVGSLAAGRTSDWIGRRYTIALAALIFFVGALLMGVAPNYPVLMVGRFVAGIGVG 100

                         90       100
                 ....*....|....*....|
gi 497477958  96 MATTATGAIVADIVPAERRG 115
Cdd:cd17437  101 FALMIAPVYTAEVAPASSRG 120

D-xylose-proton symporter and similar transporters of the Major Facilitator Superfamily; This subfamily includes bacterial transporters such as D-xylose-proton symporter (XylE or XylT), arabinose-proton symporter (AraE), galactose-proton symporter (GalP), major myo-inositol transporter IolT, glucose transport protein, putative metabolite transport proteins YfiG, YncC, and YwtG, and similar proteins. The symporters XylE, AraE, and GalP facilitate the uptake of D-xylose, arabinose, and galactose, respectively, across the boundary membrane with the concomitant transport of protons into the cell. IolT is involved in polyol metabolism and myo-inositol degradation into acetyl-CoA. The XylE-like 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 497477958  25 SESQVGLIISVFAITAVTSWPFTGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHGAGLGMATTATGAI 104
Cdd:cd17359   34 TPFLEGLVVSSALLGAAIGALFAGRLADRFGRRKTLLISAVLFFISALGSAFSPNFTIFIIARIIGGLAVGGASALVPMY 113

                         90
                 ....*....|.
gi 497477958 105 VADIVPAERRG 115
Cdd:cd17359  114 IAEVAPAEIRG 124

Escherichia coli inner membrane transport protein YajR and similar multidrug-efflux transporters of the Major Facilitator Superfamily; This family is composed of Escherichia coli inner membrane transport protein YajR and some uncharacterized multidrug-efflux transporters. YajR is a putative proton-driven major facilitator superfamily (MFS) transporter found in many gram-negative bacteria. Unlike most MFS transporters, YajR contains a C-terminal, cytosolic YAM domain, which may play an essential role for the proper functioning of the transporter. YajR-like 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 497477958   4 FIGFYISLTTLPIYILDDLKGSESQVGLIISVFAIT-AVTSWPFtGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPM 82
Cdd:cd17472    9 MLGMFLVLPVLSVYAKSLPGATPTLIGLALGIYGLTqAIFQIPF-GLLSDRIGRKPVILFGLLLFIAGSLLAAYATSIYG 87

                         90       100       110
                 ....*....|....*....|....*....|....
gi 497477958  83 LLAVRLLHGAGlgmATTATG-AIVADIVPAERRG 115
Cdd:cd17472   88 LILGRALQGSG---AISSVVmALLADLTREENRT 118

Multidrug transporter MdfA and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This family is composed of bacterial multidrug resistance (MDR) transporters including several proteins from Escherichia coli such as MdfA (also called chloramphenicol resistance pump Cmr), EmrD, MdtM, MdtL, bicyclomycin resistance protein (also called sulfonamide resistance protein), and the uncharacterized inner membrane transport protein YdhC. EmrD is a proton-dependent secondary transporter, first identified as an efflux pump for uncouplers of oxidative phosphorylation. It expels a range of drug molecules and amphipathic compounds across the inner membrane of E. coli. Similarly, MdfA is a secondary multidrug transporter that exports a broad spectrum of structurally and electrically dissimilar toxic compounds. These MDR transporters are drug/H+ antiporters (DHA) belonging 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 497477958  21 DLKGSESQVGLIISVFAI-TAVTSWPFtGKWMGEIGCKKILMMSMVIFTVASALYFTADSLPMLLAVRLLHGAGLGMATT 99
Cdd:cd17320   28 DLGASASAVQLTLSAYLLgFALGQLLY-GPLSDRFGRRPVLLAGLLLFILASLLCALASSIEQLLIARFLQGLGAAAGSV 106

                         90
                 ....*....|....*
gi 497477958 100 ATGAIVADIVPAERR 114
Cdd:cd17320  107 VARAIVRDLYSGAEL 121