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 52545721   1 MGSLGLFLQCAISLVFSLVMDRLVQRFGTRAVYLASVAAFPVAAGATCLSHSVAVVTASAALTGFTFSALQILPYTLASL 80
Cdd:cd17313 282 MGAWGLLIFSLAFLIFSLPIGKLGKKIGRKKVYLIGLVLFAVGMALMALVHNVTVALVLFALGGIGWATININPYPLVSD 361

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 52545721  81 YHREKqvflpkyrgdtggassedslmtsflpgpkpgapfpnghvgaggsgllppppalcgasacdvsvrvvvgeptearv 160
Cdd:cd17313 362 YHSES--------------------------------------------------------------------------- 366

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 52545721 161 vpGRGICLDLAILDSAFLLSQVAPSLFMGSI--VQLSQSVTAYMVSAAGLGLVAIYF 215
Cdd:cd17313 367 --GRGQGTDTGLLNLAISLAQILVSLLAGPIidVKGYGTVFPVAAVASFLSLVGALF 421

Solute carrier family 45 and similar sugar transporters of the Major Facilitator Superfamily of transporters; This group includes the solute carrier 45 (SLC45) family as well as plant sucrose transporters (SUCs or SUTs) and similar proteins such as Schizosaccharomyces pombe general alpha-glucoside permease. the SLC45 family is composed of four (A1-A4) vertebrate proteins as well as related insect proteins such as Drosophila sucrose transporter SCRT or Slc45-1. Members of this group transport sucrose and other sugars like maltose into the cell, with the concomitant uptake of protons (symport system). Plant sucrose transporters are crucial to carbon partitioning, playing a key role in phloem loading/unloading. They play a key role in loading and unloading of sucrose into the phloem and as a result, they control sucrose distribution throughout the whole plant and drive the osmotic flow system in the phloem. They also play a role in the exchange of sucrose between beneficial symbionts (mycorrhiza and Rhizobium) as well as pathogens such as nematodes and parasitic fungi. There are nine sucrose transporter genes in Arabidopsis and five in rice. Vertebrate SLC45 family proteins have been implicated in the regulation of glucose homoeostasis in the brain (SLC45A1), with skin and hair pigmentation (SLC45A2), and with prostate cancer and myelination (SLC45A3). Mutations in SLC45A2, also called MATP (membrane-associated transporter protein) or melanoma antigen AIM1, cause oculocutaneous albinism type 4 (OCA4), an autosomal recessive disorder of melanin biosynthesis that results in congenital hypopigmentation of ocular and cutaneous tissues. The SLC45 family and related sugar 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 52545721   1 MGSLGLFLQCAISLVFSLVMDRLVQRFGTRAVYLASVAAFPVAAGATCLSHSVAVVTASAALTGFTFSALQILPYTLASL 80
Cdd:cd17313 282 MGAWGLLIFSLAFLIFSLPIGKLGKKIGRKKVYLIGLVLFAVGMALMALVHNVTVALVLFALGGIGWATININPYPLVSD 361

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 52545721  81 YHREKqvflpkyrgdtggassedslmtsflpgpkpgapfpnghvgaggsgllppppalcgasacdvsvrvvvgeptearv 160
Cdd:cd17313 362 YHSES--------------------------------------------------------------------------- 366

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 52545721 161 vpGRGICLDLAILDSAFLLSQVAPSLFMGSI--VQLSQSVTAYMVSAAGLGLVAIYF 215
Cdd:cd17313 367 --GRGQGTDTGLLNLAISLAQILVSLLAGPIidVKGYGTVFPVAAVASFLSLVGALF 421

Solute carrier family 45 and similar sugar transporters of the Major Facilitator Superfamily of transporters; This group includes the solute carrier 45 (SLC45) family as well as plant sucrose transporters (SUCs or SUTs) and similar proteins such as Schizosaccharomyces pombe general alpha-glucoside permease. the SLC45 family is composed of four (A1-A4) vertebrate proteins as well as related insect proteins such as Drosophila sucrose transporter SCRT or Slc45-1. Members of this group transport sucrose and other sugars like maltose into the cell, with the concomitant uptake of protons (symport system). Plant sucrose transporters are crucial to carbon partitioning, playing a key role in phloem loading/unloading. They play a key role in loading and unloading of sucrose into the phloem and as a result, they control sucrose distribution throughout the whole plant and drive the osmotic flow system in the phloem. They also play a role in the exchange of sucrose between beneficial symbionts (mycorrhiza and Rhizobium) as well as pathogens such as nematodes and parasitic fungi. There are nine sucrose transporter genes in Arabidopsis and five in rice. Vertebrate SLC45 family proteins have been implicated in the regulation of glucose homoeostasis in the brain (SLC45A1), with skin and hair pigmentation (SLC45A2), and with prostate cancer and myelination (SLC45A3). Mutations in SLC45A2, also called MATP (membrane-associated transporter protein) or melanoma antigen AIM1, cause oculocutaneous albinism type 4 (OCA4), an autosomal recessive disorder of melanin biosynthesis that results in congenital hypopigmentation of ocular and cutaneous tissues. The SLC45 family and related sugar 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 52545721   1 MGSLGLFLQCAISLVFSLVMDRLVQRFGTRAVYLASVAAFPVAAGATCLSHSVAVVTASAALTGFTFSALQILPYTLASL 80
Cdd:cd17313 282 MGAWGLLIFSLAFLIFSLPIGKLGKKIGRKKVYLIGLVLFAVGMALMALVHNVTVALVLFALGGIGWATININPYPLVSD 361

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 52545721  81 YHREKqvflpkyrgdtggassedslmtsflpgpkpgapfpnghvgaggsgllppppalcgasacdvsvrvvvgeptearv 160
Cdd:cd17313 362 YHSES--------------------------------------------------------------------------- 366

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 52545721 161 vpGRGICLDLAILDSAFLLSQVAPSLFMGSI--VQLSQSVTAYMVSAAGLGLVAIYF 215
Cdd:cd17313 367 --GRGQGTDTGLLNLAISLAQILVSLLAGPIidVKGYGTVFPVAAVASFLSLVGALF 421