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

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gi 26340248 127 EFLEEeNVRIGILFASKALMQLLVNPFVGPLTNRIGYHIPMFVGFMIMFLSTLskSFAF 185
Cdd:cd17384  25 DYLNE-NVRVGLLFASKALVQLITNPIVGPLTNRIGYSLPMFVGFVIMFISTL--LFAF 80

Vesicular amine transporters 1 (VAT1) and 2 (VAT2), and similar transporters of the Major Facilitator Superfamily; Vesicular amine transporter 1 (VAT1 or VMAT1) is also called solute carrier family 18 member 1 (SLC18A1) or chromaffin granule amine transporter, while VAT2 (or VMAT2) is also called SLC18A2, synaptic vesicular amine transporter, or monoamine transporter. VATs (or VMATs) are responsible for the uptake of cytosolic monoamines into synaptic vesicles in monoaminergic neurons. VAT1 and VAT2 distinct pharmacological properties and tissue distributions. VAT1 is preferentially expressed in neuroendocrine cells and endocrine cells, where it transports biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles. VAT2 is primarily expressed in the CNS and is involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. VATs 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....
gi 26340248 127 EFLEEeNVRIGILFASKALMQLLVNPFVGPLTNRIGYHIPMFVGFMIMFLSTLskSFAF 185
Cdd:cd17384  25 DYLNE-NVRVGLLFASKALVQLITNPIVGPLTNRIGYSLPMFVGFVIMFISTL--LFAF 80

Vesicular amine transporters 1 (VAT1) and 2 (VAT2), and similar transporters of the Major Facilitator Superfamily; Vesicular amine transporter 1 (VAT1 or VMAT1) is also called solute carrier family 18 member 1 (SLC18A1) or chromaffin granule amine transporter, while VAT2 (or VMAT2) is also called SLC18A2, synaptic vesicular amine transporter, or monoamine transporter. VATs (or VMATs) are responsible for the uptake of cytosolic monoamines into synaptic vesicles in monoaminergic neurons. VAT1 and VAT2 distinct pharmacological properties and tissue distributions. VAT1 is preferentially expressed in neuroendocrine cells and endocrine cells, where it transports biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles. VAT2 is primarily expressed in the CNS and is involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. VATs 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....
gi 26340248 127 EFLEEeNVRIGILFASKALMQLLVNPFVGPLTNRIGYHIPMFVGFMIMFLSTLskSFAF 185
Cdd:cd17384  25 DYLNE-NVRVGLLFASKALVQLITNPIVGPLTNRIGYSLPMFVGFVIMFISTL--LFAF 80

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.

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gi 26340248 133 NVRIGILFASKALMQLLVNPFVGPLTNRIGYHIPMFVGFMIMFLSTL 179
Cdd:cd17325  30 VAQIGLIVAAYALAQLLFSPPAGRLSDRFGRKRLLLLGLLLLAVSTL 76