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 1896069471   2 GGNVFIIFVILLALFVLFVYYKVPETKNKTMEEISSMF 39
Cdd:pfam00083 415 LGYTFFIFAGLLVLFIIFVFFFVPETKGRTLEEIDELF 452

Sugar (and other) transporter;

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                  ....*....|....*....|....*....|....*...
gi 1896069471   2 GGNVFIIFVILLALFVLFVYYKVPETKNKTMEEISSMF 39
Cdd:pfam00083 415 LGYTFFIFAGLLVLFIIFVFFFVPETKGRTLEEIDELF 452

MFS transporter, sugar porter (SP) family; This model represent the sugar porter subfamily of the major facilitator superfamily (pfam00083) [Transport and binding proteins, Carbohydrates, organic alcohols, and acids]

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                  ....*....|....*....|....*....|....*
gi 1896069471   1 MGGNVFIIFVILLALFVLFVYYKVPETKNKTMEEI 35
Cdd:TIGR00879 447 GVGGVFIFFGGLNVLGLIFVYFFLPETKGRTLEEI 481

Sugar (and other) transporter;

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                  ....*....|....*....|....*....|....*...
gi 1896069471   2 GGNVFIIFVILLALFVLFVYYKVPETKNKTMEEISSMF 39
Cdd:pfam00083 415 LGYTFFIFAGLLVLFIIFVFFFVPETKGRTLEEIDELF 452

Class 1 and Class 2 Glucose transporters (GLUTs) of the Major Facilitator Superfamily; This subfamily includes Class 1 and Class 2 glucose transporters (GLUTs) including Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1, also called glucose transporter type 1 or GLUT1), SLC2A2-5 (GLUT2-5), SLC2A7 (GLUT7), SLC2A9 (GLUT9), SLC2A11 (GLUT11), SLC2A14 (GLUT14), and similar proteins. GLUTs 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). GLUTs 1-5 are the most thoroughly studied and are well-established as glucose and/or fructose transporters in various tissues and cell types. 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.

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                  ....*....|....*....|....*....|
gi 1896069471   1 MGGNVFIIFVILLALFVLFVYYKVPETKNK 30
Cdd:cd17357   418 GGGFVFIIFAIPCALFLLYLYRYLPETKGR 447

Class 2 Glucose transporters (GLUTs) of the Major Facilitator Superfamily; 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). GLUT5, also called Solute carrier family 2, facilitated glucose transporter member 5 (SLC2A5), is a well-established fructose transporter found in the small intestine. GLUT7 (or SLC2A7) is a high-affinity glucose and fructose transporter expressed in the small intestine and colon. GLUT9 (or SLC2A9) transports urate and fructose, and is most strongly expressed in the basolateral membranes of proximal renal tubular cells, liver and placenta. It may play a role in urate reabsorption by proximal tubules. GLUT11 (or SLC2A11) is a facilitative glucose transporter expressed in heart and skeletal muscle. 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.

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gi 1896069471   6 FIIFVILLALFVLFVYYKVPETKNKTMEEI 35
Cdd:cd17432   423 FLVFAVICLLTAIYIFFVLPETKGKTFLEI 452

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.

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gi 1896069471   1 MGGNVFIIFVILLALFVLFVYYKVPETKNKTMEEISSMF 39
Cdd:cd17356   365 IGFKYYYIFAGCNLLAFIVVFFFVPETKGLTLEEIDELF 403

Glucose transporter (GLUT) types 6 and 8, Class 3 GLUTs, and similar transporters of the Major Facilitator Superfamily; This subfamily is composed of glucose transporter type 6 (GLUT6), GLUT8, plant early dehydration-induced gene ERD6-like proteins, and similar insect proteins including facilitated trehalose transporter Tret1-1. 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). Insect Tret1-1 is a low-capacity facilitative transporter for trehalose that mediates the transport of trehalose synthesized in the fat body and the incorporation of trehalose into other tissues that require a carbon source. 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.

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gi 1896069471   3 GNVFIIFVILLALFVLFVYYKVPETKNKTMEE 34
Cdd:cd17358   405 SGTFWIFAGICGLALVFVLLFVPETKGKSLEE 436