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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 585679042  51 VGYGIAQTSSVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTILR 125
Cdd:cd17352  104 LGLGLIYSPAIVIVGQYFEKKRGLATGIAVAGSGVGTFVFPPLLRYLLDNYGWRGALLILGGLCLNLCVCGLLLR 178

Monocarboxylate transporter (MCT) family of the Major Facilitator Superfamily of transporters; The animal Monocarboxylate transporter (MCT) family is also called Solute carrier family 16 (SLC16 or SLC16A). It is composed of 14 members, MCT1-14. MCTs play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. MCT1-4 are proton-coupled transporters that facilitate the transport across the plasma membrane of monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and ketone bodies such as acetoacetate, beta-hydroxybutyrate and acetate. MCT8 and MCT10 are transporters which stimulate the cellular uptake of thyroid hormones such as thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine (T2). MCT10 also functions as a sodium-independent transporter that mediates the uptake or efflux of aromatic acids. Many members are orphan transporters whose substrates are yet to be determined. The MCT 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 585679042  51 VGYGIAQTSSVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTILR 125
Cdd:cd17352  104 LGLGLIYSPAIVIVGQYFEKKRGLATGIAVAGSGVGTFVFPPLLRYLLDNYGWRGALLILGGLCLNLCVCGLLLR 178

Sugar phosphate permease [Carbohydrate transport and metabolism];

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 585679042  51 VGYGIAQTSSVIGLSHYF-EKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTIL 124
Cdd:COG2271  110 LGEAGFFPAALKLIAEWFpPKERGRALGIFNAGGPLGGALAPPLLGWLLAAFGWRAAFLILGLPGLLLALLRFWL 184

Monocarboxylate transporter (MCT) family of the Major Facilitator Superfamily of transporters; The animal Monocarboxylate transporter (MCT) family is also called Solute carrier family 16 (SLC16 or SLC16A). It is composed of 14 members, MCT1-14. MCTs play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. MCT1-4 are proton-coupled transporters that facilitate the transport across the plasma membrane of monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and ketone bodies such as acetoacetate, beta-hydroxybutyrate and acetate. MCT8 and MCT10 are transporters which stimulate the cellular uptake of thyroid hormones such as thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine (T2). MCT10 also functions as a sodium-independent transporter that mediates the uptake or efflux of aromatic acids. Many members are orphan transporters whose substrates are yet to be determined. The MCT 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 585679042  51 VGYGIAQTSSVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTILR 125
Cdd:cd17352  104 LGLGLIYSPAIVIVGQYFEKKRGLATGIAVAGSGVGTFVFPPLLRYLLDNYGWRGALLILGGLCLNLCVCGLLLR 178

Monocarboxylate transporters 9 and 14, and similar proteins of the Major Facilitator Superfamily of transporters; Monocarboxylate transporters 3 (MCT3) and 4 (MCT4) are also called Solute carrier family 16 members 8 (SLC16A8) and 3 (SLC16A3), respectively. They are proton-coupled transporters that facilitate the transport across the plasma membrane of monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and ketone bodies such as acetoacetate, beta-hydroxybutyrate and acetate. MCT3 is preferentially expressed in the basolateral membrane of the retinal pigment epithelium and plays a role in pH and ion homeostasis of the outer retina by facilitating the transport of lactate and H(+) out of the retina. Mice deficient with MCT3 display altered visual function. MCT4 is highly expressed in tissues dependent on glycolysis, and it plays an important role in lactate efflux from cells. MCT4 is expressed in neurons and astrocytes; it has been found to play a role in neuroprotective mechanism of ischemic preconditioning in animals (in the gerbil) with transient cerebral ischemia. Increased MCT4 expression has also been correlated with worse prognosis across many cancer types. MCT3/4 belongs to the Monocarboxylate transporter (MCT) 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 585679042  60 SVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTILRPLQLS 130
Cdd:cd17430  113 SLIMLGRYFDKRRPLANGLAAAGSPVFLSALSPLGQILLEEYGWRGGFLILGGLLLNCCTCGAVMRPLDFS 183

Monocarboxylate transporter 12 of the of the Major Facilitator Superfamily of transporters; Monocarboxylate transporter 12 (MCT12) is also called Solute carrier family 16 member 12 (SLC16A12). It is a creatine transporter encoded by the cataract and glucosuria associated gene SLC16A12. A heterozygous mutation of the gene causes a syndrome with juvenile cataracts, microcornea, and glucosuria. MCT12 may function in a basolateral exit pathway for creatine in the proximal tubule. It belongs to the Monocarboxylate transporter (MCT) 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 585679042  51 VGYGIAQTSSVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTILRPL 127
Cdd:cd17424  104 LGFALCYSPAIAMVGKYFHKRKALAYGIAMSGSGIGTFILAPVVQLLIEQFSWRGALLILGGFVLNLCVCGALMRFL 180

Monocarboxylate transporter 14 of the Major Facilitator Superfamily of transporters; Monocarboxylate transporter 14 (MCT14) is also called Solute carrier family 16 member 14 (SLC16A14). It is an orphan transporter expressed in the brain, heart, muscle, ovary, prostate, breast, lung, pancreas, liver, spleen, and thymus. It may function as a neuronal aromatic-amino-acid transporter. MCT14 belongs to the Monocarboxylate transporter (MCT) 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 585679042  44 SFRSGSKVGYGIAQTSSVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTI 123
Cdd:cd17429   97 SFGVTAGIGSGMAYLPAVVMVGQYFQKRRALAQGLSTTGTGFGTFLMTILLKYLCAEFGWRNAMFIQGAVSLNLCVCGAL 176

                 ..
gi 585679042 124 LR 125
Cdd:cd17429  177 MR 178

Monocarboxylate transporters 8 and 10, and similar proteins of the Major Facilitator Superfamily of transporters; Monocarboxylate transporters 8 (MCT8) and 10 (MCT10) are transporters which stimulate the cellular uptake of thyroid hormones such as thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine (T2). MCT has a preference for T3 and is also a sodium-independent transporter that mediates the uptake or efflux of aromatic acids such as Phe, Tyr, and Trp, as well as L-3,4-di-hydroxy-phenylalanine. MCT8/10 and similar proteins belong to the Monocarboxylate transporter (MCT) 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 585679042  30 FYGFLLQQF--SCGTRSFRSGSKVGYG--IAQTSSVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRS 105
Cdd:cd17420   84 FGGLLLSSFcsSIGALYFTYGIMFGCGcsFAYQPSLVILGHYFKRRLGLVNGFVTAGSSVFTVILPPLLRKLLDSYGLEG 163

                         90       100       110
                 ....*....|....*....|....*....|
gi 585679042 106 ALFIVAGVNAHICLFGTILRPLQLSTENVE 135
Cdd:cd17420  164 TLRVLSLFMFVLILCSFTYRPLHPSPEDPK 193

Monocarboxylate transporter 2 of the Major Facilitator Superfamily of transporters; Monocarboxylate transporter 2 (MCT2) is also called Solute carrier family 16 member 7 (SLC16A7). It is a proton-coupled transporter that facilitates the transport across the plasma membrane of monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and ketone bodies such as acetoacetate, beta-hydroxybutyrate and acetate. It transports pyruvate and lactate outside and inside of sperm and plays roles in the regulation of spermatogenesis. Genetic variation in MCT2 has functional and clinical relevance with male infertility. MCT2 is consistently overexpressed in prostate cancer (PCa) cells and its location at peroxisomes is associated with malignant transformation. MCT2 belongs to the Monocarboxylate transporter (MCT) 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 585679042  67 YFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTILRPL 127
Cdd:cd17427  120 YFYKKRPIANGLAMAGSPVFLSTLAPLNQFLFNQFGWRGSFLILGGLLLNCCVAGSLMRPL 180

Monocarboxylate transporter 5 of the Major Facilitator Superfamily of transporters; Monocarboxylate transporter 5 (MCT5) is also called Solute carrier family 16 member 4 (SLC16A4). It is an orphan transporter expressed in the brain, muscle, liver, kidney, lung, ovary, placenta, and heart. It is a member of the monocarboxylate transporter (MCT) family, whose members include MCT1-4, which are proton-coupled transporters that facilitate the transport across the plasma membrane of monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and ketone bodies such as acetoacetate, beta-hydroxybutyrate and acetate. MCT5 belongs to the Monocarboxylate transporter (MCT) 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 585679042  48 GSKVGYGIA---QTSSVIgLSHYFEKRYATANGIMFSGAAVGMLcIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTIL 124
Cdd:cd17421   99 GLLVGLGFAflyQAAAVM-TAKYFKKRLATAYAIARSGMGLTFA-LAPFTQLLLDEYDWQGALLIFGGIMLNLVASGMLL 176

                 ....*.
gi 585679042 125 RPLQLS 130
Cdd:cd17421  177 RPIDFS 182

Monocarboxylate transporter 9 of the Major Facilitator Superfamily of transporters; Monocarboxylate transporter 9 (MCT9) is also called Solute carrier family 16 member 9 (SLC16A9). It is an orphan transporter that is expressed in a number of tissues including intestine and kidney. A missense variant of MCT9 (K258T) is associated with significant increase in susceptibility to renal overload (ROL) gout with intestinal urate underexcretion. This suggests that MCT9 may have a role in intestinal urate excretion; it is possible that it transports urate. MCT9 belongs to the Monocarboxylate transporter (MCT) 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 585679042  51 VGYGIAQTSSVIGLSHYFEKRYATANGIMFSGAAVGMLCIPPLHQIVITIYGWRSALFIVAGVNAHICLFGTILRPLQ 128
Cdd:cd17428  104 LGCGLVYAATVTITCQYFDKRRGLALGLISTGSSVGLFIYAALQRELIELYGLDGCLLIVGALALNLLACGSLMRLFK 181