major facilitator superfamily (MFS) transporter facilitates the transport across cytoplasmic or internal membranes of one or more from a variety of substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides
Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse ...
12-418
1.43e-109
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.
The actual alignment was detected with superfamily member cd17369:
Pssm-ID: 475125 [Multi-domain] Cd Length: 408 Bit Score: 328.72 E-value: 1.43e-109
Shikimate transporter and similar proteins of the Major Facilitator Superfamily; This ...
12-418
1.43e-109
Shikimate transporter and similar proteins of the Major Facilitator Superfamily; This subfamily is composed of Escherichia coli shikimate transporter (ShiA), inner membrane metabolite transport protein YhjE, and other putative metabolite transporters. ShiA is involved in the uptake of shikimate, an aromatic compound involved in siderophore biosynthesis. It has been suggested that YhjE may mediate the uptake of osmoprotectants. The ShiA-like subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340927 [Multi-domain] Cd Length: 408 Bit Score: 328.72 E-value: 1.43e-109
metabolite-proton symporter; This model represents the metabolite:H+ symport subfamily of the ...
21-412
8.94e-104
metabolite-proton symporter; This model represents the metabolite:H+ symport subfamily of the major facilitator superfamily (pfam00083), including citrate-H+ symporters, dicarboxylate:H+ symporters, the proline/glycine-betaine transporter ProP, etc. [Transport and binding proteins, Unknown substrate]
Pssm-ID: 273320 [Multi-domain] Cd Length: 394 Bit Score: 313.44 E-value: 8.94e-104
Shikimate transporter and similar proteins of the Major Facilitator Superfamily; This ...
12-418
1.43e-109
Shikimate transporter and similar proteins of the Major Facilitator Superfamily; This subfamily is composed of Escherichia coli shikimate transporter (ShiA), inner membrane metabolite transport protein YhjE, and other putative metabolite transporters. ShiA is involved in the uptake of shikimate, an aromatic compound involved in siderophore biosynthesis. It has been suggested that YhjE may mediate the uptake of osmoprotectants. The ShiA-like subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340927 [Multi-domain] Cd Length: 408 Bit Score: 328.72 E-value: 1.43e-109
metabolite-proton symporter; This model represents the metabolite:H+ symport subfamily of the ...
21-412
8.94e-104
metabolite-proton symporter; This model represents the metabolite:H+ symport subfamily of the major facilitator superfamily (pfam00083), including citrate-H+ symporters, dicarboxylate:H+ symporters, the proline/glycine-betaine transporter ProP, etc. [Transport and binding proteins, Unknown substrate]
Pssm-ID: 273320 [Multi-domain] Cd Length: 394 Bit Score: 313.44 E-value: 8.94e-104
Proline/betaine transporter of the Major Facilitator Superfamily of transporters; This ...
16-422
1.28e-87
Proline/betaine transporter of the Major Facilitator Superfamily of transporters; This subfamily is composed of Escherichia coli proline/betaine transporter, also called proline porter II (PPII), and similar proteins. ProP is a proton symporter that senses osmotic shifts and responds by importing osmolytes such as proline, glycine betaine, stachydrine, pipecolic acid, ectoine and taurine. It is both an osmosensor and an osmoregulator which is available to participate early in the bacterial osmoregulatory response. The ProP subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340924 [Multi-domain] Cd Length: 377 Bit Score: 271.54 E-value: 1.28e-87
Alpha-ketoglutarate permease of the Major Facilitator Superfamily of transporters; This ...
15-423
1.15e-85
Alpha-ketoglutarate permease of the Major Facilitator Superfamily of transporters; This subfamily includes Escherichia coli alpha-ketoglutarate permease (KgtP) and similar proteins. KgtP is a constitutively expressed proton symporter that functions in the uptake of alpha-ketoglutarate across the boundary membrane. Also included is a putative transporter from Pseudomonas aeruginosa named dicarboxylic acid transporter PcaT. The KgtP subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340925 [Multi-domain] Cd Length: 407 Bit Score: 267.24 E-value: 1.15e-85
Citrate-proton symporter of the Major Facilitator Superfamily of transporters; Citrate-proton ...
17-420
1.34e-79
Citrate-proton symporter of the Major Facilitator Superfamily of transporters; Citrate-proton symporter, also called citrate carrier protein or citrate transporter or citrate utilization protein A (CitA), is a proton symporter that functions in the uptake of citrate across the boundary membrane. It allows the utilization of citrate as a sole source of carbon and energy. In Klebsiella pneumoniae, the gene encoding this protein is called citH, instead of citA, which is the case for Escherichia coli and other organisms. CitA belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340926 [Multi-domain] Cd Length: 407 Bit Score: 251.52 E-value: 1.34e-79
Metazoan Synaptic vesicle glycoprotein 2 (SV2) and related small molecule transporters of the ...
15-417
6.36e-61
Metazoan Synaptic vesicle glycoprotein 2 (SV2) and related small molecule transporters of the Major Facilitator Superfamily; This family is composed of metazoan synaptic vesicle glycoprotein 2 (SV2) and related small molecule transporters including those that transport inorganic phosphate (Pht), aromatic compounds (PcaK and related proteins), proline/betaine (ProP), alpha-ketoglutarate (KgtP), citrate (CitA), shikimate (ShiA), and cis,cis-muconate (MucK), among others. SV2 is a transporter-like protein that serves as the receptor for botulinum neurotoxin A (BoNT/A), one of seven neurotoxins produced by the bacterium Clostridium botulinum. BoNT/A blocks neurotransmitter release by cleaving synaptosome-associated protein of 25 kD (SNAP-25) within presynaptic nerve terminals. Also included in this family is synaptic vesicle 2 (SV2)-related protein (SVOP) and similar proteins. SVOP is a transporter-like nucleotide binding protein that localizes to neurotransmitter-containing vesicles. The SV2-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.
Pssm-ID: 340874 [Multi-domain] Cd Length: 353 Bit Score: 201.68 E-value: 6.36e-61
MFS family permease, includes anhydromuropeptide permease AmpG [Carbohydrate transport and ...
2-297
8.98e-25
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];
Pssm-ID: 440245 [Multi-domain] Cd Length: 295 Bit Score: 103.35 E-value: 8.98e-25
Cis,cis-muconate transport protein and similar proteins of the Major Facilitator Superfamily; ...
27-417
1.57e-22
Cis,cis-muconate transport protein and similar proteins of the Major Facilitator Superfamily; This subfamily is composed of Acinetobacter sp. Cis,cis-muconate transport protein (MucK), Escherichia coli putative sialic acid transporter 1, and similar proteins. MucK functions in the uptake of muconate and allows Acinetobacter calcoaceticus ADP1 (BD413) to grow on exogenous cis,cis-muconate as the sole carbon source. The MucK subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340929 [Multi-domain] Cd Length: 389 Bit Score: 98.53 E-value: 1.57e-22
bacterial MdtG-like and eukaryotic solute carrier 18 (SLC18) family of the Major Facilitator ...
62-420
1.63e-15
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.
Pssm-ID: 340883 [Multi-domain] Cd Length: 375 Bit Score: 77.62 E-value: 1.63e-15
phosphate:H+ symporter; This model represents the phosphate uptake symporter subfamily of the ...
11-215
9.32e-11
phosphate:H+ symporter; This model represents the phosphate uptake symporter subfamily of the major facilitator superfamily (pfam00083). [Transport and binding proteins, Anions]
Pssm-ID: 129965 [Multi-domain] Cd Length: 502 Bit Score: 63.59 E-value: 9.32e-11
Methylenomycin A resistance protein (also called MMR peptide) and similar multidrug resistance ...
74-307
8.12e-10
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.
Pssm-ID: 340879 [Multi-domain] Cd Length: 370 Bit Score: 60.26 E-value: 8.12e-10
Purine ribonucleoside efflux pump NepI and similar transporters of the Major Facilitator ...
50-307
1.61e-09
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.
Pssm-ID: 340882 [Multi-domain] Cd Length: 370 Bit Score: 59.10 E-value: 1.61e-09
Major Facilitator Superfamily; The Major Facilitator Superfamily (MFS) is a large and diverse ...
62-416
9.11e-09
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.
Pssm-ID: 349949 [Multi-domain] Cd Length: 378 Bit Score: 57.05 E-value: 9.11e-09
4-hydroxybenzoate transporter PcaK and similar transporters of the Major Facilitator ...
22-197
1.47e-08
4-hydroxybenzoate transporter PcaK and similar transporters of the Major Facilitator Superfamily; This aromatic acid:H(+) symporter subfamily includes Acinetobacter sp. 4-hydroxybenzoate transporter PcaK, Pseudomonas putida gallate transporter (GalT), Corynebacterium glutamicum gentisate transporter (GenK), Nocardioides sp. 1-hydroxy-2-naphthoate transporter (PhdT), Escherichia coli 3-(3-hydroxy-phenyl)propionate (3HPP) transporter (MhpT), and similar proteins. These transporters are involved in the uptake across the cytoplasmic membrane of specific aromatic compounds such as 4-hydroxybenzoate, gallate, gentisate (2,5-dihydroxybenzoate), 1-hydroxy-2-naphthoate, and 3HPP, respectively. The PcaK-like aromatic acid:H(+) symporter subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340923 [Multi-domain] Cd Length: 351 Bit Score: 56.05 E-value: 1.47e-08
Inorganic Phosphate Transporter of the Major Facilitator Superfamily of transporters; This ...
15-208
1.66e-08
Inorganic Phosphate Transporter of the Major Facilitator Superfamily of transporters; This subfamily is composed of predominantly fungal and plant high-affinity inorganic phosphate transporters (PhT or PiPT), which are involved in the uptake, translocation, and internal transport of inorganic phosphate. They also function in sensing external phosphate levels as transceptors. Phosphate is crucial for structural and metabolic needs, including nucleotide and lipid synthesis, signalling and chemical energy storage. The Pht subfamily belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) 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.
Pssm-ID: 340922 [Multi-domain] Cd Length: 389 Bit Score: 56.13 E-value: 1.66e-08
Hexuronate transporter, Glucarate transporter, and similar transporters of the Major ...
54-419
1.84e-08
Hexuronate transporter, Glucarate transporter, and similar transporters of the Major Facilitator Superfamily; This family is composed of predominantly bacterial transporters for hexuronate (ExuT), glucarate (GudP), galactarate (GarP), and galactonate (DgoT). They mediate the uptake of these compounds into the cell. They 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.
Pssm-ID: 340877 [Multi-domain] Cd Length: 358 Bit Score: 56.04 E-value: 1.84e-08
D-xylose-proton symporter and similar transporters of the Major Facilitator Superfamily; This ...
71-372
4.68e-08
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.
Pssm-ID: 340917 [Multi-domain] Cd Length: 383 Bit Score: 54.88 E-value: 4.68e-08
Fungal Hexose transporter subfamily of the Major Facilitator Superfamily of transporters and ...
53-305
3.21e-07
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.
Pssm-ID: 340914 [Multi-domain] Cd Length: 403 Bit Score: 52.25 E-value: 3.21e-07
Putative arabinose efflux permease family transporters of the Major Facilitator Superfamily; ...
52-307
4.07e-07
Putative arabinose efflux permease family transporters of the Major Facilitator Superfamily; This family includes a group of putative arabinose efflux permease family transporters, such as alpha proteobacterium quinolone resistance protein NorA (characterized Staphylococcus aureus Quinolone resistance protein NorA belongs to a different group), Desulfovibrio dechloracetivorans bacillibactin exporter, Vibrio aerogenes antiseptic resistance protein. The biological function of those transporters remain unclear. They 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.
Pssm-ID: 341026 [Multi-domain] Cd Length: 374 Bit Score: 51.81 E-value: 4.07e-07
Saccharomyces cerevisiae Azole resistance protein 1 (Azr1p), and similar multidrug resistance ...
75-302
4.19e-06
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.
Pssm-ID: 341045 [Multi-domain] Cd Length: 337 Bit Score: 48.33 E-value: 4.19e-06
Class 1 and Class 2 Glucose transporters (GLUTs) of the Major Facilitator Superfamily; This ...
63-218
6.65e-06
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.
Pssm-ID: 340915 [Multi-domain] Cd Length: 447 Bit Score: 48.03 E-value: 6.65e-06
Multidrug resistance protein MdtG and similar multidrug resistance (MDR) transporters of the ...
62-197
1.92e-05
Multidrug resistance protein MdtG and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This subfamily is composed of Escherichia coli multidrug resistance protein MdtG, Streptococcus pneumoniae multidrug resistance efflux pump PmrA, and similar multidrug resistance (MDR) transporters from bacteria. 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. MdtG confers resistance to fosfomycin and deoxycholate. PmrA serves as an efflux pump for various substrates and is associated with fluoroquinolone resistance. MdtG-like MDR 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.
Pssm-ID: 340949 [Multi-domain] Cd Length: 380 Bit Score: 46.49 E-value: 1.92e-05
Macrolide efflux protein A and similar proteins of the Major Facilitator Superfamily of ...
62-307
2.89e-05
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.
Pssm-ID: 340863 [Multi-domain] Cd Length: 383 Bit Score: 46.07 E-value: 2.89e-05
Solute carrier family 22 members 1, 2, and 3 (also called Organic cation transporters 1, 2, ...
55-176
3.08e-05
Solute carrier family 22 members 1, 2, and 3 (also called Organic cation transporters 1, 2, and 3) of the Major Facilitator Superfamily of transporters; This sufamily includes solute carrier family 22 member 1 (SLC22A1, also called organic cation transporter 1 or OCT1), SLC22A2 (or OCT2), SLC22A3 (or OCT3), and similar proteins. OCT1-3 have similar basic functional properties: they are able to translocate a variety of structurally different organic cations in both directions across the plasma membrane; to translocate organic cations independently from sodium, chloride or proton gradients; and to function as electrogenic uniporters for cations or as electroneutral cation exchangers. They show overlapping but distinct substrate and inhibitor specificities, and different tissue expression pattern. In humans, OCT1 is strongly expressed in the liver, OCT2 is highly expressed in the kidney where it is localized at the basolateral membrane of renal proximal tubules, and OCT3 is most strongly expressed in skeletal muscle. OCTs are broad-specificity transporters that play a critical role in the excretion and distribution of endogeneous organic cations and for the uptake, elimination and distribution of cationic drugs, toxins, and environmental waste products. The SLC22A1-3 subfamily belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters 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.
Pssm-ID: 340937 [Multi-domain] Cd Length: 340 Bit Score: 45.80 E-value: 3.08e-05
Methylenomycin A resistance protein (also called MMR peptide)-like multidrug resistance (MDR) ...
75-303
6.63e-05
Methylenomycin A resistance protein (also called MMR peptide)-like multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This subfamily is composed of putative multidrug resistance (MDR) transporters including Chlamydia trachomatis antiseptic resistance protein QacA_2, and Serratia sp. DD3 Bmr3. 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.
Pssm-ID: 341047 [Multi-domain] Cd Length: 371 Bit Score: 44.88 E-value: 6.63e-05
Yeast Polyamine transporter 1 (Tpo1) and similar multidrug resistance (MDR) transporters of ...
53-205
1.12e-04
Yeast Polyamine transporter 1 (Tpo1) and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This family is composed of fungal multidrug resistance (MDR) transporters including several proteins from Saccharomyces cerevisiae such as polyamine transporters 1-4 (Tpo1-4), quinidine resistance proteins 1-3 (Qdr1-3), dityrosine transporter 1 (Dtr1), fluconazole resistance protein 1 (Flr1), and protein HOL1. 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, Flr1 confers resistance to the azole derivative fluconazole while Tpo1 confers resistance and adaptation to quinidine and ketoconazole. The polyamine transporters are involved in the detoxification of excess polyamines in the cytoplasm. Tpo1-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.
Pssm-ID: 340881 [Multi-domain] Cd Length: 376 Bit Score: 44.10 E-value: 1.12e-04
Organic anion transporters of the Major Facilitator Superfamily of transporters; Organic anion ...
70-169
1.17e-04
Organic anion transporters of the Major Facilitator Superfamily of transporters; Organic anion transporters (OATs) generally display broad substrate specificity and they facilitate the exchange of extracellular with intracellular organic anions (OAs). Several OATs have been characterized including OAT1-10 and urate anion exchanger 1 (URAT1, also called SLC22A12). Many OATs occur in renal proximal tubules, the site of active drug secretion. OATs mediate the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories, and therefore is critical for the survival of the mammalian species. OAT falls into the SLC22 (solute carrier 22) family of 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.
Pssm-ID: 340932 [Multi-domain] Cd Length: 341 Bit Score: 43.82 E-value: 1.17e-04
Glucose transporter (GLUT) types 6 and 8, Class 3 GLUTs, and similar transporters of the Major ...
70-388
1.40e-04
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.
Pssm-ID: 340916 [Multi-domain] Cd Length: 436 Bit Score: 44.10 E-value: 1.40e-04
Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major ...
71-177
1.65e-04
Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters of the Major Facilitator Superfamily; The Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters includes organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). SLC22 transporters interact with a variety of compounds that include drugs of abuse, environmental toxins, opioid analgesics, antidepressant and anxiolytic agents, and neurotransmitters and their metabolites. The SLC22 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.
Pssm-ID: 340875 [Multi-domain] Cd Length: 331 Bit Score: 43.34 E-value: 1.65e-04
YcaD and similar transporters of the Major Facilitator Superfamily; This family is composed of ...
32-307
1.72e-04
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.
Pssm-ID: 341030 [Multi-domain] Cd Length: 360 Bit Score: 43.32 E-value: 1.72e-04
Fosmidomycin resistance protein of the Major Facilitator Superfamily of transporters; ...
56-307
2.11e-04
Fosmidomycin resistance protein of the Major Facilitator Superfamily of transporters; Fosmidomycin resistance protein (FsR) confers resistance against fosmidomycin. It shows sequence similarity with the bacterial drug-export proteins that mediate resistance to tetracycline and chloramphenicol. This FsR 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.
Pssm-ID: 341031 [Multi-domain] Cd Length: 365 Bit Score: 43.31 E-value: 2.11e-04
Bacillus subtilis multidrug efflux protein YfmO and similar transporters of the Major ...
54-307
2.45e-04
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.
Pssm-ID: 341027 [Multi-domain] Cd Length: 374 Bit Score: 42.94 E-value: 2.45e-04
MJ1317 and similar transporters of the Major Facilitator Superfamily; This family is composed ...
62-189
3.79e-04
MJ1317 and similar transporters of the Major Facilitator Superfamily; This family is composed of Methanocaldococcus jannaschii MFS-type transporter MJ1317, Mycobacterium bovis protein Mb2288, 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.
Pssm-ID: 340928 [Multi-domain] Cd Length: 371 Bit Score: 42.53 E-value: 3.79e-04
Escherichia coli YfcJ, YhhS, and similar transporters of the Major Facilitator Superfamily; ...
29-307
7.87e-04
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.
Pssm-ID: 341042 [Multi-domain] Cd Length: 367 Bit Score: 41.43 E-value: 7.87e-04
Glucose transporters (GLUTs) and other similar sugar transporters of the Major Facilitator ...
17-372
7.88e-04
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.
Pssm-ID: 340873 [Multi-domain] Cd Length: 365 Bit Score: 41.41 E-value: 7.88e-04
MJ1317 and similar transporters of the Major Facilitator Superfamily; This family is composed ...
168-417
1.51e-03
MJ1317 and similar transporters of the Major Facilitator Superfamily; This family is composed of Methanocaldococcus jannaschii MFS-type transporter MJ1317, Mycobacterium bovis protein Mb2288, 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.
Pssm-ID: 340928 [Multi-domain] Cd Length: 371 Bit Score: 40.60 E-value: 1.51e-03
Plant Sugar transport protein subfamily of the Major Facilitator Superfamily of transporters; ...
72-305
2.09e-03
Plant Sugar transport protein subfamily of the Major Facilitator Superfamily of transporters; The plant Sugar transport protein (STP) subfamily includes STP1-STP14; they are also called hexose transporters. They mediate the active uptake of hexoses such as glucose, 3-O-methylglucose, fructose, xylose, mannose, galactose, fucose, 2-deoxyglucose and arabinose, by sugar/hydrogen symport. Several STP family transporters are expressed in a tissue-specific manner, or at specific developmental stages. STP1 is the member with the highest expression level of all members and high expression is detected in photosynthetic tissues, such as leaves and stems, while roots, siliques, and flowers show lower expression levels. It plays a major role in the uptake and response of Arabidopsis seeds and seedlings to sugars. The STP 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.
Pssm-ID: 340919 [Multi-domain] Cd Length: 390 Bit Score: 40.31 E-value: 2.09e-03
Solute carrier family 22 member 6 (also called Organic anion transporter 1) and similar ...
71-176
2.76e-03
Solute carrier family 22 member 6 (also called Organic anion transporter 1) and similar transporters of the Major Facilitator Superfamily; This subfamily includes solute carrier family 22 member 6 (SLC22A6, also called organic anion transporter 1 or OAT1 or para-aminohippurate (PAH) transporter), SLC22A8 (or OAT3), and SLC22A20 (or OAT6). OAT1 and OAT3 are involved in the renal elimination of endogenous and exogenous organic anions (OAs). They function as OA exchangers, coupling the uptake of OAs against an electrochemical gradient with the efflux of intracellular dicarboxylates. SLC22A20 is an OA transporter that mediates the uptake of estrone sulfate. The OAT1-like subfamily belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters 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.
Pssm-ID: 341004 [Multi-domain] Cd Length: 339 Bit Score: 39.71 E-value: 2.76e-03
Bacillus subtilis lincomycin resistance protein (LmrB) and similar multidrug resistance (MDR) ...
79-307
2.79e-03
Bacillus subtilis lincomycin resistance protein (LmrB) and similar multidrug resistance (MDR) transporters of the Major Facilitator Superfamily; This subfamily is composed of multidrug resistance (MDR) transporters including Bacillus subtilis lincomycin resistance protein LmrB, and several proteins from Escherichia coli such as the putative MDR transporters EmrB, MdtD, and YieQ. 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. 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.
Pssm-ID: 341046 [Multi-domain] Cd Length: 380 Bit Score: 39.87 E-value: 2.79e-03
Plant organic cation/carnitine transporters of the Major Facilitator Superfamily of ...
71-188
5.26e-03
Plant organic cation/carnitine transporters of the Major Facilitator Superfamily of transporters; Plant organic cation/carnitine transporters (OCTs) are sequence-similar to their animal counterparts, which are broad-specificity transporters that play a critical role in the excretion and distribution of endogeneous organic cations and for the uptake, elimination and distribution of cationic drugs, toxins, and environmental waste products. Little is know about plant OCTs. In Arabidopsis, there are six genes belonging to this family that show distinct, organ-specific expression pattern of the individual genes. AtOCT1 has been found to affect root development and carnitine-related responses in Arabidopsis. AtOCT4, 5 and 6 are up-regulated during drought stress, AtOCT3 and 5 during cold stress and AtOCT5 and 6 during salt stress treatments. Plant OCTs belongs to the Solute carrier 22 (SLC22) family of organic cation/anion/zwitterion transporters 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.
Pssm-ID: 340936 [Multi-domain] Cd Length: 342 Bit Score: 38.88 E-value: 5.26e-03
Protein spinster and spinster homologs of the Major Facilitator Superfamily of transporters; ...
73-304
6.09e-03
Protein spinster and spinster homologs of the Major Facilitator Superfamily of transporters; The protein spinster family includes Drosophila protein spinster, its vertebrate homologs, and similar proteins. Humans contain three homologs called protein spinster homologs 1 (SPNS1), 2 (SPNS2), and 3 (SPNS3). Protein spinster and its homologs may be sphingolipid transporters that play central roles in endosomes and/or lysosomes storage. SPNS2 is also called sphingosine 1-phosphate (S1P) transporter and is required for migration of myocardial precursors. S1P is a secreted lipid mediator that plays critical roles in cardiovascular, immunological, and neural development and function. The spinster-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.
Pssm-ID: 340886 [Multi-domain] Cd Length: 405 Bit Score: 38.76 E-value: 6.09e-03
Multidrug transporter MdfA and similar multidrug resistance (MDR) transporters of the Major ...
71-418
6.51e-03
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.
Pssm-ID: 340878 [Multi-domain] Cd Length: 379 Bit Score: 38.71 E-value: 6.51e-03
Fungal trichothecene efflux pump (TRI12) of the Major Facilitator Superfamily of transporters; ...
274-416
9.62e-03
Fungal trichothecene efflux pump (TRI12) of the Major Facilitator Superfamily of transporters; This family includes Fusarium sporotrichioides trichothecene efflux pump (TRI12), which may play a role in F. sporotrichioides self-protection against trichothecenes. TRI12 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.
Pssm-ID: 340868 [Multi-domain] Cd Length: 518 Bit Score: 38.38 E-value: 9.62e-03
Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01
References:
Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
of the residues that compose this conserved feature have been mapped to the query sequence.
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