Major facilitator superfamily

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Major Facilitator Superfamily
2y5y.png
Crystal Structure of Lactose Permease LacY.
Identifiers
SymbolMFS
Pfam clan CL0015
ECOD 5050.1.1
TCDB 2.A.1
OPM superfamily 15
CDD cd06174

The major facilitator superfamily (MFS) is a superfamily of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients. [1] [2]

Contents

Function

The major facilitator superfamily (MFS) are membrane proteins which are expressed ubiquitously in all kingdoms of life for the import or export of target substrates. The MFS family was originally believed to function primarily in the uptake of sugars but subsequent studies revealed that drugs, metabolites, oligosaccharides, amino acids and oxyanions were all transported by MFS family members. [3] These proteins energetically drive transport utilizing the electrochemical gradient of the target substrate (uniporter), or act as a cotransporter where transport is coupled to the movement of a second substrate.

Fold

The basic fold of the MFS transporter is built around 12, [4] or in some cases, 14 transmembrane helices [5] (TMH), with two 6- (or 7- ) helix bundles formed by the N and C terminal homologous domains [6] of the transporter which are connected by an extended cytoplasmic loop. The two halves of the protein pack against each other in a clam-shell fashion, sealing via interactions at the ends of the transmembrane helices and extracellular loops. [7] [8] This forms a large aqueous cavity at the center of the membrane, which is alternatively open to the cytoplasm or periplasm/extracellular space. Lining this aqueous cavity are the amino-acids which bind the substrates and define transporter specificity. [9] [10] Many MFS transporters are thought to be dimers through in vitro and in vivo methods, with some evidence to suggest a functional role for this oligomerization. [11]

Mechanism

The alternating-access mechanism thought to underlie the transport of most MFS transport is classically described as the "rocker-switch" mechanism. [7] [8] In this model, the transporter opens to either the extracellular space or cytoplasm and simultaneously seals the opposing face of the transporter, preventing a continuous pathway across the membrane. For example, in the best studied MFS transporter, LacY, lactose and protons typically bind from the periplasm to specific sites within the aqueous cleft. This drives closure of the extracellular face, and opening of the cytoplasmic side, allowing substrate into the cell. Upon substrate release, the transporter recycles to the periplasmic facing orientation.

Structure of LacY open to the periplasm (left) or cytoplasm (right). Sugar analogs are shown bound in the cleft of both structures. LacY states.png
Structure of LacY open to the periplasm (left) or cytoplasm (right). Sugar analogs are shown bound in the cleft of both structures.

Exporters and antiporters of the MFS family follow a similar reaction cycle, though exporters bind substrate in the cytoplasm and extrude it to the extracellular or periplasmic space, while antiporters bind substrate in both states to drive each conformational change. While most MFS structures suggest large, rigid body structural changes with substrate binding, the movements may be small in the cases of small substrates, such as the nitrate transporter NarK. [12]

Transport

The generalized transport reactions catalyzed by MFS porters are:

  1. Uniport: S (out) ⇌ S (in)
  2. Symport: S (out) + [H+ or Na+] (out) ⇌ S (in) + [H+ or Na+] (in)
  3. Antiport: S1 (out) + S2 (in) ⇌ S1 (in) + S2 (out) (S1 may be H+ or a solute)

Substrate specificity

Though initially identified as sugar transporters, a function conserved from prokaryotes [10] to mammals, [13] the MFS family is notable for the great diversity of substrates transported by the superfamily. These range from small oxyanions [14] [15] [16] to large peptide fragments. [17] Other MFS transporters are notable for a lack of selectivity, extruding broad classes of drugs and xenobiotics. [18] [19] [20] This substrate specificity is largely determined by specific side chains which line the aqueous pocket at the center of the membrane. [9] [10] While one substrate of particular biological importance is often used to name the transporter or family, there may also be co-transported or leaked ions or molecules. These include water molecules [21] [22] or the coupling ions which energetically drive transport.

Structures

Crystal structure of GlpT in the inward facing state, with helical N and C domains colored purple and blue respectively. Loops colored green.

The crystal structures of a number of MFS transporters have been characterized. The first structures were of the glycerol 3-phosphate/phosphate exchanger GlpT [8] and the lactose-proton symporter LacY, [7] which served to elucidate the overall structure of the protein family and provided initial models for understanding the MFS transport mechanism. Since these initial structures other MFS structures have been solved which illustrate substrate specificity or states within the reaction cycle. [23] [24] While the initial MFS structures solved were of bacterial transporters, recently structures of the first eukaryotic structures have been published. These include a fungal phosphate transporter PiPT, [16] plant nitrate transporter NRT1.1, [11] [25] and the human glucose transporter GLUT1. [26]

Evolution

The origin of the basic MFS transporter fold is currently under heavy debate. All currently recognized MFS permeases have the two six-TMH domains within a single polypeptide chain, although in some MFS families an additional two TMHs are present. Evidence suggests that the MFS permeases arose by a tandem intragenic duplication event in the early prokaryotes. This event generated the 12 transmembrane helix topology from a (presumed) primordial 6-helix dimer. Moreover, the well-conserved MFS specific motif between TMS2 and TMS3 and the related but less well conserved motif between TMS8 and TMS9 prove to be a characteristic of virtually all of the more than 300 MFS proteins identified. [27] However, the origin of the primordial 6-helix domain is under heavy debate. While some functional and structural evidence suggests that this domain arose out of a simpler 3-helix domain, [28] [29] bioinformatic or phylogenetic evidence supporting this hypothesis is lacking. [30] [31]

Medical significance

MFS family members are central to human physiology and play an important role in a number of diseases, through aberrant action, drug transport, or drug resistance. The OAT1 transporter transports a number of nucleoside analogs central to antiviral therapy. [32] Resistance to antibiotics is frequently the result of action of MFS resistance genes. [33] Mutations in MFS transporters have also been found to cause neurodegerative disease, [34] vascular disorders of the brain, [35] and glucose storage diseases. [36]

Disease mutations

Disease associated mutations have been found in a number of human MFS transporters; those annotated in Uniprot are listed below.

Human MFS proteins

There are several MFS proteins in humans, where they are known as solute carriers (SLCs) and Atypical SLCs. [62] There are today 52 SLC families, [63] of which 16 families include MFS proteins; SLC2, 15 16, 17, 18, 19, SLCO (SLC21), 22, 29, 33, 37, 40, 43, 45, 46 and 49. [62] Atypical SLCs are MFS proteins, sharing sequence similarities and evolutionary origin with SLCs, [62] [64] [65] [66] but they are not named according to the SLC root system, which originates from the hugo gene nomenclature system (HGNC). [67] All atypical SLCs are listed in detail in, [62] but they are: MFSD1, [66] MFSD2A, [68] MFSD2B, MFSD3, [66] MFSD4A, [69] MFSD4B, [70] MFSD5, [64] MFSD6, [65] MFSD6L, MFSD8, [71] MFSD9, [65] [69] MFSD10, [65] [72] MFSD11, [64] MFSD12, MFSD13A, MFSD14A, [65] [73] MFSD14B, [65] [73] UNC93A, [74] [75] [76] UNC93B1, [77] SV2A, SV2B, SV2C, SVOP, SVOPL, SPNS1, [78] SPNS2, SPNS3 and CLN3. [79] As there is high sequence identity and phylogenetic resemblance between the atypical SLCs of MFS type, they can be divided into 15 AMTFs (Atypical MFS Transporter Families), suggesting there are at least 64 different families including SLC proteins of MFS type. [80]

Related Research Articles

<span class="mw-page-title-main">Uniporter</span>

Uniporters, also known as solute carriers or facilitated transporters, are a type of membrane transport protein that passively transports solutes across a cell membrane. It uses facilitated diffusion for the movement of solutes down their concentration gradient from an area of high concentration to an area of low concentration. Unlike active transport, it does not require energy in the form of ATP to function. Uniporters are specialized to carry one specific ion or molecule and can be categorized as either channels or carriers. Facilitated diffusion may occur through three mechanisms: uniport, symport, or antiport. The difference between each mechanism depends on the direction of transport, in which uniport is the only transport not coupled to the transport of another solute.

<span class="mw-page-title-main">GLUT2</span> Transmembrane carrier protein

Glucose transporter 2 (GLUT2) also known as solute carrier family 2, member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the principal transporter for transfer of glucose between liver and blood Unlike GLUT4, it does not rely on insulin for facilitated diffusion.

<span class="mw-page-title-main">Glucose transporter</span> Family of monosaccharide transport proteins

Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose across the plasma membrane, a process known as facilitated diffusion. Because glucose is a vital source of energy for all life, these transporters are present in all phyla. The GLUT or SLC2A family are a protein family that is found in most mammalian cells. 14 GLUTS are encoded by the human genome. GLUT is a type of uniporter transporter protein.

<span class="mw-page-title-main">Ferroportin</span> Protein

Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the SLC40A1 gene. Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell. Ferroportin is the only known iron exporter.

<span class="mw-page-title-main">Ion transporter</span> Transmembrane protein that moves ions across a biological membrane

In biology, an ion transporter is a transmembrane protein that moves ions across a biological membrane to accomplish many different biological functions, including cellular communication, maintaining homeostasis, energy production, etc. There are different types of transporters including pumps, uniporters, antiporters, and symporters. Active transporters or ion pumps are transporters that convert energy from various sources—including adenosine triphosphate (ATP), sunlight, and other redox reactions—to potential energy by pumping an ion up its concentration gradient. This potential energy could then be used by secondary transporters, including ion carriers and ion channels, to drive vital cellular processes, such as ATP synthesis.

<span class="mw-page-title-main">GLUT1</span> Uniporter protein

Glucose transporter 1, also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the SLC2A1 gene. GLUT1 facilitates the transport of glucose across the plasma membranes of mammalian cells. This gene encodes a facilitative glucose transporter that is highly expressed in erythrocytes and endothelial cells, including cells of the blood–brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. GLUT1 accounts for 2 percent of the protein in the plasma membrane of erythrocytes.

<span class="mw-page-title-main">Battenin</span> Protein found in humans

Battenin is a protein that in humans is encoded by the CLN3 gene located on chromosome 16. Battenin is not clustered into any Pfam clan, but it is included in the TCDB suggesting that it is a transporter. In humans, it belongs to the atypical SLCs due to its structural and phylogenetic similarity to other SLC transporters.

The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO Gene Nomenclature Committee (HGNC) and is the basis for the official HGNC names of the genes that encode these transporters. A more general transmembrane transporter classification can be found in TCDB database.

<span class="mw-page-title-main">Sulfate transporter</span> Protein-coding gene in the species Homo sapiens

The sulfate transporter is a solute carrier family protein that in humans is encoded by the SLC26A2 gene. SLC26A2 is also called the diastrophic dysplasia sulfate transporter (DTDST), and was first described by Hästbacka et al. in 1994. A defect in sulfate activation described by Superti-Furga in achondrogenesis type 1B was subsequently also found to be caused by genetic variants in the sulfate transporter gene. This sulfate (SO42−) transporter also accepts chloride, hydroxyl ions (OH−), and oxalate as substrates. SLC26A2 is expressed at high levels in developing and mature cartilage, as well as being expressed in lung, placenta, colon, kidney, pancreas and testis.

<span class="mw-page-title-main">Sodium/glucose cotransporter 1</span>

Sodium/glucose cotransporter 1 (SGLT1) also known as solute carrier family 5 member 1 is a protein in humans that is encoded by the SLC5A1 gene which encodes the production of the SGLT1 protein to line the absorptive cells in the small intestine and the epithelial cells of the kidney tubules of the nephron for the purpose of glucose uptake into cells. Recently, it has been seen to have functions that can be considered as promising therapeutic target to treat diabetes and obesity. Through the use of the sodium glucose cotransporter 1 protein, cells are able to obtain glucose which is further utilized to make and store energy for the cell.

<span class="mw-page-title-main">RAC1</span> Protein-coding gene in humans

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

<span class="mw-page-title-main">ABCG2</span> Protein-coding gene in the species Homo sapiens

ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ABCG2 gene. ABCG2 has also been designated as CDw338. ABCG2 is a translocation protein used to actively pump drugs and other compounds against their concentration gradient using the bonding and hydrolysis of ATP as the energy source.

<span class="mw-page-title-main">Glucose-6-phosphate exchanger SLC37A4</span>

Glucose-6-phosphate exchanger SLC37A4, also known as glucose-6-phosphate translocase, is an enzyme that in humans is encoded by the SLC37A4 gene.

<span class="mw-page-title-main">ABCA4</span> Mammalian protein found in Homo sapiens

ATP-binding cassette, sub-family A (ABC1), member 4, also known as ABCA4 or ABCR, is a protein which in humans is encoded by the ABCA4 gene.

<span class="mw-page-title-main">SLC22A4</span> Protein-coding gene in humans

Solute carrier family 22, member 4, also known as SLC22A4, is a human gene; the encoded protein is known as the ergothioneine transporter.

<span class="mw-page-title-main">SLC22A11</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 22 member 11 is a protein that in humans is encoded by the SLC22A11 gene.

<span class="mw-page-title-main">Tricarboxylate transport protein, mitochondrial</span> Mammalian protein found in Homo sapiens

Tricarboxylate transport protein, mitochondrial, also known as tricarboxylate carrier protein and citrate transport protein (CTP), is a protein that in humans is encoded by the SLC25A1 gene. SLC25A1 belongs to the mitochondrial carrier gene family SLC25. High levels of the tricarboxylate transport protein are found in the liver, pancreas and kidney. Lower or no levels are present in the brain, heart, skeletal muscle, placenta and lung.

<span class="mw-page-title-main">MFSD8</span> Protein-coding gene in the species Homo sapiens

Major facilitator superfamily domain containing 8 also called MFSD8 is a protein that in humans is encoded by the MFSD8 gene. MFSD8 is an atypical SLC, thus a predicted SLC transporter. It clusters phylogenetically to the Atypical MFS Transporter family 2 (AMTF2).

<span class="mw-page-title-main">UNC93A</span> Protein-coding gene in the species Homo sapiens

Unc-93 homolog A is a protein that in humans is encoded by the UNC93A gene.

Atypical Solute Carrier Families are novel plausible secondary active or facilitative transporter proteins that share ancestral background with the known solute carrier families (SLCs). However, they have not been assigned a name according to the SLC root system, or been classified into any of the existing SLC families.

References

  1. ↑ Pao SS, Paulsen IT, Saier MH (March 1998). "Major facilitator superfamily". Microbiology and Molecular Biology Reviews. 62 (1): 1–34. doi:10.1128/MMBR.62.1.1-34.1998. PMC   98904 . PMID   9529885.
  2. ↑ Walmsley AR, Barrett MP, Bringaud F, Gould GW (December 1998). "Sugar transporters from bacteria, parasites and mammals: structure-activity relationships". Trends in Biochemical Sciences. 23 (12): 476–81. doi:10.1016/S0968-0004(98)01326-7. PMID   9868370.
  3. ↑ Marger MD, Saier MH (January 1993). "A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport". Trends in Biochemical Sciences. 18 (1): 13–20. doi:10.1016/0968-0004(93)90081-w. PMID   8438231.
  4. ↑ Foster DL, Boublik M, Kaback HR (January 1983). "Structure of the lac carrier protein of Escherichia coli". The Journal of Biological Chemistry. 258 (1): 31–4. doi: 10.1016/S0021-9258(18)33213-7 . PMID   6336750.
  5. ↑ Paulsen IT, Brown MH, Littlejohn TG, Mitchell BA, Skurray RA (April 1996). "Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: membrane topology and identification of residues involved in substrate specificity". Proceedings of the National Academy of Sciences of the United States of America. 93 (8): 3630–5. Bibcode:1996PNAS...93.3630P. doi: 10.1073/pnas.93.8.3630 . PMC   39662 . PMID   8622987.
  6. ↑ Maiden MC, Davis EO, Baldwin SA, Moore DC, Henderson PJ (Feb 12–18, 1987). "Mammalian and bacterial sugar transport proteins are homologous". Nature. 325 (6105): 641–3. Bibcode:1987Natur.325..641M. doi:10.1038/325641a0. PMID   3543693. S2CID   4353429.
  7. 1 2 3 Abramson J, Smirnova I, Kasho V, Verner G, Kaback HR, Iwata S (August 2003). "Structure and mechanism of the lactose permease of Escherichia coli". Science. 301 (5633): 610–5. Bibcode:2003Sci...301..610A. doi:10.1126/science.1088196. PMID   12893935. S2CID   36908983.
  8. 1 2 3 Huang Y, Lemieux MJ, Song J, Auer M, Wang DN (August 2003). "Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli". Science. 301 (5633): 616–20. Bibcode:2003Sci...301..616H. doi:10.1126/science.1087619. PMID   12893936. S2CID   14078813.
  9. 1 2 Yan N (March 2013). "Structural advances for the major facilitator superfamily (MFS) transporters". Trends in Biochemical Sciences. 38 (3): 151–9. doi:10.1016/j.tibs.2013.01.003. PMID   23403214.
  10. 1 2 3 Kaback HR, Sahin-Tóth M, Weinglass AB (August 2001). "The kamikaze approach to membrane transport". Nature Reviews Molecular Cell Biology. 2 (8): 610–20. doi:10.1038/35085077. PMID   11483994. S2CID   31325451.
  11. 1 2 Sun J, Bankston JR, Payandeh J, Hinds TR, Zagotta WN, Zheng N (March 2014). "Crystal structure of the plant dual-affinity nitrate transporter NRT1.1". Nature. 507 (7490): 73–7. Bibcode:2014Natur.507...73S. doi:10.1038/nature13074. PMC   3968801 . PMID   24572362.
  12. ↑ Zheng H, Wisedchaisri G, Gonen T (May 2013). "Crystal structure of a nitrate/nitrite exchanger". Nature. 497 (7451): 647–51. Bibcode:2013Natur.497..647Z. doi:10.1038/nature12139. PMC   3669217 . PMID   23665960.
  13. ↑ Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE, Lodish HF (September 1985). "Sequence and structure of a human glucose transporter". Science. 229 (4717): 941–5. Bibcode:1985Sci...229..941M. doi:10.1126/science.3839598. PMID   3839598.
  14. ↑ Yan H, Huang W, Yan C, Gong X, Jiang S, Zhao Y, Wang J, Shi Y (March 2013). "Structure and mechanism of a nitrate transporter". Cell Reports. 3 (3): 716–23. doi: 10.1016/j.celrep.2013.03.007 . PMID   23523348.
  15. ↑ Tsay YF, Schroeder JI, Feldmann KA, Crawford NM (March 1993). "The herbicide sensitivity gene CHL1 of Arabidopsis encodes a nitrate-inducible nitrate transporter". Cell. 72 (5): 705–13. doi: 10.1016/0092-8674(93)90399-b . PMID   8453665.
  16. 1 2 Pedersen BP, Kumar H, Waight AB, Risenmay AJ, Roe-Zurz Z, Chau BH, Schlessinger A, Bonomi M, Harries W, Sali A, Johri AK, Stroud RM (April 2013). "Crystal structure of a eukaryotic phosphate transporter". Nature. 496 (7446): 533–6. Bibcode:2013Natur.496..533P. doi:10.1038/nature12042. PMC   3678552 . PMID   23542591.
  17. ↑ Doki S, Kato HE, Solcan N, Iwaki M, Koyama M, Hattori M, Iwase N, Tsukazaki T, Sugita Y, Kandori H, Newstead S, Ishitani R, Nureki O (July 2013). "Structural basis for dynamic mechanism of proton-coupled symport by the peptide transporter POT". Proceedings of the National Academy of Sciences of the United States of America. 110 (28): 11343–8. Bibcode:2013PNAS..11011343D. doi: 10.1073/pnas.1301079110 . PMC   3710879 . PMID   23798427.
  18. ↑ Jiang D, Zhao Y, Wang X, Fan J, Heng J, Liu X, Feng W, Kang X, Huang B, Liu J, Zhang XC (September 2013). "Structure of the YajR transporter suggests a transport mechanism based on the conserved motif A". Proceedings of the National Academy of Sciences of the United States of America. 110 (36): 14664–9. Bibcode:2013PNAS..11014664J. doi: 10.1073/pnas.1308127110 . PMC   3767500 . PMID   23950222.
  19. ↑ Putman M, van Veen HW, Konings WN (December 2000). "Molecular properties of bacterial multidrug transporters". Microbiology and Molecular Biology Reviews. 64 (4): 672–93. doi:10.1128/mmbr.64.4.672-693.2000. PMC   99009 . PMID   11104814.
  20. ↑ Yin Y, He X, Szewczyk P, Nguyen T, Chang G (May 2006). "Structure of the multidrug transporter EmrD from Escherichia coli". Science. 312 (5774): 741–4. Bibcode:2006Sci...312..741Y. doi:10.1126/science.1125629. PMC   3152482 . PMID   16675700.
  21. ↑ Li J, Shaikh SA, Enkavi G, Wen PC, Huang Z, Tajkhorshid E (May 2013). "Transient formation of water-conducting states in membrane transporters". Proceedings of the National Academy of Sciences of the United States of America. 110 (19): 7696–701. Bibcode:2013PNAS..110.7696L. doi: 10.1073/pnas.1218986110 . PMC   3651479 . PMID   23610412.
  22. ↑ Fischbarg J, Kuang KY, Vera JC, Arant S, Silverstein SC, Loike J, Rosen OM (April 1990). "Glucose transporters serve as water channels". Proceedings of the National Academy of Sciences of the United States of America. 87 (8): 3244–7. Bibcode:1990PNAS...87.3244F. doi: 10.1073/pnas.87.8.3244 . PMC   53872 . PMID   2326282.
  23. ↑ Dang S, Sun L, Huang Y, Lu F, Liu Y, Gong H, Wang J, Yan N (October 2010). "Structure of a fucose transporter in an outward-open conformation". Nature. 467 (7316): 734–8. Bibcode:2010Natur.467..734D. doi:10.1038/nature09406. PMID   20877283. S2CID   205222401.
  24. ↑ Kumar H, Kasho V, Smirnova I, Finer-Moore JS, Kaback HR, Stroud RM (February 2014). "Structure of sugar-bound LacY". Proceedings of the National Academy of Sciences of the United States of America. 111 (5): 1784–8. Bibcode:2014PNAS..111.1784K. doi: 10.1073/pnas.1324141111 . PMC   3918835 . PMID   24453216.
  25. ↑ Parker JL, Newstead S (March 2014). "Molecular basis of nitrate uptake by the plant nitrate transporter NRT1.1". Nature. 507 (7490): 68–72. Bibcode:2014Natur.507...68P. doi:10.1038/nature13116. PMC   3982047 . PMID   24572366.
  26. ↑ Deng D, Xu C, Sun P, Wu J, Yan C, Hu M, Yan N (June 2014). "Crystal structure of the human glucose transporter GLUT1". Nature. 510 (7503): 121–5. Bibcode:2014Natur.510..121D. doi:10.1038/nature13306. PMID   24847886. S2CID   205238604.
  27. ↑ Henderson PJ (Mar–Apr 1990). "The homologous glucose transport proteins of prokaryotes and eukaryotes". Research in Microbiology. 141 (3): 316–28. doi:10.1016/0923-2508(90)90005-b. PMID   2177911.
  28. ↑ Madej MG, Dang S, Yan N, Kaback HR (April 2013). "Evolutionary mix-and-match with MFS transporters". Proceedings of the National Academy of Sciences of the United States of America. 110 (15): 5870–4. Bibcode:2013PNAS..110.5870M. doi: 10.1073/pnas.1303538110 . PMC   3625355 . PMID   23530251.
  29. ↑ Madej MG, Kaback HR (December 2013). "Evolutionary mix-and-match with MFS transporters II". Proceedings of the National Academy of Sciences of the United States of America. 110 (50): E4831-8. Bibcode:2013PNAS..110E4831M. doi: 10.1073/pnas.1319754110 . PMC   3864288 . PMID   24259711.
  30. ↑ Västermark A, Lunt B, Saier M (2014). "Major facilitator superfamily porters, LacY, FucP and XylE of Escherichia coli appear to have evolved positionally dissimilar catalytic residues without rearrangement of 3-TMS repeat units". Journal of Molecular Microbiology and Biotechnology. 24 (2): 82–90. doi:10.1159/000358429. PMC   4048653 . PMID   24603210.
  31. ↑ Västermark A, Saier MH (April 2014). "Major Facilitator Superfamily (MFS) evolved without 3-transmembrane segment unit rearrangements". Proceedings of the National Academy of Sciences of the United States of America. 111 (13): E1162-3. Bibcode:2014PNAS..111E1162V. doi: 10.1073/pnas.1400016111 . PMC   3977298 . PMID   24567407.
  32. ↑ Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H (September 2000). "Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs". The Journal of Pharmacology and Experimental Therapeutics. 294 (3): 844–9. PMID   10945832.
  33. ↑ Fluman N, Bibi E (May 2009). "Bacterial multidrug transport through the lens of the major facilitator superfamily". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1794 (5): 738–47. doi:10.1016/j.bbapap.2008.11.020. PMID   19103310.
  34. ↑ Aldahmesh MA, Al-Hassnan ZN, Aldosari M, Alkuraya FS (October 2009). "Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: a common theme emerging". Neurogenetics. 10 (4): 307–11. doi:10.1007/s10048-009-0185-1. PMID   19277732. S2CID   36438803.
  35. 1 2 Meyer E, Ricketts C, Morgan NV, Morris MR, Pasha S, Tee LJ, Rahman F, Bazin A, Bessières B, Déchelotte P, Yacoubi MT, Al-Adnani M, Marton T, Tannahill D, Trembath RC, Fallet-Bianco C, Cox P, Williams D, Maher ER (March 2010). "Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome)". American Journal of Human Genetics. 86 (3): 471–8. doi:10.1016/j.ajhg.2010.02.004. PMC   2833392 . PMID   20206334.
  36. ↑ Pascual JM, Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC (May 2004). "GLUT1 deficiency and other glucose transporter diseases". European Journal of Endocrinology. 150 (5): 627–33. doi: 10.1530/eje.0.1500627 . PMID   15132717.
  37. ↑ Gerin I, Veiga-da-Cunha M, Achouri Y, Collet JF, Van Schaftingen E (December 1997). "Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib". FEBS Letters. 419 (2–3): 235–8. doi: 10.1016/s0014-5793(97)01463-4 . PMID   9428641. S2CID   31851796.
  38. ↑ Rajadhyaksha AM, Elemento O, Puffenberger EG, Schierberl KC, Xiang JZ, Putorti ML, Berciano J, Poulin C, Brais B, Michaelides M, Weleber RG, Higgins JJ (November 2010). "Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa". American Journal of Human Genetics. 87 (5): 643–54. doi:10.1016/j.ajhg.2010.10.013. PMC   2978959 . PMID   21070897.
  39. ↑ Lin P, Li J, Liu Q, Mao F, Li J, Qiu R, Hu H, Song Y, Yang Y, Gao G, Yan C, Yang W, Shao C, Gong Y (December 2008). "A missense mutation in SLC33A1, which encodes the acetyl-CoA transporter, causes autosomal-dominant spastic paraplegia (SPG42)". American Journal of Human Genetics. 83 (6): 752–9. doi:10.1016/j.ajhg.2008.11.003. PMC   2668077 . PMID   19061983.
  40. ↑ Verheijen FW, Verbeek E, Aula N, Beerens CE, Havelaar AC, Joosse M, Peltonen L, Aula P, Galjaard H, van der Spek PJ, Mancini GM (December 1999). "A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases". Nature Genetics. 23 (4): 462–5. doi:10.1038/70585. PMID   10581036. S2CID   5709302.
  41. ↑ Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, Fox JE, Mancini GM, Kambouris M, Gardella R, Facchetti F, Willems PJ, Forsyth R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A (April 2006). "Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome" (PDF). Nature Genetics. 38 (4): 452–7. doi:10.1038/ng1764. hdl: 11379/29243 . PMID   16550171. S2CID   836017.
  42. ↑ Vázquez-Mellado J, Jiménez-Vaca AL, Cuevas-Covarrubias S, Alvarado-Romano V, Pozo-Molina G, Burgos-Vargas R (February 2007). "Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout". Rheumatology. 46 (2): 215–9. doi: 10.1093/rheumatology/kel205 . PMID   16837472.
  43. ↑ Otonkoski T, Jiao H, Kaminen-Ahola N, Tapia-Paez I, Ullah MS, Parton LE, Schuit F, Quintens R, Sipilä I, Mayatepek E, Meissner T, Halestrap AP, Rutter GA, Kere J (September 2007). "Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells". American Journal of Human Genetics. 81 (3): 467–74. doi:10.1086/520960. PMC   1950828 . PMID   17701893.
  44. ↑ Burwinkel B, Kreuder J, Schweitzer S, Vorgerd M, Gempel K, Gerbitz KD, Kilimann MW (August 1999). "Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality". Biochemical and Biophysical Research Communications. 261 (2): 484–7. doi:10.1006/bbrc.1999.1060. PMID   10425211.
  45. ↑ Munroe PB, Mitchison HM, O'Rawe AM, Anderson JW, Boustany RM, Lerner TJ, Taschner PE, de Vos N, Breuning MH, Gardiner RM, Mole SE (August 1997). "Spectrum of mutations in the Batten disease gene, CLN3". American Journal of Human Genetics. 61 (2): 310–6. doi:10.1086/514846. PMC   1715900 . PMID   9311735.
  46. 1 2 Williams AL, Jacobs SB, Moreno-Macías H, Huerta-Chagoya A, Churchhouse C, Márquez-Luna C, García-Ortíz H, Gómez-Vázquez MJ, Burtt NP, Aguilar-Salinas CA, González-Villalpando C, Florez JC, Orozco L, Haiman CA, Tusié-Luna T, Altshuler D (February 2014). "Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico". Nature. 506 (7486): 97–101. Bibcode:2014Natur.506...97T. doi:10.1038/nature12828. PMC   4127086 . PMID   24390345.
  47. ↑ Matsuo H, Chiba T, Nagamori S, Nakayama A, Domoto H, Phetdee K, Wiriyasermkul P, Kikuchi Y, Oda T, Nishiyama J, Nakamura T, Morimoto Y, Kamakura K, Sakurai Y, Nonoyama S, Kanai Y, Shinomiya N (December 2008). "Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia". American Journal of Human Genetics. 83 (6): 744–51. doi:10.1016/j.ajhg.2008.11.001. PMC   2668068 . PMID   19026395.
  48. ↑ Zeng WQ, Al-Yamani E, Acierno JS, Slaugenhaupt S, Gillis T, MacDonald ME, Ozand PT, Gusella JF (July 2005). "Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3". American Journal of Human Genetics. 77 (1): 16–26. doi:10.1086/431216. PMC   1226189 . PMID   15871139.
  49. ↑ Kloeckener-Gruissem B, Vandekerckhove K, Nürnberg G, Neidhardt J, Zeitz C, Nürnberg P, Schipper I, Berger W (March 2008). "Mutation of solute carrier SLC16A12 associates with a syndrome combining juvenile cataract with microcornea and renal glucosuria". American Journal of Human Genetics. 82 (3): 772–9. doi:10.1016/j.ajhg.2007.12.013. PMC   2427214 . PMID   18304496.
  50. ↑ Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, Szargel R, McDonald L, Shalata A, Nosaka K, Gregory S, Cohen N (July 1999). "Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness". Nature Genetics. 22 (3): 300–4. doi:10.1038/10372. PMID   10391221. S2CID   26615141.
  51. ↑ Kousi M, Siintola E, Dvorakova L, Vlaskova H, Turnbull J, Topcu M, Yuksel D, Gokben S, Minassian BA, Elleder M, Mole SE, Lehesjoki AE (March 2009). "Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis". Brain. 132 (Pt 3): 810–9. doi: 10.1093/brain/awn366 . PMID   19201763.
  52. ↑ Zaahl MG, Merryweather-Clarke AT, Kotze MJ, van der Merwe S, Warnich L, Robson KJ (October 2004). "Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload". Human Genetics. 115 (5): 409–17. doi:10.1007/s00439-004-1166-y. PMID   15338274. S2CID   22266373.
  53. ↑ Kusari J, Verma US, Buse JB, Henry RR, Olefsky JM (October 1991). "Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus". The Journal of Clinical Investigation. 88 (4): 1323–30. doi:10.1172/JCI115437. PMC   295602 . PMID   1918382.
  54. ↑ Newton JM, Cohen-Barak O, Hagiwara N, Gardner JM, Davisson MT, King RA, Brilliant MH (November 2001). "Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4". American Journal of Human Genetics. 69 (5): 981–8. doi:10.1086/324340. PMC   1274374 . PMID   11574907.
  55. ↑ Seifert W, Kühnisch J, Tüysüz B, Specker C, Brouwers A, Horn D (April 2012). "Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing". Human Mutation. 33 (4): 660–4. doi:10.1002/humu.22042. PMID   22331663. S2CID   24703466.
  56. ↑ Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, Furukawa H, Nagashima M, Yoshino S, Mabuchi A, Sekine A, Saito S, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K (December 2003). "An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis". Nature Genetics. 35 (4): 341–8. doi:10.1038/ng1267. PMID   14608356. S2CID   21564858.
  57. 1 2 van de Steeg E, Stránecký V, Hartmannová H, Nosková L, Hřebíček M, Wagenaar E, van Esch A, de Waart DR, Oude Elferink RP, Kenworthy KE, Sticová E, al-Edreesi M, Knisely AS, Kmoch S, Jirsa M, Schinkel AH (February 2012). "Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver". The Journal of Clinical Investigation. 122 (2): 519–28. doi:10.1172/JCI59526. PMC   3266790 . PMID   22232210.
  58. ↑ Sakamoto O, Ogawa E, Ohura T, Igarashi Y, Matsubara Y, Narisawa K, Iinuma K (November 2000). "Mutation analysis of the GLUT2 gene in patients with Fanconi-Bickel syndrome". Pediatric Research. 48 (5): 586–9. doi: 10.1203/00006450-200011000-00005 . PMID   11044475.
  59. ↑ Wang D, Kranz-Eble P, De Vivo DC (September 2000). "Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome". Human Mutation. 16 (3): 224–31. doi: 10.1002/1098-1004(200009)16:3<224::AID-HUMU5>3.0.CO;2-P . PMID   10980529.
  60. ↑ Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID (December 2006). "Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption". Cell. 127 (5): 917–28. doi: 10.1016/j.cell.2006.09.041 . PMID   17129779. S2CID   1918658.
  61. ↑ Ruel J, Emery S, Nouvian R, Bersot T, Amilhon B, Van Rybroek JM, Rebillard G, Lenoir M, Eybalin M, Delprat B, Sivakumaran TA, Giros B, El Mestikawy S, Moser T, Smith RJ, Lesperance MM, Puel JL (August 2008). "Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice". American Journal of Human Genetics. 83 (2): 278–92. doi:10.1016/j.ajhg.2008.07.008. PMC   2495073 . PMID   18674745.
  62. 1 2 3 4 Perland E, Fredriksson R (March 2017). "Classification Systems of Secondary Active Transporters". Trends in Pharmacological Sciences. 38 (3): 305–315. doi:10.1016/j.tips.2016.11.008. PMID   27939446.
  63. ↑ Hediger MA, Clémençon B, Burrier RE, Bruford EA (2017-06-01). "The ABCs of membrane transporters in health and disease (SLC series): introduction". Molecular Aspects of Medicine. 34 (2–3): 95–107. doi:10.1016/j.mam.2012.12.009. PMC   3853582 . PMID   23506860.
  64. 1 2 3 Perland E, Lekholm E, Eriksson MM, Bagchi S, Arapi V, Fredriksson R (2016-01-01). "The Putative SLC Transporters Mfsd5 and Mfsd11 Are Abundantly Expressed in the Mouse Brain and Have a Potential Role in Energy Homeostasis". PLOS ONE. 11 (6): e0156912. Bibcode:2016PLoSO..1156912P. doi: 10.1371/journal.pone.0156912 . PMC   4896477 . PMID   27272503.
  65. 1 2 3 4 5 6 Sreedharan S, Stephansson O, Schiöth HB, Fredriksson R (June 2011). "Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters". Gene. 478 (1–2): 11–8. doi:10.1016/j.gene.2010.10.011. PMID   21044875.
  66. 1 2 3 Perland E, Hellsten SV, Lekholm E, Eriksson MM, Arapi V, Fredriksson R (February 2017). "The Novel Membrane-Bound Proteins MFSD1 and MFSD3 are Putative SLC Transporters Affected by Altered Nutrient Intake". Journal of Molecular Neuroscience. 61 (2): 199–214. doi:10.1007/s12031-016-0867-8. PMC   5321710 . PMID   27981419.
  67. ↑ Gray KA, Seal RL, Tweedie S, Wright MW, Bruford EA (February 2016). "A review of the new HGNC gene family resource". Human Genomics. 10: 6. doi: 10.1186/s40246-016-0062-6 . PMC   4739092 . PMID   26842383.
  68. ↑ Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, Wenk MR, Goh EL, Silver DL (May 2014). "Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid". Nature. 509 (7501): 503–6. Bibcode:2014Natur.509..503N. doi:10.1038/nature13241. PMID   24828044. S2CID   4462512.
  69. 1 2 Perland E, Hellsten SV, Schweizer N, Arapi V, Rezayee F, Bushra M, Fredriksson R (2017). "Structural prediction of two novel human atypical SLC transporters, MFSD4A and MFSD9, and their neuroanatomical distribution in mice". PLOS ONE. 12 (10): e0186325. Bibcode:2017PLoSO..1286325P. doi: 10.1371/journal.pone.0186325 . PMC   5648162 . PMID   29049335.
  70. ↑ Horiba N, Masuda S, Ohnishi C, Takeuchi D, Okuda M, Inui K (July 2003). "Na(+)-dependent fructose transport via rNaGLT1 in rat kidney". FEBS Letters. 546 (2–3): 276–80. doi: 10.1016/s0014-5793(03)00600-8 . PMID   12832054. S2CID   27361236.
  71. ↑ Damme M, Brandenstein L, Fehr S, Jankowiak W, Bartsch U, Schweizer M, Hermans-Borgmeyer I, Storch S (May 2014). "Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease". Neurobiology of Disease. 65: 12–24. doi:10.1016/j.nbd.2014.01.003. PMID   24423645. S2CID   207068059.
  72. ↑ Ushijima H, Hiasa M, Namba T, Hwang HJ, Hoshino T, Mima S, Tsuchiya T, Moriyama Y, Mizushima T (September 2008). "Expression and function of TETRAN, a new type of membrane transporter". Biochemical and Biophysical Research Communications. 374 (2): 325–30. doi:10.1016/j.bbrc.2008.07.034. PMID   18638446.
  73. 1 2 Lekholm E, Perland E, Eriksson MM, Hellsten SV, Lindberg FA, Rostami J, Fredriksson R (2017-01-01). "Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability". Frontiers in Molecular Neuroscience. 10: 11. doi: 10.3389/fnmol.2017.00011 . PMC   5263138 . PMID   28179877.
  74. ↑ Ceder MM, Lekholm E, Hellsten SV, Perland E, Fredriksson R (2017). "The Neuronal and Peripheral Expressed Membrane-Bound UNC93A Respond to Nutrient Availability in Mice". Frontiers in Molecular Neuroscience. 10: 351. doi: 10.3389/fnmol.2017.00351 . PMC   5671512 . PMID   29163028.
  75. ↑ Campbell CL, Lehmann CJ, Gill SS, Dunn WA, James AA, Foy BD (August 2011). "A role for endosomal proteins in alphavirus dissemination in mosquitoes". Insect Molecular Biology. 20 (4): 429–36. doi:10.1111/j.1365-2583.2011.01078.x. PMC   3138809 . PMID   21496127.
  76. ↑ Ceder MM, Aggarwal T, Hosseini K, Maturi V, Patil S, Perland E, et al. (2020). "CG4928 Is Vital for Renal Function in Fruit Flies and Membrane Potential in Cells: A First In-Depth Characterization of the Putative Solute Carrier UNC93A". Frontiers in Cell and Developmental Biology. 8: 580291. doi: 10.3389/fcell.2020.580291 . PMC   7591606 . PMID   33163493.
  77. ↑ Tabeta K, Hoebe K, Janssen EM, Du X, Georgel P, Crozat K, Mudd S, Mann N, Sovath S, Goode J, Shamel L, Herskovits AA, Portnoy DA, Cooke M, Tarantino LM, Wiltshire T, Steinberg BE, Grinstein S, Beutler B (February 2006). "The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9". Nature Immunology. 7 (2): 156–64. doi:10.1038/ni1297. PMID   16415873. S2CID   33401155.
  78. ↑ Yanagisawa H, Miyashita T, Nakano Y, Yamamoto D (July 2003). "HSpin1, a transmembrane protein interacting with Bcl-2/Bcl-xL, induces a caspase-independent autophagic cell death". Cell Death and Differentiation. 10 (7): 798–807. doi: 10.1038/sj.cdd.4401246 . PMID   12815463.
  79. ↑ Storch S, Pohl S, Quitsch A, Falley K, Braulke T (April 2007). "C-terminal prenylation of the CLN3 membrane glycoprotein is required for efficient endosomal sorting to lysosomes". Traffic. 8 (4): 431–44. doi: 10.1111/j.1600-0854.2007.00537.x . PMID   17286803. S2CID   31146043.
  80. ↑ Perland E, Bagchi S, Klaesson A, Fredriksson R (September 2017). "Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression". Open Biology. 7 (9): 170142. doi:10.1098/rsob.170142. PMC   5627054 . PMID   28878041.
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