Major facilitator superfamily

From Wikipedia the free encyclopedia

Major Facilitator Superfamily
Crystal Structure of Lactose Permease LacY.
Identifiers
SymbolMFS
Pfam clanCL0015
ECOD5050.1.1
TCDB2.A.1
OPM superfamily15
CDDcd06174

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]

Function

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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

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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

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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.

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

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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

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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

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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

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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

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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

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

Human MFS proteins

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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]

References

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  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. ^ a b c 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. ^ a b c 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. ^ a b 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. ^ a b c 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b 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. ^ a b c d 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. ^ a b c 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. ^ a b c d e f 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. ^ a b c 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. ^ a b 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. ^ a b 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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