Biology:Major facilitator superfamily

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Major Facilitator Superfamily
2y5y.png
Crystal Structure of Lactose Permease LacY.
Identifiers
SymbolMFS
Pfam clanCL0015
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

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.

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

File:GlpT rotate.webm

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 be 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.[60] There are today 52 SLC families,[61] 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.[60] Atypical SLCs are MFS proteins, sharing sequence similarities and evolutionary origin with SLCs,[60][62][63][64] but they are not named according to the SLC root system, which originates from the hugo gene nomenclature system (HGNC).[65] All atypical SLCs are listed in detail in,[60] but they are: MFSD1,[64] MFSD2A,[66] MFSD2B, MFSD3,[64] MFSD4A,[67] MFSD4B,[68] MFSD5,[62] MFSD6,[63] MFSD6L, MFSD8,[69] MFSD9,[63][67] MFSD10,[63][70] MFSD11,[62] MFSD12, MFSD13A, MFSD14A,[63][71] MFSD14B,[63][71] UNC93A,[72][73][74] UNC93B1,[75] SV2A, SV2B, SV2C, SVOP, SVOPL, SPNS1,[76] SPNS2, SPNS3 and CLN3.[77] 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.[78]

References

  1. ↑ "Major facilitator superfamily". Microbiology and Molecular Biology Reviews 62 (1): 1–34. March 1998. doi:10.1128/MMBR.62.1.1-34.1998. PMID 9529885. 
  2. ↑ "Sugar transporters from bacteria, parasites and mammals: structure-activity relationships". Trends in Biochemical Sciences 23 (12): 476–81. December 1998. doi:10.1016/S0968-0004(98)01326-7. PMID 9868370. 
  3. ↑ "A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport". Trends in Biochemical Sciences 18 (1): 13–20. January 1993. doi:10.1016/0968-0004(93)90081-w. PMID 8438231. 
  4. ↑ "Structure of the lac carrier protein of Escherichia coli". The Journal of Biological Chemistry 258 (1): 31–4. January 1983. doi:10.1016/S0021-9258(18)33213-7. PMID 6336750. 
  5. ↑ "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. April 1996. doi:10.1073/pnas.93.8.3630. PMID 8622987. Bibcode: 1996PNAS...93.3630P. 
  6. ↑ "Mammalian and bacterial sugar transport proteins are homologous". Nature 325 (6105): 641–3. Feb 12–18, 1987. doi:10.1038/325641a0. PMID 3543693. Bibcode: 1987Natur.325..641M. 
  7. ↑ 7.0 7.1 7.2 "Structure and mechanism of the lactose permease of Escherichia coli". Science 301 (5633): 610–5. August 2003. doi:10.1126/science.1088196. PMID 12893935. Bibcode: 2003Sci...301..610A. 
  8. ↑ 8.0 8.1 8.2 "Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli". Science 301 (5633): 616–20. August 2003. doi:10.1126/science.1087619. PMID 12893936. Bibcode: 2003Sci...301..616H. 
  9. ↑ 9.0 9.1 "Structural advances for the major facilitator superfamily (MFS) transporters". Trends in Biochemical Sciences 38 (3): 151–9. March 2013. doi:10.1016/j.tibs.2013.01.003. PMID 23403214. 
  10. ↑ 10.0 10.1 10.2 "The kamikaze approach to membrane transport". Nature Reviews Molecular Cell Biology 2 (8): 610–20. August 2001. doi:10.1038/35085077. PMID 11483994. 
  11. ↑ 11.0 11.1 "Crystal structure of the plant dual-affinity nitrate transporter NRT1.1". Nature 507 (7490): 73–7. March 2014. doi:10.1038/nature13074. PMID 24572362. Bibcode: 2014Natur.507...73S. 
  12. ↑ "Crystal structure of a nitrate/nitrite exchanger". Nature 497 (7451): 647–51. May 2013. doi:10.1038/nature12139. PMID 23665960. Bibcode: 2013Natur.497..647Z. 
  13. ↑ "Sequence and structure of a human glucose transporter". Science 229 (4717): 941–5. September 1985. doi:10.1126/science.3839598. PMID 3839598. Bibcode: 1985Sci...229..941M. 
  14. ↑ "Structure and mechanism of a nitrate transporter". Cell Reports 3 (3): 716–23. March 2013. doi:10.1016/j.celrep.2013.03.007. PMID 23523348. 
  15. ↑ "The herbicide sensitivity gene CHL1 of Arabidopsis encodes a nitrate-inducible nitrate transporter". Cell 72 (5): 705–13. March 1993. doi:10.1016/0092-8674(93)90399-b. PMID 8453665. 
  16. ↑ 16.0 16.1 "Crystal structure of a eukaryotic phosphate transporter". Nature 496 (7446): 533–6. April 2013. doi:10.1038/nature12042. PMID 23542591. Bibcode: 2013Natur.496..533P. 
  17. ↑ "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. July 2013. doi:10.1073/pnas.1301079110. PMID 23798427. Bibcode: 2013PNAS..11011343D. 
  18. ↑ "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. September 2013. doi:10.1073/pnas.1308127110. PMID 23950222. Bibcode: 2013PNAS..11014664J. 
  19. ↑ "Molecular properties of bacterial multidrug transporters". Microbiology and Molecular Biology Reviews 64 (4): 672–93. December 2000. doi:10.1128/mmbr.64.4.672-693.2000. PMID 11104814. 
  20. ↑ "Structure of the multidrug transporter EmrD from Escherichia coli". Science 312 (5774): 741–4. May 2006. doi:10.1126/science.1125629. PMID 16675700. Bibcode: 2006Sci...312..741Y. 
  21. ↑ "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. May 2013. doi:10.1073/pnas.1218986110. PMID 23610412. Bibcode: 2013PNAS..110.7696L. 
  22. ↑ "Glucose transporters serve as water channels". Proceedings of the National Academy of Sciences of the United States of America 87 (8): 3244–7. April 1990. doi:10.1073/pnas.87.8.3244. PMID 2326282. Bibcode: 1990PNAS...87.3244F. 
  23. ↑ "Structure of a fucose transporter in an outward-open conformation". Nature 467 (7316): 734–8. October 2010. doi:10.1038/nature09406. PMID 20877283. Bibcode: 2010Natur.467..734D. 
  24. ↑ "Structure of sugar-bound LacY". Proceedings of the National Academy of Sciences of the United States of America 111 (5): 1784–8. February 2014. doi:10.1073/pnas.1324141111. PMID 24453216. Bibcode: 2014PNAS..111.1784K. 
  25. ↑ "Molecular basis of nitrate uptake by the plant nitrate transporter NRT1.1". Nature 507 (7490): 68–72. March 2014. doi:10.1038/nature13116. PMID 24572366. Bibcode: 2014Natur.507...68P. 
  26. ↑ "Crystal structure of the human glucose transporter GLUT1". Nature 510 (7503): 121–5. June 2014. doi:10.1038/nature13306. PMID 24847886. Bibcode: 2014Natur.510..121D. 
  27. ↑ "The homologous glucose transport proteins of prokaryotes and eukaryotes". Research in Microbiology 141 (3): 316–28. Mar–Apr 1990. doi:10.1016/0923-2508(90)90005-b. PMID 2177911. 
  28. ↑ "Evolutionary mix-and-match with MFS transporters". Proceedings of the National Academy of Sciences of the United States of America 110 (15): 5870–4. April 2013. doi:10.1073/pnas.1303538110. PMID 23530251. Bibcode: 2013PNAS..110.5870M. 
  29. ↑ "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. December 2013. doi:10.1073/pnas.1319754110. PMID 24259711. Bibcode: 2013PNAS..110E4831M. 
  30. ↑ "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. 2014. doi:10.1159/000358429. PMID 24603210. 
  31. ↑ "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. April 2014. doi:10.1073/pnas.1400016111. PMID 24567407. Bibcode: 2014PNAS..111E1162V. 
  32. ↑ "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. September 2000. PMID 10945832. 
  33. ↑ "Bacterial multidrug transport through the lens of the major facilitator superfamily". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1794 (5): 738–47. May 2009. doi:10.1016/j.bbapap.2008.11.020. PMID 19103310. 
  34. ↑ "Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: a common theme emerging". Neurogenetics 10 (4): 307–11. October 2009. doi:10.1007/s10048-009-0185-1. PMID 19277732. 
  35. ↑ 35.0 35.1 "Mutations in FLVCR2 are associated with proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (Fowler syndrome)". American Journal of Human Genetics 86 (3): 471–8. March 2010. doi:10.1016/j.ajhg.2010.02.004. PMID 20206334. 
  36. ↑ "GLUT1 deficiency and other glucose transporter diseases". European Journal of Endocrinology 150 (5): 627–33. May 2004. doi:10.1530/eje.0.1500627. PMID 15132717. 
  37. ↑ "Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib". FEBS Letters 419 (2–3): 235–8. December 1997. doi:10.1016/s0014-5793(97)01463-4. PMID 9428641. 
  38. ↑ "Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa". American Journal of Human Genetics 87 (5): 643–54. November 2010. doi:10.1016/j.ajhg.2010.10.013. PMID 21070897. 
  39. ↑ "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. December 2008. doi:10.1016/j.ajhg.2008.11.003. PMID 19061983. 
  40. ↑ "A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases". Nature Genetics 23 (4): 462–5. December 1999. doi:10.1038/70585. PMID 10581036. 
  41. ↑ "Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome". Nature Genetics 38 (4): 452–7. April 2006. doi:10.1038/ng1764. PMID 16550171. https://iris.unibs.it/bitstream/11379/29243/1/NAT.GEN-06.pdf. 
  42. ↑ "Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout". Rheumatology 46 (2): 215–9. February 2007. doi:10.1093/rheumatology/kel205. PMID 16837472. 
  43. ↑ "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. September 2007. doi:10.1086/520960. PMID 17701893. 
  44. ↑ "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. August 1999. doi:10.1006/bbrc.1999.1060. PMID 10425211. 
  45. ↑ "Spectrum of mutations in the Batten disease gene, CLN3". American Journal of Human Genetics 61 (2): 310–6. August 1997. doi:10.1086/514846. PMID 9311735. 
  46. ↑ "Mutations in glucose transporter 9 gene SLC2A9 cause renal hypouricemia". American Journal of Human Genetics 83 (6): 744–51. December 2008. doi:10.1016/j.ajhg.2008.11.001. PMID 19026395. 
  47. ↑ "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. July 2005. doi:10.1086/431216. PMID 15871139. 
  48. ↑ "Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness". Nature Genetics 22 (3): 300–4. July 1999. doi:10.1038/10372. PMID 10391221. 
  49. ↑ "Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis". Brain 132 (Pt 3): 810–9. March 2009. doi:10.1093/brain/awn366. PMID 19201763. 
  50. ↑ "Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload". Human Genetics 115 (5): 409–17. October 2004. doi:10.1007/s00439-004-1166-y. PMID 15338274. 
  51. ↑ "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. October 1991. doi:10.1172/JCI115437. PMID 1918382. 
  52. ↑ "Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing". Human Mutation 33 (4): 660–4. April 2012. doi:10.1002/humu.22042. PMID 22331663. 
  53. ↑ "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. December 2003. doi:10.1038/ng1267. PMID 14608356. 
  54. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named 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 97–101
  55. ↑ 55.0 55.1 "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. February 2012. doi:10.1172/JCI59526. PMID 22232210. 
  56. ↑ "Mutation analysis of the GLUT2 gene in patients with Fanconi-Bickel syndrome". Pediatric Research 48 (5): 586–9. November 2000. doi:10.1203/00006450-200011000-00005. PMID 11044475. 
  57. ↑ "Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome". Human Mutation 16 (3): 224–31. September 2000. doi:10.1002/1098-1004(200009)16:3<224::AID-HUMU5>3.0.CO;2-P. PMID 10980529. 
  58. ↑ "Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption". Cell 127 (5): 917–28. December 2006. doi:10.1016/j.cell.2006.09.041. PMID 17129779. 
  59. ↑ "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. August 2008. doi:10.1016/j.ajhg.2008.07.008. PMID 18674745. 
  60. ↑ 60.0 60.1 60.2 60.3 "Classification Systems of Secondary Active Transporters". Trends in Pharmacological Sciences 38 (3): 305–315. March 2017. doi:10.1016/j.tips.2016.11.008. PMID 27939446. 
  61. ↑ "The ABCs of membrane transporters in health and disease (SLC series): introduction". Molecular Aspects of Medicine 34 (2–3): 95–107. 2017-06-01. doi:10.1016/j.mam.2012.12.009. PMID 23506860. 
  62. ↑ 62.0 62.1 62.2 "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. 2016-01-01. doi:10.1371/journal.pone.0156912. PMID 27272503. Bibcode: 2016PLoSO..1156912P. 
  63. ↑ 63.0 63.1 63.2 63.3 63.4 63.5 "Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters". Gene 478 (1–2): 11–8. June 2011. doi:10.1016/j.gene.2010.10.011. PMID 21044875. 
  64. ↑ 64.0 64.1 64.2 "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. February 2017. doi:10.1007/s12031-016-0867-8. PMID 27981419. 
  65. ↑ "A review of the new HGNC gene family resource". Human Genomics 10: 6. February 2016. doi:10.1186/s40246-016-0062-6. PMID 26842383. 
  66. ↑ "Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid". Nature 509 (7501): 503–6. May 2014. doi:10.1038/nature13241. PMID 24828044. Bibcode: 2014Natur.509..503N. 
  67. ↑ 67.0 67.1 "Structural prediction of two novel human atypical SLC transporters, MFSD4A and MFSD9, and their neuroanatomical distribution in mice". PLOS ONE 12 (10): e0186325. 2017. doi:10.1371/journal.pone.0186325. PMID 29049335. Bibcode: 2017PLoSO..1286325P. 
  68. ↑ "Na(+)-dependent fructose transport via rNaGLT1 in rat kidney". FEBS Letters 546 (2–3): 276–80. July 2003. doi:10.1016/s0014-5793(03)00600-8. PMID 12832054. 
  69. ↑ "Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease". Neurobiology of Disease 65: 12–24. May 2014. doi:10.1016/j.nbd.2014.01.003. PMID 24423645. 
  70. ↑ "Expression and function of TETRAN, a new type of membrane transporter". Biochemical and Biophysical Research Communications 374 (2): 325–30. September 2008. doi:10.1016/j.bbrc.2008.07.034. PMID 18638446. 
  71. ↑ 71.0 71.1 "Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability". Frontiers in Molecular Neuroscience 10: 11. 2017-01-01. doi:10.3389/fnmol.2017.00011. PMID 28179877. 
  72. ↑ "The Neuronal and Peripheral Expressed Membrane-Bound UNC93A Respond to Nutrient Availability in Mice" (in en). Frontiers in Molecular Neuroscience 10: 351. 2017. doi:10.3389/fnmol.2017.00351. PMID 29163028. 
  73. ↑ "A role for endosomal proteins in alphavirus dissemination in mosquitoes". Insect Molecular Biology 20 (4): 429–36. August 2011. doi:10.1111/j.1365-2583.2011.01078.x. PMID 21496127. 
  74. ↑ "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. 2020. doi:10.3389/fcell.2020.580291. PMID 33163493. 
  75. ↑ "The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9". Nature Immunology 7 (2): 156–64. February 2006. doi:10.1038/ni1297. PMID 16415873. 
  76. ↑ "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. July 2003. doi:10.1038/sj.cdd.4401246. PMID 12815463. 
  77. ↑ "C-terminal prenylation of the CLN3 membrane glycoprotein is required for efficient endosomal sorting to lysosomes". Traffic 8 (4): 431–44. April 2007. doi:10.1111/j.1600-0854.2007.00537.x. PMID 17286803. 
  78. ↑ "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. September 2017. doi:10.1098/rsob.170142. PMID 28878041. 



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