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Solute carrier family

From Wikipedia, the free encyclopedia

The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families.[1][2] 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.

Solutes that are transported by the various SLC group members are extremely diverse and include both charged and uncharged organic molecules as well as inorganic ions and the gas ammonia.

As is typical of integral membrane proteins, SLCs contain a number of hydrophobic transmembrane alpha helices connected to each other by hydrophilic intra- and extra-cellular loops. Depending on the SLC, these transporters are functional as either monomers or obligate homo- or hetero-oligomers. Many SLC families are members of the major facilitator superfamily.

Scope

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By convention of the nomenclature system, members within an individual SLC family have greater than 20-25% sequence identity to each other. In contrast, the homology between SLC families is very low to non-existent.[3] Hence, the criteria for inclusion of a family into the SLC group is not evolutionary relatedness to other SLC families but rather functional (i.e., an integral membrane protein that transports a solute).

The SLC group include examples of transport proteins that are:

The SLC series does not include members of transport protein families that have previously been classified by other widely accepted nomenclature systems including:

Subcellular distribution

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Most members of the SLC group are located in the cell membrane, but some members are located in mitochondria (the most notable one being SLC family 25) or other intracellular organelles.

Nomenclature system

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Names of individual SLC members have the following format:[4]

where:

  • SLC is the root name (SoLute Carrier)
  • n = an integer representing a family (e.g., 1-52)
  • X = a single letter (A, B, C, ...) denoting a subfamily
  • m = an integer representing an individual family member (isoform).

For example, SLC1A1 is the first isoform of subfamily A of SLC family 1.

An exception occurs with SLC family 21[5] (the organic anion transporting polypeptide transporters), which for historical reasons have names in the format SLCOnXm where n = family number, X = subfamily letter, and m = member number.

While the HGNC only assign nomenclature to human genes, by convention vertebrate orthologs of these genes adopt the same nomenclature (e.g., VGNC-assigned orthologs of SLC10A1). For rodents, the case of the symbols differs from other vertebrates by using title case, i.e. Slc1a1 denotes the rodent ortholog of the human SLC1A1 gene.

Families

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The following families are named under SLC:[6]

  1. high-affinity glutamate and neutral amino acid transporter[7]
  2. facilitative GLUT transporter[8]
  3. heavy subunits of heterodimeric amino acid transporters[9]
  4. bicarbonate transporter[10]
  5. sodium glucose cotransporter[11]
  6. sodium- and chloride-dependent sodium:neurotransmitter symporters[12]
  7. cationic amino acid transporter/glycoprotein-associated[13]
  8. Na+/Ca2+ exchanger[14]
  9. Na+/H+ exchanger[15]
  10. sodium bile salt cotransport[16]
  11. proton coupled metal ion transporter[17]
  12. electroneutral cation-Cl cotransporter[18]
  13. Na+-sulfate/carboxylate cotransporter[19]
  14. urea transporter[20]
  15. proton oligopeptide cotransporter[21]
  16. monocarboxylate transporter[22]
  17. vesicular glutamate transporter[23]
  18. vesicular amine transporter[24]
  19. folate/thiamine transporter[25]
  20. type III Na+-phosphate cotransporter[26]
  21. organic anion transporting[27]
  22. organic cation/anion/zwitterion transporter[28]
  23. Na+-dependent ascorbic acid transporter[29]
  24. Na+/(Ca2+-K+) exchanger[30]
  25. mitochondrial carrier[31]
  26. multifunctional anion exchanger[32]
  27. fatty acid transport proteins[33]
  28. Na+-coupled nucleoside transport[34]
  29. facilitative nucleoside transporter[35]
  30. zinc transporter[36]
  31. copper transporter[37]
  32. vesicular inhibitory amino acid transporter[38]
  33. Acetyl-CoA transporter[39]
  34. type II Na+-phosphate cotransporter[40]
  35. nucleotide-sugar transporter[41]
  36. proton-coupled amino acid transporter[42]
  37. sugar-phosphate/phosphate exchanger[43]
  38. System A & N, sodium-coupled neutral amino acid transporter[44]
  39. metal ion transporter[45]
  40. basolateral iron transporter[46]
  41. MgtE-like magnesium transporter
  42. Ammonia transporter[47][48]
  43. Na+-independent, system-L like amino acid transporter
  44. Choline-like transporter
  45. Putative sugar transporter
  46. Folate transporter
  47. multidrug and toxin extrusion
  48. Heme transporter family
    • (SLC48A1)
  49. Heme transporter
  50. Sugar efflux transporters of the SWEET family
  51. Transporters of steroid-derived molecules
  52. Riboflavin transporter family RFVT/SLC52
  53. Phosphate carriers
  54. Mitochondrial pyruvate carriers
  55. Mitochondrial cation/proton exchangers
  56. Sideroflexins
  57. NiPA-like magnesium transporter family
  58. MagT-like magnesium transporter family
  59. Sodium-dependent lysophosphatidylcholine symporter family
  60. Glucose transporters
  61. Molybdate transporter family
  62. Pyrophosphate transporters
  63. Sphingosine-phosphate transporters
  64. Golgi Ca2+/H+ exchangers
  65. NPC-type cholesterol transporters
  66. Cationic amino acid exporters

Putative SLCs

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Putative SLCs, also called atypical SLCs, are novel, plausible secondary active or facilitative transporter proteins that share ancestral background with the known SLCs. [2][49] The atypical SLCs of MFS type can, however, be subdivided into 15 Putative MFS Transporter Families (AMTF).[49]

All the putative SLCs are plausible SLC transporters. Some are only "atypical" when it comes to their nomenclature; the genes have an SLC assignment but as an alias, and have retained their already assigned "non-SLC" gene symbol as the approved symbol.

Here are some Putative SLCs listed: OCA2, CLN3, TMEM104, SPNS1, SPNS2, SPNS3, SV2A, SV2B, SV2C, SVOP, SVOPL, MFSD1,[50] MFSD2A, MFSD2B, MFSD3,[50] MFSD4A,[51] MFSD4B, MFSD5,[52] MFSD6, MFSD6L, MFSD8, MFSD9,[51] MFSD10, MFSD11,[52] MFSD12, MFSD13A, MFSD14A,[53] MFSD14B,[53] UNC93A[54][55] and UNC93B1.

References

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  1. ^ Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA (February 2004). "The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction". Pflügers Archiv. 447 (5): 465–468. doi:10.1007/s00424-003-1192-y. PMID 14624363. S2CID 1866661.
  2. ^ a b 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.
  3. ^ Höglund PJ, Nordström KJ, Schiöth HB, Fredriksson R (April 2011). "The solute carrier families have a remarkably long evolutionary history with the majority of the human families present before divergence of Bilaterian species". Molecular Biology and Evolution. 28 (4): 1531–1541. doi:10.1093/molbev/msq350. PMC 3058773. PMID 21186191.
  4. ^ Hediger MA, Clémençon B, Burrier RE, Bruford EA (2013). "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.
  5. ^ He L, Vasiliou K, Nebert DW (January 2009). "Analysis and update of the human solute carrier (SLC) gene superfamily". Human Genomics. 3 (2): 195–206. doi:10.1186/1479-7364-3-2-195. PMC 2752037. PMID 19164095.
  6. ^ "SLCtables". slc.bioparadigms.org. Retrieved 2018-03-07.
  7. ^ Kanai Y, Hediger MA (February 2004). "The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects". Pflügers Archiv. 447 (5): 469–479. doi:10.1007/s00424-003-1146-4. PMID 14530974. S2CID 21564906.
  8. ^ Uldry M, Thorens B (February 2004). "The SLC2 family of facilitated hexose and polyol transporters". Pflügers Archiv. 447 (5): 480–489. doi:10.1007/s00424-003-1085-0. PMID 12750891. S2CID 25539725.
  9. ^ Palacín M, Kanai Y (February 2004). "The ancillary proteins of HATs: SLC3 family of amino acid transporters". Pflügers Archiv. 447 (5): 490–494. doi:10.1007/s00424-003-1062-7. PMID 14770309. S2CID 25808108.
  10. ^ Romero MF, Fulton CM, Boron WF (February 2004). "The SLC4 family of HCO 3 - transporters". Pflügers Archiv. 447 (5): 495–509. doi:10.1007/s00424-003-1180-2. PMID 14722772. S2CID 40609789.
  11. ^ Wright EM, Turk E (February 2004). "The sodium/glucose cotransport family SLC5". Pflügers Archiv. 447 (5): 510–518. doi:10.1007/s00424-003-1063-6. PMID 12748858. S2CID 41985805.
  12. ^ Chen NH, Reith ME, Quick MW (February 2004). "Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6". Pflügers Archiv. 447 (5): 519–531. doi:10.1007/s00424-003-1064-5. PMID 12719981. S2CID 34991320.
  13. ^ Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y (February 2004). "CATs and HATs: the SLC7 family of amino acid transporters" (PDF). Pflügers Archiv. 447 (5): 532–542. doi:10.1007/s00424-003-1086-z. PMID 14770310. S2CID 11670040.
  14. ^ Quednau BD, Nicoll DA, Philipson KD (February 2004). "The sodium/calcium exchanger family-SLC8". Pflügers Archiv. 447 (5): 543–548. doi:10.1007/s00424-003-1065-4. PMID 12734757. S2CID 26502273.
  15. ^ Orlowski J, Grinstein S (February 2004). "Diversity of the mammalian sodium/proton exchanger SLC9 gene family". Pflügers Archiv. 447 (5): 549–565. doi:10.1007/s00424-003-1110-3. PMID 12845533. S2CID 5691463.
  16. ^ Hagenbuch B, Dawson P (February 2004). "The sodium bile salt cotransport family SLC10" (PDF). Pflügers Archiv. 447 (5): 566–570. doi:10.1007/s00424-003-1130-z. PMID 12851823. S2CID 35115446.
  17. ^ Mackenzie B, Hediger MA (February 2004). "SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1". Pflügers Archiv. 447 (5): 571–579. doi:10.1007/s00424-003-1141-9. PMID 14530973. S2CID 7439663.
  18. ^ Hebert SC, Mount DB, Gamba G (February 2004). "Molecular physiology of cation-coupled Cl- cotransport: the SLC12 family". Pflügers Archiv. 447 (5): 580–593. doi:10.1007/s00424-003-1066-3. PMID 12739168. S2CID 21998913.
  19. ^ Markovich D, Murer H (February 2004). "The SLC13 gene family of sodium sulphate/carboxylate cotransporters". Pflügers Archiv. 447 (5): 594–602. doi:10.1007/s00424-003-1128-6. PMID 12915942. S2CID 7609066.
  20. ^ Shayakul C, Hediger MA (February 2004). "The SLC14 gene family of urea transporters". Pflügers Archiv. 447 (5): 603–609. doi:10.1007/s00424-003-1124-x. PMID 12856182. S2CID 21071284.
  21. ^ Daniel H, Kottra G (February 2004). "The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology". Pflügers Archiv. 447 (5): 610–618. doi:10.1007/s00424-003-1101-4. PMID 12905028. S2CID 22369521.
  22. ^ Halestrap AP, Meredith D (February 2004). "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv. 447 (5): 619–628. doi:10.1007/s00424-003-1067-2. PMID 12739169. S2CID 15498611.
  23. ^ Reimer RJ, Edwards RH (February 2004). "Organic anion transport is the primary function of the SLC17/type I phosphate transporter family". Pflügers Archiv. 447 (5): 629–635. doi:10.1007/s00424-003-1087-y. PMID 12811560. S2CID 9680597.
  24. ^ Eiden LE, Schäfer MK, Weihe E, Schütz B (February 2004). "The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine". Pflügers Archiv. 447 (5): 636–640. doi:10.1007/s00424-003-1100-5. PMID 12827358. S2CID 20764857.
  25. ^ Ganapathy V, Smith SB, Prasad PD (February 2004). "SLC19: the folate/thiamine transporter family". Pflügers Archiv. 447 (5): 641–646. doi:10.1007/s00424-003-1068-1. PMID 14770311. S2CID 7410075.
  26. ^ Collins JF, Bai L, Ghishan FK (February 2004). "The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors". Pflügers Archiv. 447 (5): 647–652. doi:10.1007/s00424-003-1088-x. PMID 12759754. S2CID 7737512.
  27. ^ Hagenbuch B, Meier PJ (February 2004). "Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties" (PDF). Pflügers Archiv. 447 (5): 653–665. doi:10.1007/s00424-003-1168-y. PMID 14579113. S2CID 21837213.
  28. ^ Koepsell H, Endou H (February 2004). "The SLC22 drug transporter family". Pflügers Archiv. 447 (5): 666–676. doi:10.1007/s00424-003-1089-9. PMID 12883891. S2CID 30419152.
  29. ^ Takanaga H, Mackenzie B, Hediger MA (February 2004). "Sodium-dependent ascorbic acid transporter family SLC23". Pflügers Archiv. 447 (5): 677–682. doi:10.1007/s00424-003-1104-1. PMID 12845532. S2CID 13018443.
  30. ^ Schnetkamp PP (February 2004). "The SLC24 Na+/Ca2+-K+ exchanger family: vision and beyond". Pflügers Archiv. 447 (5): 683–688. doi:10.1007/s00424-003-1069-0. PMID 14770312. S2CID 37553960.
  31. ^ Palmieri F (February 2004). "The mitochondrial transporter family (SLC25): physiological and pathological implications". Pflügers Archiv. 447 (5): 689–709. doi:10.1007/s00424-003-1099-7. PMID 14598172. S2CID 25304722.
  32. ^ Mount DB, Romero MF (February 2004). "The SLC26 gene family of multifunctional anion exchangers". Pflügers Archiv. 447 (5): 710–721. doi:10.1007/s00424-003-1090-3. PMID 12759755. S2CID 20302398.
  33. ^ Stahl A (February 2004). "A current review of fatty acid transport proteins (SLC27)". Pflügers Archiv. 447 (5): 722–727. doi:10.1007/s00424-003-1106-z. PMID 12856180. S2CID 2769738.
  34. ^ Gray JH, Owen RP, Giacomini KM (February 2004). "The concentrative nucleoside transporter family, SLC28". Pflügers Archiv. 447 (5): 728–734. doi:10.1007/s00424-003-1107-y. PMID 12856181. S2CID 24749954.
  35. ^ Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (February 2004). "The equilibrative nucleoside transporter family, SLC29". Pflügers Archiv. 447 (5): 735–743. doi:10.1007/s00424-003-1103-2. PMID 12838422. S2CID 8817821.
  36. ^ Palmiter RD, Huang L (February 2004). "Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers". Pflügers Archiv. 447 (5): 744–751. doi:10.1007/s00424-003-1070-7. PMID 12748859. S2CID 725350.
  37. ^ Petris MJ (February 2004). "The SLC31 (Ctr) copper transporter family". Pflügers Archiv. 447 (5): 752–755. doi:10.1007/s00424-003-1092-1. PMID 12827356. S2CID 23340930.
  38. ^ Gasnier B (February 2004). "The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids". Pflügers Archiv. 447 (5): 756–759. doi:10.1007/s00424-003-1091-2. PMID 12750892. S2CID 24669893.
  39. ^ Hirabayashi Y, Kanamori A, Nomura KH, Nomura K (February 2004). "The acetyl-CoA transporter family SLC33". Pflügers Archiv. 447 (5): 760–762. doi:10.1007/s00424-003-1071-6. PMID 12739170. S2CID 21247182.
  40. ^ Murer H, Forster I, Biber J (February 2004). "The sodium phosphate cotransporter family SLC34" (PDF). Pflügers Archiv. 447 (5): 763–767. doi:10.1007/s00424-003-1072-5. PMID 12750889. S2CID 34041192.
  41. ^ Ishida N, Kawakita M (February 2004). "Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35)". Pflügers Archiv. 447 (5): 768–775. doi:10.1007/s00424-003-1093-0. PMID 12759756. S2CID 8690030.
  42. ^ Boll M, Daniel H, Gasnier B (February 2004). "The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis". Pflügers Archiv. 447 (5): 776–779. doi:10.1007/s00424-003-1073-4. PMID 12748860. S2CID 25655241.
  43. ^ Bartoloni L, Antonarakis SE (February 2004). "The human sugar-phosphate/phosphate exchanger family SLC37". Pflügers Archiv. 447 (5): 780–783. doi:10.1007/s00424-003-1105-0. PMID 12811562. S2CID 24776306.
  44. ^ Mackenzie B, Erickson JD (February 2004). "Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family". Pflügers Archiv. 447 (5): 784–795. doi:10.1007/s00424-003-1117-9. PMID 12845534. S2CID 35457147.
  45. ^ Eide DJ (February 2004). "The SLC39 family of metal ion transporters". Pflügers Archiv. 447 (5): 796–800. doi:10.1007/s00424-003-1074-3. PMID 12748861. S2CID 11765308.
  46. ^ McKie AT, Barlow DJ (February 2004). "The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1)". Pflügers Archiv. 447 (5): 801–806. doi:10.1007/s00424-003-1102-3. PMID 12836025. S2CID 27340247.
  47. ^ Nakhoul NL, Hamm LL (February 2004). "Non-erythroid Rh glycoproteins: a putative new family of mammalian ammonium transporters". Pflügers Archiv. 447 (5): 807–812. doi:10.1007/s00424-003-1142-8. PMID 12920597. S2CID 24601165.
  48. ^ Boron WF (December 2010). "Sharpey-Schafer lecture: gas channels". Experimental Physiology. 95 (12): 1107–1130. doi:10.1113/expphysiol.2010.055244. PMC 3003898. PMID 20851859.
  49. ^ a b 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.
  50. ^ a b 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.
  51. ^ 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.
  52. ^ a b Perland E, Lekholm E, Eriksson MM, Bagchi S, Arapi V, Fredriksson R (2016). "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.
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  54. ^ 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.
  55. ^ 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.

SLC Tables. SLCtables

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