Biology:Solute carrier family

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Short description: Family of membrane transport proteins

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

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:

  • facilitative transporters (allow solutes to flow downhill with their electrochemical gradients)
  • secondary active transporters (allow solutes to flow uphill against their electrochemical gradient by coupling to transport of a second solute that flows downhill with its gradient such that the overall free energy change is still favorable)

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

  • primary active transporters (allow flow uphill against electrochemical gradients) such as ABC (ATP Binding Cassette) transporters by coupling transport to an energy releasing event such as ATP hydrolysis
  • ion channels
  • aquaporins (water channels)

Subcellular distribution

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

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

[math]\ce{ SLCnXm }[/math]

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

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]
    • (SLC8A1, SLC8A2, SLC8A3)
  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]
    • (SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14)
  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]
    • (SLC28A1, SLC28A2, SLC28A3)
  29. facilitative nucleoside transporter[35]
    • (SLC29A1, SLC29A2, SLC29A3, SLC29A4)
  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]
    • subfamily A (SLC35A1, SLC35A2, SLC35A3, SLC35A4, SLC35A5)
    • subfamily B (SLC35B1, SLC35B2, SLC35B3, SLC35B4)
    • subfamily C (SLC35C1, SLC35C2)
    • subfamily D (SLC35D1, SLC35D2, SLC35D3)
    • subfamily E (SLC35E1, SLC35E2A, SLC35E2B, SLC35E3, SLC35E4)
    • subfamily F (SLC35F1, SLC35F2, SLC35F3, SLC35F4, SLC35F5)
    • subfamily G (SLC35G1, SLC35G3, SLC35G4, SLC35G5, SLC35G6)
  36. proton-coupled amino acid transporter[42]
    • (SLC36A1, SLC36A2, SLC36A3, SLC36A4)
  37. sugar-phosphate/phosphate exchanger[43]
    • (SLC37A1, SLC37A2, SLC37A3, SLC37A4)
  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
    • (SLC51A, SLC51B)
  52. Riboflavin transporter family RFVT/SLC52
    • (SLC52A1, SLC52A2, SLC52A3)
  53. Phosphate carriers
    • (XPR1(SLC53A1)
  54. Mitochondrial pyruvate carriers
    • (MPC1(SLC54A1), MPC2(SLC54A2), MPC1L(SLC54A3))
  55. Mitochondrial cation/proton exchangers
    • (LETM1(SLC55A1), LETM2(SLC55A2), LETMD1(SLC55A3))
  56. Sideroflexins
    • (SFXN1(SLC56A1), SFXN2(SLC56A2), SFXN3(SLC56A3), SFXN4(SLC56A4), SFXN5(SLC56A5))
  57. NiPA-like magnesium transporter family
  58. MagT-like magnesium transporter family
    • (MAGT1(SLC58A1), TUSC3(SLC58A2))
  59. Sodium-dependent lysophosphatidylcholine symporter family
    • (MFSD2A(SLC59A1), MFSD2B(SLC59A2))
  60. Glucose transporters
    • (MFSD4A(SLC60A1), MFSD4B(SLC60A2))
  61. Molybdate transporter family
  62. Pyrophosphate transporters
    • (ANKH(SLC62A1))
  63. Sphingosine-phosphate transporters
    • (SPNS1(SLC63A1), SPNS2(SLC63A2), SPNS3(SLC63A3))
  64. Golgi Ca2+/H+ exchangers
  65. NPC-type cholesterol transporters
  66. Cationic amino acid exporters

Putative SLCs

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

  1. ↑ "The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction". Pflügers Archiv 447 (5): 465–468. February 2004. doi:10.1007/s00424-003-1192-y. PMID 14624363. 
  2. ↑ 2.0 2.1 "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. 
  3. ↑ "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. April 2011. doi:10.1093/molbev/msq350. PMID 21186191. 
  4. ↑ "The ABCs of membrane transporters in health and disease (SLC series): introduction". Molecular Aspects of Medicine 34 (2–3): 95–107. 2013. doi:10.1016/j.mam.2012.12.009. PMID 23506860. 
  5. ↑ "Analysis and update of the human solute carrier (SLC) gene superfamily". Human Genomics 3 (2): 195–206. January 2009. doi:10.1186/1479-7364-3-2-195. PMID 19164095. 
  6. ↑ "SLCtables". http://slc.bioparadigms.org/. 
  7. ↑ "The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects". Pflügers Archiv 447 (5): 469–479. February 2004. doi:10.1007/s00424-003-1146-4. PMID 14530974. 
  8. ↑ "The SLC2 family of facilitated hexose and polyol transporters". Pflügers Archiv 447 (5): 480–489. February 2004. doi:10.1007/s00424-003-1085-0. PMID 12750891. https://serval.unil.ch/notice/serval:BIB_72AB04FFF9E9. 
  9. ↑ "The ancillary proteins of HATs: SLC3 family of amino acid transporters". Pflügers Archiv 447 (5): 490–494. February 2004. doi:10.1007/s00424-003-1062-7. PMID 14770309. 
  10. ↑ "The SLC4 family of HCO 3 - transporters". Pflügers Archiv 447 (5): 495–509. February 2004. doi:10.1007/s00424-003-1180-2. PMID 14722772. 
  11. ↑ "The sodium/glucose cotransport family SLC5". Pflügers Archiv 447 (5): 510–518. February 2004. doi:10.1007/s00424-003-1063-6. PMID 12748858. 
  12. ↑ "Synaptic uptake and beyond: the sodium- and chloride-dependent neurotransmitter transporter family SLC6". Pflügers Archiv 447 (5): 519–531. February 2004. doi:10.1007/s00424-003-1064-5. PMID 12719981. 
  13. ↑ "CATs and HATs: the SLC7 family of amino acid transporters". Pflügers Archiv 447 (5): 532–542. February 2004. doi:10.1007/s00424-003-1086-z. PMID 14770310. https://www.zora.uzh.ch/id/eprint/156045/1/ZORA_NL_156045.pdf. 
  14. ↑ "The sodium/calcium exchanger family-SLC8". Pflügers Archiv 447 (5): 543–548. February 2004. doi:10.1007/s00424-003-1065-4. PMID 12734757. 
  15. ↑ "Diversity of the mammalian sodium/proton exchanger SLC9 gene family". Pflügers Archiv 447 (5): 549–565. February 2004. doi:10.1007/s00424-003-1110-3. PMID 12845533. https://escholarship.mcgill.ca/concern/articles/8623j430m. 
  16. ↑ "The sodium bile salt cotransport family SLC10". Pflügers Archiv 447 (5): 566–570. February 2004. doi:10.1007/s00424-003-1130-z. PMID 12851823. https://www.zora.uzh.ch/id/eprint/155787/1/ZORA_NL_155787.pdf. 
  17. ↑ "SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1". Pflügers Archiv 447 (5): 571–579. February 2004. doi:10.1007/s00424-003-1141-9. PMID 14530973. 
  18. ↑ "Molecular physiology of cation-coupled Cl- cotransport: the SLC12 family". Pflügers Archiv 447 (5): 580–593. February 2004. doi:10.1007/s00424-003-1066-3. PMID 12739168. 
  19. ↑ "The SLC13 gene family of sodium sulphate/carboxylate cotransporters". Pflügers Archiv 447 (5): 594–602. February 2004. doi:10.1007/s00424-003-1128-6. PMID 12915942. 
  20. ↑ "The SLC14 gene family of urea transporters". Pflügers Archiv 447 (5): 603–609. February 2004. doi:10.1007/s00424-003-1124-x. PMID 12856182. 
  21. ↑ "The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology". Pflügers Archiv 447 (5): 610–618. February 2004. doi:10.1007/s00424-003-1101-4. PMID 12905028. 
  22. ↑ "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv 447 (5): 619–628. February 2004. doi:10.1007/s00424-003-1067-2. PMID 12739169. 
  23. ↑ "Organic anion transport is the primary function of the SLC17/type I phosphate transporter family". Pflügers Archiv 447 (5): 629–635. February 2004. doi:10.1007/s00424-003-1087-y. PMID 12811560. 
  24. ↑ "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. February 2004. doi:10.1007/s00424-003-1100-5. PMID 12827358. 
  25. ↑ "SLC19: the folate/thiamine transporter family". Pflügers Archiv 447 (5): 641–646. February 2004. doi:10.1007/s00424-003-1068-1. PMID 14770311. 
  26. ↑ "The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors". Pflügers Archiv 447 (5): 647–652. February 2004. doi:10.1007/s00424-003-1088-x. PMID 12759754. 
  27. ↑ "Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties". Pflügers Archiv 447 (5): 653–665. February 2004. doi:10.1007/s00424-003-1168-y. PMID 14579113. https://www.zora.uzh.ch/id/eprint/156363/1/ZORA_NL_156363.pdf. 
  28. ↑ "The SLC22 drug transporter family". Pflügers Archiv 447 (5): 666–676. February 2004. doi:10.1007/s00424-003-1089-9. PMID 12883891. 
  29. ↑ "Sodium-dependent ascorbic acid transporter family SLC23". Pflügers Archiv 447 (5): 677–682. February 2004. doi:10.1007/s00424-003-1104-1. PMID 12845532. 
  30. ↑ "The SLC24 Na+/Ca2+-K+ exchanger family: vision and beyond". Pflügers Archiv 447 (5): 683–688. February 2004. doi:10.1007/s00424-003-1069-0. PMID 14770312. 
  31. ↑ "The mitochondrial transporter family (SLC25): physiological and pathological implications". Pflügers Archiv 447 (5): 689–709. February 2004. doi:10.1007/s00424-003-1099-7. PMID 14598172. 
  32. ↑ "The SLC26 gene family of multifunctional anion exchangers". Pflügers Archiv 447 (5): 710–721. February 2004. doi:10.1007/s00424-003-1090-3. PMID 12759755. 
  33. ↑ "A current review of fatty acid transport proteins (SLC27)". Pflügers Archiv 447 (5): 722–727. February 2004. doi:10.1007/s00424-003-1106-z. PMID 12856180. 
  34. ↑ "The concentrative nucleoside transporter family, SLC28". Pflügers Archiv 447 (5): 728–734. February 2004. doi:10.1007/s00424-003-1107-y. PMID 12856181. 
  35. ↑ "The equilibrative nucleoside transporter family, SLC29". Pflügers Archiv 447 (5): 735–743. February 2004. doi:10.1007/s00424-003-1103-2. PMID 12838422. 
  36. ↑ "Efflux and compartmentalization of zinc by members of the SLC30 family of solute carriers". Pflügers Archiv 447 (5): 744–751. February 2004. doi:10.1007/s00424-003-1070-7. PMID 12748859. 
  37. ↑ "The SLC31 (Ctr) copper transporter family". Pflügers Archiv 447 (5): 752–755. February 2004. doi:10.1007/s00424-003-1092-1. PMID 12827356. 
  38. ↑ "The SLC32 transporter, a key protein for the synaptic release of inhibitory amino acids". Pflügers Archiv 447 (5): 756–759. February 2004. doi:10.1007/s00424-003-1091-2. PMID 12750892. 
  39. ↑ "The acetyl-CoA transporter family SLC33". Pflügers Archiv 447 (5): 760–762. February 2004. doi:10.1007/s00424-003-1071-6. PMID 12739170. 
  40. ↑ "The sodium phosphate cotransporter family SLC34". Pflügers Archiv 447 (5): 763–767. February 2004. doi:10.1007/s00424-003-1072-5. PMID 12750889. https://www.zora.uzh.ch/id/eprint/1384/1/ZORA_NL_1384.pdf. 
  41. ↑ "Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35)". Pflügers Archiv 447 (5): 768–775. February 2004. doi:10.1007/s00424-003-1093-0. PMID 12759756. 
  42. ↑ "The SLC36 family: proton-coupled transporters for the absorption of selected amino acids from extracellular and intracellular proteolysis". Pflügers Archiv 447 (5): 776–779. February 2004. doi:10.1007/s00424-003-1073-4. PMID 12748860. 
  43. ↑ "The human sugar-phosphate/phosphate exchanger family SLC37". Pflügers Archiv 447 (5): 780–783. February 2004. doi:10.1007/s00424-003-1105-0. PMID 12811562. 
  44. ↑ "Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family". Pflügers Archiv 447 (5): 784–795. February 2004. doi:10.1007/s00424-003-1117-9. PMID 12845534. 
  45. ↑ "The SLC39 family of metal ion transporters". Pflügers Archiv 447 (5): 796–800. February 2004. doi:10.1007/s00424-003-1074-3. PMID 12748861. 
  46. ↑ "The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1)". Pflügers Archiv 447 (5): 801–806. February 2004. doi:10.1007/s00424-003-1102-3. PMID 12836025. 
  47. ↑ "Non-erythroid Rh glycoproteins: a putative new family of mammalian ammonium transporters". Pflügers Archiv 447 (5): 807–812. February 2004. doi:10.1007/s00424-003-1142-8. PMID 12920597. 
  48. ↑ "Sharpey-Schafer lecture: gas channels". Experimental Physiology 95 (12): 1107–1130. December 2010. doi:10.1113/expphysiol.2010.055244. PMID 20851859. 
  49. ↑ 49.0 49.1 "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. 
  50. ↑ 50.0 50.1 "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. 
  51. ↑ 51.0 51.1 "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. 
  52. ↑ 52.0 52.1 "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. doi:10.1371/journal.pone.0156912. PMID 27272503. Bibcode: 2016PLoSO..1156912P. 
  53. ↑ 53.0 53.1 "Putative Membrane-Bound Transporters MFSD14A and MFSD14B Are Neuronal and Affected by Nutrient Availability". Frontiers in Molecular Neuroscience 10: 11. 2017. doi:10.3389/fnmol.2017.00011. PMID 28179877. 
  54. ↑ "The Neuronal and Peripheral Expressed Membrane-Bound UNC93A Respond to Nutrient Availability in Mice" (in English). Frontiers in Molecular Neuroscience 10: 351. 2017. doi:10.3389/fnmol.2017.00351. PMID 29163028. 
  55. ↑ "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" (in English). Frontiers in Cell and Developmental Biology 8: 580291. 2020. doi:10.3389/fcell.2020.580291. PMID 33163493. 

SLC Tables. SLCtables

External links



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