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:

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

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]

where:

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]
  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]
    • 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]
  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
    • (MPC1(SLC54A1), MPC2(SLC54A2), MPC1L(SLC54A3))
  55. Mitochondrial cation/proton exchangers
  56. Sideroflexins
    • (SFXN1(SLC56A1), SFXN2(SLC56A2), SFXN3(SLC56A3), SFXN4(SLC56A4), SFXN5(SLC56A5))
  57. NiPA-like magnesium transporter family
  58. MagT-like magnesium transporter family
  59. Sodium-dependent lysophosphatidylcholine symporter family
    • (MFSD2A(SLC59A1), MFSD2B(SLC59A2))
  60. Glucose transporters
    • (MFSD4A(SLC60A1), MFSD4B(SLC60A2))
  61. Molybdate transporter family
  62. Pyrophosphate transporters
  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

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SLC Tables. SLCtables

External links

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)
Genetic disorder, membrane: Solute carrier disorders
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