Solute carrier family

The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 65 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:

  • SLCnXm

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 (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[4]

Putative SLCs

Putative SLCs, also called atypical SLCs, are novel, plausible secondary active or facilitative transansporter proteins that share ancestral background with the known SLCs. However, they have not been assigned a name according to the SLC root system, or been classified into any of the existing SLC families.[2][47] The atypical SLCs of MFS type can, however, be subdivided into 15 Putative MFS Transporter Families (AMTF).[47]

All the putative SLCs are plausible SLC transporters. They are only "atypical" when it comes to their names; the genes are not called according to the SLC root system.

Here are some Putative SLCs listed: OCA2, CLN3, TMEM104, SPNS1, SPNS2, SPNS3, SV2A, SV2B, SV2C, SVOP, SVOPL, MFSD1,[48] MFSD2A, MFSD2B, MFSD3,[48] MFSD4A,[49] MFSD4B, MFSD5,[50] MFSD6, MFSD6L, MFSD8, MFSD9,[49] MFSD10, MFSD11,[50] MFSD12, MFSD13A, MFSD14A,[51] MFSD14B,[51] UNC93A[52] and UNC93B1.

gollark: Fine, an insu-pen.
gollark: ddg! epi-pen (mathematics)
gollark: Yes.
gollark: Hmm. That sounds annoying.
gollark: Testosterone in the water cooler/food supply?

References
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  2. 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.
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  4. "SLCtables". slc.bioparadigms.org. Retrieved 2018-03-07.
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  22. 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): 636–40. doi:10.1007/s00424-003-1100-5. PMID 12827358.
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  28. Schnetkamp PP (February 2004). "The SLC24 Na+/Ca2+-K+ exchanger family: vision and beyond". Pflügers Archiv. 447 (5): 683–8. doi:10.1007/s00424-003-1069-0. PMID 14770312.
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  31. Stahl A (February 2004). "A current review of fatty acid transport proteins (SLC27)". Pflügers Archiv. 447 (5): 722–7. doi:10.1007/s00424-003-1106-z. PMID 12856180.
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SLC Tables. SLCtables

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