Atypical SLCs

Atypical SLCs are novel plausible secondary active or facilitative transporter proteins that share ancestral background with the known solute carriers. However, they have not been assigned a name according to the SLC root system, or been classified into any of the existing SLC families.[1][2]

Atypical major facilitator superfamily] transport families

Most atypical SLCs are families within the major facilitator superfamily (MFS).[3] These atypical SLCs are plausible secondary active or facilitative transporter proteins that share ancestry with the known solute carriers.[1][2][4] They are, however, not named according to the SLC root system, or classified into any of the existing SLC families.[1] ATMFs are categorised based on their sequence similarity and phylogenetic closeness.[3]

AMTF Family members SLC family
AMTF1 MFSD9, MFSD10, MFSD14A, MFSD14B SLC46
AMTF2 MFSD8
AMTF3 MFSD4A, MFSD4B
AMTF4 CLN3
AMTF5 MFSD7 SLC49
AMTF6 MFSD1, MFSD5
AMTF7 MFSD12
AMTF8 MFSD2A, MFSD2B
AMTF9 SV2A, SV2B, SV2C, SVOP, SVOPL SLC22
AMTF10 MFSD11, UNC93A, UNC93B1
AMTF11 SPNS1, SPNS2, SPNS3
AMTF12 MFSD13A
AMTF13 MFSD6
AMTF14 MFSD6L
AMTF15 MFSD3

Some Atypical SLC of MFS type are: OCA2, CLN3, SPNS1, SPNS2, SPNS3, SV2A, SV2B, SV2C, SVOP, SVOPL, MFSD1, MFSD2A, MFSD2B, MFSD3, MFSD4A,[5] MFSD4B, MFSD5, MFSD6, MFSD6L, MFSD8, MFSD9,[5] MFSD10, MFSD11, MFSD12, MFSD13A, MFSD14A, MFSD14B, UNC93A[6] and UNC93B1. All these are atypical SLCs found within the Major facilitator superfamily. Also TMEM104 (APC clan), OCA2 (IT clan) and CLN3 (having no clan) are atypical SLCs in humans.

Non-MFS transport families

Although most atypical SLCs are from the major facilitator superfamily, there are exceptions: TMEM104 (APC superfamily), OCA2 (IT superfamily) and CLN3 (unknown superfamily).[1]

References
  1. Perland, Emelie; Fredriksson, Robert (March 2017). "Classification Systems of Secondary Active Transporters". Trends in Pharmacological Sciences. 38 (3): 305–315. doi:10.1016/j.tips.2016.11.008. ISSN 1873-3735. PMID 27939446.
  2. Sreedharan, Smitha; Stephansson, Olga; Schiöth, Helgi B.; Fredriksson, Robert (2011-06-01). "Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters". Gene. 478 (1–2): 11–18. doi:10.1016/j.gene.2010.10.011. ISSN 1879-0038. PMID 21044875.
  3. Perland, Emelie; Bagchi, Sonchita; Klaesson, Axel; Fredriksson, Robert (2017-09-01). "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. ISSN 2046-2441. PMC 5627054. PMID 28878041.
  4. Höglund, Pär J.; Nordström, Karl J. V.; Schiöth, Helgi B.; Fredriksson, Robert (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. ISSN 1537-1719. PMC 3058773. PMID 21186191.
  5. Perland, Emelie; Hellsten, Sofie Victoria; Schweizer, Nadine; Arapi, Vasiliki; Rezayee, Fatemah; Bushra, Mona; Fredriksson, Robert (2017). "Structural prediction of two novel human atypical SLC transporters, MFSD4A and MFSD9, and their neuroanatomical distribution in mice". PLoS ONE. 12 (10): e0186325. doi:10.1371/journal.pone.0186325. ISSN 1932-6203. PMC 5648162. PMID 29049335.
  6. Ceder, Mikaela M.; Lekholm, Emilia; Hellsten, Sofie V.; Perland, Emelie; Fredriksson, Robert (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. ISSN 1662-5099. PMC 5671512. PMID 29163028.


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