Atypical SLCs explained

Atypical Solute Carrier Families (Atypical SLCs) are novel plausible secondary active or facilitative transporter proteins that share ancestral background with the known solute carrier families (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.^{[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. ATMFs are categorised based on their sequence similarity and phylogenetic closeness.

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, 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. ^{[7] [8] [9]}

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]

Notes and References

1. Perland E, Fredriksson R . Classification Systems of Secondary Active Transporters . Trends in Pharmacological Sciences . 38 . 3 . 305–315 . March 2017 . 27939446 . 10.1016/j.tips.2016.11.008 .
2. Sreedharan S, Stephansson O, Schiöth HB, Fredriksson R . Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters . Gene . 478 . 1–2 . 11–18 . June 2011 . 21044875 . 10.1016/j.gene.2010.10.011 .
3. Perland E, Bagchi S, Klaesson A, Fredriksson R . 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 . 28878041 . 5627054 . 10.1098/rsob.170142 .
4. Höglund PJ, Nordström KJ, Schiöth HB, Fredriksson R . 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 . 21186191 . 3058773 . 10.1093/molbev/msq350 .
5. Perland E, Hellsten SV, Schweizer N, Arapi V, Rezayee F, Bushra M, Fredriksson R . Structural prediction of two novel human atypical SLC transporters, MFSD4A and MFSD9, and their neuroanatomical distribution in mice . PLOS ONE . 12 . 10 . e0186325 . 2017 . 29049335 . 5648162 . 10.1371/journal.pone.0186325 . free . 2017PLoSO..1286325P .
6. Ceder MM, Lekholm E, Hellsten SV, Perland E, Fredriksson R . The Neuronal and Peripheral Expressed Membrane-Bound UNC93A Respond to Nutrient Availability in Mice . English . Frontiers in Molecular Neuroscience . 10 . 351 . 2017 . 29163028 . 5671512 . 10.3389/fnmol.2017.00351 . free .
7. Web site: TMEM104 transmembrane protein 104 [Homo sapiens (human)] - Gene - NCBI ]. 2022-03-14 . www.ncbi.nlm.nih.gov.
8. Web site: OCA2 OCA2 melanosomal transmembrane protein [Homo sapiens (human)] - Gene - NCBI ]. 2022-03-14 . www.ncbi.nlm.nih.gov.
9. Web site: CLN3 CLN3 lysosomal/endosomal transmembrane protein, battenin [Homo sapiens (human)] - Gene - NCBI ]. 2022-03-14 . www.ncbi.nlm.nih.gov.