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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]
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. [7] [8] [9]
Although most atypical SLCs are from the major facilitator superfamily, there are exceptions: TMEM104 (APC superfamily), OCA2 (IT superfamily) and CLN3 (unknown superfamily). [1]
Battenin is a protein that in humans is encoded by the CLN3 gene located on chromosome 16. Battenin is not clustered into any Pfam clan, but it is included in the TCDB suggesting that it is a transporter. In humans, it belongs to the atypical SLCs due to its structural and phylogenetic similarity to other SLC transporters.
The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. 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.
The major facilitator superfamily (MFS) is a superfamily of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients.
Major facilitator superfamily domain-containing protein 2 -- also known as sodium-dependent lysophosphatidylcholine symporter 1 -- is a protein that in humans is encoded by the MFSD2A gene. MFSD2A is a membrane transport protein that is expressed in the endothelium of the blood–brain barrier (BBB) and has an essential role in BBB formation and function. Genetic ablation of MFSD2A results in leaky BBB and increases central nervous system endothelial cell vesicular transcytosis without otherwise affecting tight junctions. MFSD2A is an atypical SLC, thus a predicted SLC transporter. It clusters phylogenetically to AMTF8.
Major facilitator superfamily domain containing 8 also called MFSD8 is a protein that in humans is encoded by the MFSD8 gene. MFSD8 is an atypical SLC, thus a predicted SLC transporter. It clusters phylogenetically to the Atypical MFS Transporter family 2 (AMTF2).
Transmembrane protein 241 is a ubiquitous sugar transporter protein which in humans is encoded by the TMEM241 gene.
Unc-93 homolog A is a protein that in humans is encoded by the UNC93A gene.
Major facilitator superfamily domain containing 7 is a protein that in humans is encoded by the MFSD7 gene.
The amino acid-polyamine-organocation (APC) superfamily is the second largest superfamily of secondary carrier proteins currently known, and it contains several Solute carriers. Originally, the APC superfamily consisted of subfamilies under the transporter classification number. This superfamily has since been expanded to include eighteen different families.
Transmembrane protein 268 is a protein that in humans is encoded by TMEM268 gene. The protein is a transmembrane protein of 342 amino acids long with eight alternative splice variants. The protein has been identified in organisms from the common fruit fly to primates. To date, there has been no protein expression found in organisms simpler than insects.
Major facilitator superfamily domain containing 14A is a protein that in humans is encoded by the MFSD14A gene. MFSD14A is an atypical solute carrier of MFS type. HGNC:23363
Major facilitator superfamily domain containing 1 is a protein belonging to the MFS Pfam clan. It is an Atypical solute carrier.
Major facilitator superfamily domain containing 3 (MFSD3) is a protein belonging to the MFS Pfam clan. It is an Atypical solute carrier located to the neuronal plasma membrane.
Major facilitator superfamily domain containing 5 is an atypical SLC expressed in neuronal plasma membrane. It is a plausible Solute carrier transporter. It transports molybdate anions, and it interacts with GLP-1R.
Major facilitator superfamily domain containing 14B is an atypical solute carrier of MFS type. It locates to intracellular membranes.
Major facilitator superfamily domain-containing protein 9 is a protein that in humans is encoded by the MFSD9 gene. It is a potential solute carrier, and called atypical solute carrier since it is not named according to the SLC nomenclature. It is expressed both in central and peripheral organs.
Major facilitator superfamily domain containing 4A is a protein belonging to the MFS Pfam clan. It is an Atypical solute carrier, thus a plausible SLC transporter in humans. MFSD4A has been identified in both central and peripheral areas.
Zinc transporter ZIP8 is a cation/bicarbonate symporter protein which in humans is encoded by the SLC39A8 gene.
TMEM128, also known as Transmembrane Protein 128, is a protein that in humans is encoded by the TMEM128 gene. TMEM128 has three variants, varying in 5' UTR's and start codon location. TMEM128 contains four transmembrane domains and is localized in the Endoplasmic Reticulum membrane. TMEM128 contains a variety of regulation at the gene, transcript, and protein level. While the function of TMEM128 is poorly understood, it interacts with several proteins associated with the cell cycle, signal transduction, and memory.
Major facilitator superfamily domain containing 6 like (MFSD6L) is a protein encoded by the MFSD6L gene in humans. The MFSD6L protein is a transmembrane protein that is part of the major facilitator superfamily (MFS) that uses chemiosmotic gradients to facilitate the transport of small solutes across cell membranes.
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