| TCID | Name | Domain | Kingdom/Phylum | Protein(s) |
|---|---|---|---|---|
|
2.A.48.1.1 | Folate/folate derivative transporter, RFC1. Although oligomeric, each monomer provides the channel (Hou et al., 2010). It is downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain, causing malabsorption (Bukhari et al., 2011). 5-Aminoimidazole-4-carboxamide riboside (AICAR), an agent with diverse pharmacological properties, augments transport of folates and antifolates by promoting substrate:substrate antiport (Visentin et al. 2012). Its role in antifolate cancer chemotherapy has been reviewed (Matherly et al. 2014). In cats, this protein is the receptor for feline leukemia virus (feLV) (Miyake et al. 2019). The R27H polymorphism affects the secondary and tertiary structures of SLC19A1 with a loss of ligand-binding sites (Naushad et al. 2019). 2'3'-cyclic-GMP-AMP (cGAMP), a second messenger that activates the antiviral stimulator of IFN genes (STING), elicits an antitumoral immune response. SLC19A1 is an importer that transports extracellular cGAMP into the cytosol (Li et al. 2022), and binding of cyclic dinucleotides has been demonstrated (Zhang et al. 2022). Folate supplementation has been reviewed (He and Li 2023). FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of methotraxate (MTX), whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells (Bai et al. 2024). Import of extracellular 2'-3'cGAMP occurs via the folate transporter, SLC19A1, and this establishes an antiviral response that limits herpes simplex virus-1 (Szemere and Murphy 2024).
| Eukaryota |
Metazoa, Chordata | SLC19A1 of Homo sapiens |
|
2.A.48.1.2 | Thiamine uptake transporter-1, THTR-1, the thiamine-responsive megaloblastic anemia (TRMA) protein (Manimaran et al. 2016). Downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain causing malabsorption (Bukhari et al., 2011). | Eukaryota |
Metazoa, Chordata | SLC19A2 of Homo sapiens |
|
2.A.48.1.3 | The folate transporter, FolT-1 of 453 aas, with a Km for folate of 1.2μM and a Ki for Sulfasalazine of 0.1 mM. Folt-1 also transports reduced folate and substituted folate derivatives. The system is maximally expressed in the pharynx and intestine, and it is developmentallyl regulated. DIDS, a general anion inhibitor, also inhibits (Balamurugan et al., 2007). FOLT-1 function affects both the soma and the germline. folt-1(ok1460) hermaphrodites suffer severely diminished lifespan and germline defects that result in sterility. Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and nematodes (Austin et al. 2010). | Eukaryota |
Metazoa, Nematoda | FolT-1 of Caenorhabditis elegans (Q17766) |
|
2.A.48.1.4 | Thiamine (and biotin) transporter-2, ThTr-2, of 496 aas and 12 TMSs. Downregulated in Chronic Kidney Disease (CKD) in heart, liver, and brain causing malabsorption (Bukhari et al., 2011). Activated by microtubules but not microfilaments (Subramanian et al. 2013). Activated by direct interaction with the 4 TMS protein, TM4 of the L6 family, member 4, TM4SF4 (P48230) (Subramanian et al. 2014). Mutations result in thiamine metabolism dysfunction syndrome 2, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD). This neurometabolic disease typically presents in early childhood with progressive neurodegeneration, including confusion, seizures, and dysphagia, advancing to coma and death (Whitford et al. 2017). | Eukaryota |
Metazoa, Chordata | SLC19A3, Thiamine transporter-2 of Homo sapiens |
|
2.A.48.1.5 | Slime mold RFC homologue | Eukaryota |
Evosea | RFC homologue of Dictyostelium discoideum (Q559K0) |
|
2.A.48.1.6 | Giardia RFC homologue | Eukaryota |
Fornicata | RFC homologue of Giardia lamblia (A8BIM9) |
|
2.A.48.1.7 | Folate transporter, Folt-2 of 424 aas and 12 TMSs in an apparent 5 + 5 or 6 + 6 TMS arrangement, probably the latter. | Eukaryota |
Metazoa, Nematoda | Folt2 of Caenorhabditis elegans |