NCS1s are essential components of salvage pathways for nucleobases and related metabolites; their known substrates include allantoin, uracil, thiamine, and nicotinamide riboside. This family includes Microbacterium liquefaciens Mhp1, a transporter that mediates the uptake of indolyl methyl- and benzyl-hydantoins as part of a metabolic salvage pathway for their conversion to amino acids. It also includes various Saccharomyces cerevisiae transporters: Fcy21p (Purine-cytosine permease), vitamin B6 transporter Tpn1, nicotinamide riboside transporter 1 (Nrt1p, also called Thi71p), Dal4p (allantoin permease), Fui1p (uridine permease), and Fur4p (uracil permease). Mhp1 has 12 transmembrane (TM) helices (an inverted topology repeat: TMs1-5 and TMs6-10, and TMs11-12; TMs numbered to conform to the solute carrier 6 family Aquifex aeolicus LeuT). NCS1s belong to a superfamily which also contains the solute carrier 5 family sodium/glucose transporters (SLC5s), and SLC6 neurotransmitter transporters.
Comment:based on the structures of Vibrio parahaemolyticus vSGLT (SLC5), Aquifex aeolicus LeuT (SLC6), and the NCS1, Microbacterium liquefaciens Mhp1, bound with Na+, functional studies of Escherichia coli PutP (SLC5) and mammalian NIS (SLC5), and mutational analysis of vSGLT
Comment:one of two Na+ binding sites in Aquifex aeolicus LeuT, where it is referred to as the Na binding site 2
Jiyao W et al.(2023). "The conserved domain database in 2023.",