2.A.40 The Nucleobase:Cation Symporter-2 (NCS2) Family
The NCS2 family, also called the nucleobase/ascorbate transporter (NAT) family (Karatza et al., 2006), consists of over 100 currently sequenced proteins derived from Gram-negative and Gram-positive bacteria, archaea, fungi, plants and animals. Most functionally characterized members are specific for nucleobases including both purines and pyrimidines. However, two closely related rat members of the family, SVCT1 and SVCT2, localized to different tissues of the body, cotransport L-ascorbate and Na+ with a high degree of specificity and high affinity for the vitamin. Clustering of NCS2 family members on the phylogenetic tree is complex with bacterial proteins and eukaryotic proteins each falling into three distinct clusters. The plant and animal proteins cluster loosely together, but the fungal proteins branch from one of the three bacterial clusters. E. coli possesses four distantly related paralogous members of the NCS2 family. The NCS2 family appears to be distantly related to the NCS1 family (TC #2.A.39). An alternative designation for the NCS2 family is the Nucleobase-Ascorbate Transporter (NAT) family.
Proteins of the NCS2 family are 414-650 amino acyl residues in length and probably possess twelve transmembrane α-helical spanners (TMSs). The generalized transport reactions catalyzed by proteins of the NCS2 are:
Nucleobase (out) + H+(out) → Nucleobase (in) + H+(in).
Ascorbate (out) + Na+(out) → Ascorbate (in) + Na+(in).
