Symbol Xan_ur_permease Pfam clan CL0062 PROSITE PDOC00860 | Pfam PF00860 InterPro IPR006043 TCDB 2.A.40 | |
The Nucleobase:Cation Symporter-2 (NCS2) Family, also called the Nucleobase/Ascorbate Transporter (NAT) Family, consists of over 1000 sequenced proteins derived from gram-negative and gram-positive bacteria, archaea, fungi, plants and animals. The NCS2/NAT family is a member of the APC Superfamily of secondary carriers. Of the five known families of transporters that act on nucleobases, NCS2/NAT is the only one that is most widespread. Many functionally characterized members are specific for nucleobases including both purines and pyrimidines, but others are purine-specific. However, two closely related rat/human members of the family, SVCT1 and SVCT2, localized to different tissues of the body, co-transport L-ascorbate (vitamin C) and Na+ with a high degree of specificity and high affinity for the vitamin. Clustering of NCS2/NAT family members on the phylogenetic tree is complex, with bacterial proteins and eukaryotic proteins each falling into at least three distinct clusters. The plant and animal proteins cluster loosely together, but the fungal proteins branch from one of the three bacterial clusters forming a tighter grouping. E. coli possesses four distantly related paralogous members of the NCS2 family.
Contents
Structure
Proteins of the NCS2 family are 414–650 amino acyl residues in length and probably possess 14 TMSs. Lu et al. (2011) have concluded from x-ray crystallography that UraA (2.A.40.1.1) has 14 TMSs with two 7 TMS inverted repeats. A pair of antiparallel β-strands is located between TM3 and TM10 and has an important role in structural organization and substrate recognition. The structure is spatially arranged into a core domain and a gate domain. Uracil, located at the interface between the two domains, is coordinated mainly by residues from the core domain. Structural analyses and relationships to other structurally members of the APC superfamily suggest that alternating access of the substrate may be achieved through conformational changes of the gate domain.
Crystal structures
Uracil permease, UraA UraA with bound uracil at 2.8Å resolution PDB: 3QE7.
Transport reaction
The generalized transport reactions catalyzed by proteins of the NAT/NCS2 family are:
Nucleobase (out) H+ (out) → Nucleobase (in) H+ (in). Ascorbate (out) Na+ (out) → Ascorbate (in) Na+ (in).Characterized proteins
Several proteins make up the NCS2/NAT family. A full list of these proteins can be found in the Transporter Classification Database. A few types of proteins that make up the NCS2/NAT family include: