Nucleobase cation symporter-2

The Nucleobase cation symporter-2 (NCS2) family, also called the Nucleobase ascorbate transporter (NAT) family,[1] 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.[2] Of the five known families of transporters that act on nucleobases, NCS2/NAT is the only one that is most widespread.[3] 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.[4] 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.[5] E. coli possesses four distantly related paralogous members of the NCS2 family.[6]

Xanthine/uracil/vitamin C permease
Identifiers
SymbolXan_ur_permease
PfamPF00860
Pfam clanCL0062
InterProIPR006043
PROSITEPDOC00860
TCDB2.A.40
OPM superfamily64
OPM protein3qe7

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.[7] Uracil is located at the interface between the two domains.[2]

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:[6]

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:[6]

References
  1. Karatza P, Panos P, Georgopoulou E, Frillingos S (Dec 2006). "Cysteine-scanning analysis of the nucleobase-ascorbate transporter signature motif in YgfO permease of Escherichia coli: Gln-324 and Asn-325 are essential, and Ile-329-Val-339 form an alpha-helix". The Journal of Biological Chemistry. 281 (52): 39881–90. doi:10.1074/jbc.M605748200. PMID 17077086.
  2. Wong FH, Chen JS, Reddy V, Day JL, Shlykov MA, Wakabayashi ST, Saier MH (2012-01-01). "The amino acid-polyamine-organocation superfamily". Journal of Molecular Microbiology and Biotechnology. 22 (2): 105–13. doi:10.1159/000338542. PMID 22627175.
  3. Frillingos S (2012-01-01). "Insights to the evolution of Nucleobase-Ascorbate Transporters (NAT/NCS2 family) from the Cys-scanning analysis of xanthine permease XanQ". International Journal of Biochemistry and Molecular Biology. 3 (3): 250–72. PMC 3476789. PMID 23097742.
  4. Diallinas G, Gournas C (2008-10-01). "Structure-function relationships in the nucleobase-ascorbate transporter (NAT) family: lessons from model microbial genetic systems". Channels. 2 (5): 363–72. doi:10.4161/chan.2.5.6902. PMID 18981714.
  5. Gournas C, Papageorgiou I, Diallinas G (May 2008). "The nucleobase-ascorbate transporter (NAT) family: genomics, evolution, structure-function relationships and physiological role". Molecular BioSystems. 4 (5): 404–16. doi:10.1039/b719777b. PMID 18414738.
  6. Saier M Jr. "2.A.40 The Nucleobase/Ascorbate Transporter (NAT) or Nucleobase:Cation Symporter-2 (NCS2) Family". Transporter Classification Database. Saier Lab Bioinformatics Group / SDSC.
  7. Lu F, Li S, Jiang Y, Jiang J, Fan H, Lu G, Deng D, Dang S, Zhang X, Wang J, Yan N (Apr 2011). "Structure and mechanism of the uracil transporter UraA". Nature. 472 (7342): 243–6. Bibcode:2011Natur.472..243L. doi:10.1038/nature09885. PMID 21423164. S2CID 4421922.
  8. Christiansen LC, Schou S, Nygaard P, Saxild HH (Apr 1997). "Xanthine metabolism in Bacillus subtilis: characterization of the xpt-pbuX operon and evidence for purine- and nitrogen-controlled expression of genes involved in xanthine salvage and catabolism". Journal of Bacteriology. 179 (8): 2540–50. doi:10.1128/jb.179.8.2540-2550.1997. PMC 179002. PMID 9098051.
  9. Schultz AC, Nygaard P, Saxild HH (Jun 2001). "Functional analysis of 14 genes that constitute the purine catabolic pathway in Bacillus subtilis and evidence for a novel regulon controlled by the PucR transcription activator". Journal of Bacteriology. 183 (11): 3293–302. doi:10.1128/JB.183.11.3293-3302.2001. PMC 99626. PMID 11344136.
  10. Ghim SY, Neuhard J (Jun 1994). "The pyrimidine biosynthesis operon of the thermophile Bacillus caldolyticus includes genes for uracil phosphoribosyltransferase and uracil permease". Journal of Bacteriology. 176 (12): 3698–707. doi:10.1128/jb.176.12.3698-3707.1994. PMC 205559. PMID 8206848.
  11. Loh KD, Gyaneshwar P, Markenscoff Papadimitriou E, Fong R, Kim KS, Parales R, Zhou Z, Inwood W, Kustu S (Mar 2006). "A previously undescribed pathway for pyrimidine catabolism". Proceedings of the National Academy of Sciences of the United States of America. 103 (13): 5114–9. doi:10.1073/pnas.0600521103. PMC 1458803. PMID 16540542.
  12. Kim KS, Pelton JG, Inwood WB, Andersen U, Kustu S, Wemmer DE (Aug 2010). "The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems". Journal of Bacteriology. 192 (16): 4089–102. doi:10.1128/JB.00201-10. PMC 2916427. PMID 20400551.
This article incorporates text from the public domain Pfam and InterPro: IPR006043
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