Biology:Nucleobase cation symporter-2
| Xanthine/uracil/vitamin C permease | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Xan_ur_permease | ||||||||
| Pfam | PF00860 | ||||||||
| Pfam clan | CL0062 | ||||||||
| InterPro | IPR006043 | ||||||||
| PROSITE | PDOC00860 | ||||||||
| TCDB | 2.A.40 | ||||||||
| OPM superfamily | 64 | ||||||||
| OPM protein | 3qe7 | ||||||||
| |||||||||
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]
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]
- Xanthine permeases, including PbuX (XanP) of Bacillus subtilis (TC# 2.A.40.3.1), involved in cellular xanthine transport.[8]
- Uric acid permeases, including PucJ of Bacillus subtilus (TC# 2.A.40.3.2), which promotes uptake of uric acid into the cell in limiting-nitrogen conditions.[9]
- Uracil permeases, including UraA of E. coli (TC# 2.A.40.1.1), which facilitates Uracil uptake.[7][10]
- Pyrimidine permeases, including RutG of E. coli (TC# 2.A.40.1.3) [11][12]
- Purine permeases, including YcpX of Clostridium perfringens (TC# 2.A.40.2.1)
References
- ↑ "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. Dec 2006. doi:10.1074/jbc.M605748200. PMID 17077086.
- ↑ 2.0 2.1 "The amino acid-polyamine-organocation superfamily". Journal of Molecular Microbiology and Biotechnology 22 (2): 105–13. 2012-01-01. doi:10.1159/000338542. PMID 22627175.
- ↑ "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. 2012-01-01. PMID 23097742.
- ↑ "Structure-function relationships in the nucleobase-ascorbate transporter (NAT) family: lessons from model microbial genetic systems". Channels 2 (5): 363–72. 2008-10-01. doi:10.4161/chan.2.5.6902. PMID 18981714.
- ↑ "The nucleobase-ascorbate transporter (NAT) family: genomics, evolution, structure-function relationships and physiological role". Molecular BioSystems 4 (5): 404–16. May 2008. doi:10.1039/b719777b. PMID 18414738.
- ↑ 6.0 6.1 6.2 Saier, MH Jr.. "2.A.40 The Nucleobase/Ascorbate Transporter (NAT) or Nucleobase:Cation Symporter-2 (NCS2) Family". Saier Lab Bioinformatics Group / SDSC. http://www.tcdb.org/search/result.php?tc=2.A.40.
- ↑ 7.0 7.1 "Structure and mechanism of the uracil transporter UraA". Nature 472 (7342): 243–6. Apr 2011. doi:10.1038/nature09885. PMID 21423164. Bibcode: 2011Natur.472..243L.
- ↑ "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. Apr 1997. doi:10.1128/jb.179.8.2540-2550.1997. PMID 9098051.
- ↑ "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. Jun 2001. doi:10.1128/JB.183.11.3293-3302.2001. PMID 11344136.
- ↑ "The pyrimidine biosynthesis operon of the thermophile Bacillus caldolyticus includes genes for uracil phosphoribosyltransferase and uracil permease". Journal of Bacteriology 176 (12): 3698–707. Jun 1994. doi:10.1128/jb.176.12.3698-3707.1994. PMID 8206848.
- ↑ "A previously undescribed pathway for pyrimidine catabolism". Proceedings of the National Academy of Sciences of the United States of America 103 (13): 5114–9. Mar 2006. doi:10.1073/pnas.0600521103. PMID 16540542.
- ↑ "The Rut pathway for pyrimidine degradation: novel chemistry and toxicity problems". Journal of Bacteriology 192 (16): 4089–102. Aug 2010. doi:10.1128/JB.00201-10. PMID 20400551.
 |  |
