| 2.A.40 The Nucleobase:Cation Symporter-2 (NCS2) Family
The NCS2 family consists of over fifty 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 a-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).
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| References: |
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Brynestad, S., L.A. Iwanejko, G.S. Stewart and P.E. Granum (1994). A complex array of Hpr consensus DNA recognition sequences proximal to the enterotoxin gene in Clostridium perfringens type A. Microbiol. 140: 97—104.
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Daruwala, R., J. Song, W.S. Koh, S.C. Rumsey, M. Levine (1999). Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. FEBS Lett. 460: 480-484.
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de Koning, H. and G. Diallinas (2000). Nucleobase transporters. Molec. Memb. Biol. 75:75-94.
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Diallinas, G., J. Valdez, V. Sophianopoulou, A. Rosa and C. Scazzocchio (1998). Chimeric purine transporters of Aspergillus nidulans define a domain critical for function and specificity conserved in bacterial, plant and metazoan homologues. EMBO J. 17: 3827-3837.
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Diallinas, G., L. Gorfinkiel, H.N. Arst, Jr., G. Cecchetto and C. Scazzocchio (1995). Genetic and molecular characterization of a gene encoding a wide specificity purine permease of Aspergillus nidulans reveals a novel family of transporters conserved in prokaryotes and eukaryotes. J. Biol. Chem. 270: 8610—8622.
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Ghim, S.Y. and J. Neuhard (1994). The pyrimidine biosynthesis operon of the thermophile Bacillus caldolyticus includes genes for uracil phosphoribosyltransferase and uracil permease. J. Bacteriol. 176: 3698—3707.
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Gorfinkiel, L., G. Diallinas and C. Scazzocchio (1993). Sequence and regulation of the uapA gene encoding a uric acid-xanthine permease in the fungus Aspergillus nidulans. J. Biol. Chem. 268: 23376—23381.
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Martinussen, J., J. Schallert, B. Andersen and K. Hammer (2001). The pyrimidine operon pyrRPB-carA from Lactococcus lactis. J. Bacteriol. 183: 2785-2794.
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Quinn, C.L., B.T. Stephenson and R.L. Switzer (1991). Functional organization and nucleotide sequence of the Bacillus subtilis pyrimidine biosynthetic operon. J. Biol. Chem. 266: 9113—9127.
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Saier, M.H., Jr., B.H. Eng, S. Fard, J. Garg, D.A. Haggerty, W.J. Hutchinson, D.L. Jack, E.C. Lai, H.J. Liu, D.P. Nusinew, A.M. Omar, S.S. Pao, I.T. Paulsen, J.A. Quan, M. Sliwinski, T.-T. Tseng, S. Wachi and G.B. Young (1999). Phylogenetic characterization of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422: 1-56.
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Schultz, A.C., P. Nygaard and H.H. Saxild (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. J. Bacteriol. 183: 3293-3302.
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Tsukaguchi, H., T. Tokui, B. Mackenzie, U.V. Berger, X.-Z. Chen, Y. Wang, R.F. Brubaker and M.A. Hediger (1999). A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature 399: 70-75.
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Turner, R.J., Y. Lu and R.L. Switzer (1994). Regulation of the Bacillus subtilis pyrimidine biosynthetic (pyr) gene cluster by an autogenous transcriptional attenuation mechanism. J. Bacteriol. 176: 3708—3722.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 2.A.40.1.1 | Uracil permease | Bacteria | UraA of E. coli |
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| 2.A.40.1.2 | High affinity uracil permease | Bacteria | PyrP of Lactococcus lactis (gbCAG89870) |
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| 2.A.40.2.1 | Purine permease | Bacteria | YcpX of Clostridium perfringens |
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| 2.A.40.3.1 | Xanthine permease | Bacteria | PbuX (XanP) of Bacillus subtilis |
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| 2.A.40.3.2 | Uric acid permease | Bacteria | PucJ of Bacillus subtilis |
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| 2.A.40.4.1 | High affinity uric acid-xanthine permease | Fungi | UapA of Emericella nidulans |
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| 2.A.40.5.1 | General purine permease | Fungi | UapC of Emericella nidulans |
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| 2.A.40.6.1 | L-ascorbate:Na+ symporter, SVCT1 | Animals | SVCT1 of Rattus norvegicus |
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