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6  structures 1112  species 0  interactions 3961  sequences 40  architectures

Family: Transp_cyt_pur (PF02133)

Summary: Permease for cytosine/purines, uracil, thiamine, allantoin

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This is the Wikipedia entry entitled "Nucleobase cation symporter-1 ". More...

Nucleobase cation symporter-1 Edit Wikipedia article

Permease for cytosine/purines, uracil, thiamine, allantoin
Symbol Transp_cyt_pur
Pfam PF02133
InterPro IPR001248
TCDB 2.A.39
OPM superfamily 67
OPM protein 2x79
CDD cd10323

The Nucleobase:Cation Symporter-1 (NCS1) Family (TC# 2.A.39) consists of over 1000 currently sequenced proteins derived from Gram-negative and Gram-positive bacteria, archaea, fungi and plants. These proteins function as transporters for nucleobases including purines and pyrimidines. Members of this family possess twelve transmembrane α-helical spanners (TMSs). At least some of them have been shown to function in uptake by substrate:H+ symport mechanism.


The bacterial and yeast proteins are widely divergent and do not cluster closely on the NCS1 family phylogenetic tree. B. subtilis possesses two paralogues of the NCS1 family, and S. cerevisiae has several. Two of the yeast proteins (Dal4 (TC# 2.A.39.3.1) and Fur4 (TC# 2.A.39.3.2)) cluster tightly together. Three other S. cerevisiae proteins, one of which is the thiamin permease, Thi10 (TC# 2.A.39.4.1), and another of which is the nicotinamide riboside transporter, Nrt1 (TC# 2.A.39.4.2),[1] also cluster tightly together. The latter three proteins are likely to be closely related thiamin permease isoforms. The yeast cytosine-purine and vitamin B6 transporters cluster loosely together (24% identity; e-50).[2] The bacterial proteins are derived from several Gram-negative and Gram-positive species. These proteins exhibit limited sequence similarity with the xanthine permease, PbuX (TC# 2.A.39.4.1), of Bacillus subtilis which is a member of the NCS2 family.[3]

Structure and Function

Proteins of the NCS1 family are 419-635 amino acyl residues long and possess twelve putative transmembrane α-helical spanners (TMSs). At least some of them have been shown to function in uptake by substrate:H+ symport. In these respects, and with respect to substrate specificity, these proteins resemble the symporters of the NCS2 family, providing further evidence that the two families represent distant constituents of a single superfamily, the APC Superfamily. The two families probably arose by an early gene duplication event that occurred long before divergence of the three major kingdoms of life. It is possible that they are distant constituents of the MFS (2.A.1).[3]

The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Weyand et al. (2008) reported the 2.85-angstrom resolution structure of the NCS1 benzyl-hydantoin transporter, Mhp1 (TC# 2.A.39.3.6), from Microbacterium liquefaciens.[4] This structure (and related structures) are available through RCSB (PDB: 2JLN​, 2X79​, 4D1A​, 4D1B​, 4D1C​, 4D1D​). Mhp1 contains 12 transmembrane helices, 10 of which are arranged in two inverted repeats of five helices. The structures of the outward-facing open and substrate-bound occluded conformations were solved, showing how the outward-facing cavity closes upon binding of substrate.[5] Comparisons with the leucine transporter LeuT(Aa) and the galactose transporter vSGLT reveal that the outward- and inward-facing cavities are symmetrically arranged on opposite sides of the membrane. The reciprocal opening and closing of these cavities is synchronized by the inverted repeat helices 3 and 8, providing the structural basis of the alternating access model for membrane transport.[4]


NCS1 proteins are H+/Na+ symporters specific for the uptake of purines, pyrimidines and related metabolites. Krypotou et al. 2015 studied the origin, diversification and substrate specificities of fungal NCS1 transporters, suggesting that the two fungal NCS1 subfamilies, Fur and Fcy, and plant homologues, originated through independent horizontal transfers from prokaryotes.[6] Expansion by gene duplication led to functional diversification of fungal NCS1 porters. They characterized all Fur proteins in Aspergillus nidulans. Homology modelling, substrate docking, molecular dynamics and systematic mutational analysis in three Fur transporters with distinct specificities identified residues critical for function and specificity, located within a major substrate binding site, in transmembrane segments TMS1, TMS3, TMS6 and TMS8. They predicted and confirmed that residues determining substrate specificity are located not only in the major substrate binding site, but also in a putative outward-facing selectivity gate. Their evolutionary and structure-function analyses led to the concept that selective channel-like gates may contribute to substrate specificity.[6]

Transport Reaction

The generalized transport reaction catalyzed by NCS1 family permeases is:[3]

Nucleobase or Vitamin (out) + H+ (out) → Nucleobase or Vitamin (in) + H+ (in)

See also


  1. ^ Belenky, Peter A.; Moga, Tiberiu G.; Brenner, Charles (2008-03-28). "Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1". The Journal of Biological Chemistry. 283 (13): 8075–8079. doi:10.1074/jbc.C800021200. ISSN 0021-9258. PMID 18258590. 
  2. ^ Stolz, Jürgen; Vielreicher, Martin (2003-05-23). "Tpn1p, the plasma membrane vitamin B6 transporter of Saccharomyces cerevisiae". The Journal of Biological Chemistry. 278 (21): 18990–18996. doi:10.1074/jbc.M300949200. ISSN 0021-9258. PMID 12649274. 
  3. ^ a b c Saier, MH Jr. "2.A.39 The Nucleobase:Cation Symporter-1 (NCS1) Family". Transporter Classification Database. Saier Lab Bioinformatics Group / SDSC. 
  4. ^ a b Weyand, Simone; Shimamura, Tatsuro; Yajima, Shunsuke; Suzuki, Shun'ichi; Mirza, Osman; Krusong, Kuakarun; Carpenter, Elisabeth P.; Rutherford, Nicholas G.; Hadden, Jonathan M. (2008-10-31). "Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter". Science (New York, N.Y.). 322 (5902): 709–713. doi:10.1126/science.1164440. ISSN 1095-9203. PMC 2885439free to read. PMID 18927357. 
  5. ^ Kazmier, Kelli; Sharma, Shruti; Islam, Shahidul M.; Roux, Benoît; Mchaourab, Hassane S. (2014-10-14). "Conformational cycle and ion-coupling mechanism of the Na+/hydantoin transporter Mhp1". Proceedings of the National Academy of Sciences of the United States of America. 111 (41): 14752–14757. doi:10.1073/pnas.1410431111. ISSN 1091-6490. PMC 4205665free to read. PMID 25267652. 
  6. ^ a b Krypotou, Emilia; Evangelidis, Thomas; Bobonis, Jacob; Pittis, Alexandros A.; Gabaldón, Toni; Scazzocchio, Claudio; Mikros, Emmanuel; Diallinas, George (2015-06-01). "Origin, diversification and substrate specificity in the family of NCS1/FUR transporters". Molecular Microbiology. 96 (5): 927–950. doi:10.1111/mmi.12982. ISSN 1365-2958. PMID 25712422. 

This article incorporates text from the public domain Pfam and InterPro IPR001248

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Permease for cytosine/purines, uracil, thiamine, allantoin Provide feedback

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Literature references

  1. Vickers MF, Yao SY, Baldwin SA, Young JD, Cass CE;, J Biol Chem. 2000;275:25931-25938.: Nucleoside transporter proteins of Saccharomyces cerevisiae. Demonstration of a transporter (FUI1) with high uridine selectivity in plasma membranes and a transporter (FUN26) with broad nucleoside selectivity in intracellular membranes. PUBMED:10827169 EPMC:10827169

  2. Danielsen S, Kilstrup M, Barilla K, Jochimsen B, Neuhard J;, Mol Microbiol. 1992;6:1335-1344.: Characterization of the Escherichia coli codBA operon encoding cytosine permease and cytosine deaminase. PUBMED:1640834 EPMC:1640834

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001248

This entry represents the purine-cytosine permease family, whose members include allantoin permease Dal4 [PUBMED:1293888], nicotinamide riboside transporter 1 (Nrt1) [PUBMED:18258590], purine-cytosine permease Fcy2/21/22 [PUBMED:9092500], thiamine transporter Thi7/Thi72 [PUBMED:9358046], uracil permease Fur4 [PUBMED:9829833], uridine permease Fui1 [PUBMED:16854981] and vitamin B6 transporter Tpn1 [PUBMED:12649274] from budding yeasts. This entry also includes cytosine permeases codB from E. coli [PUBMED:1640834] and purine-uracil permease AtNCS1 from Arabidopsis [PUBMED:24621654].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan APC (CL0062), which has the following description:

This large superfamily contains a variety of transporters including amino acid permeases that according to TCDB belong to the APC (Amino acid-Polyamine-organoCation) superfamily.

The clan contains the following 20 members:

AA_permease AA_permease_2 AA_permease_C Aa_trans BCCT BenE Branch_AA_trans CstA HCO3_cotransp K_trans MFS_MOT1 Na_Ala_symp Nramp SNF Spore_permease SSF Sulfate_transp Transp_cyt_pur Trp_Tyr_perm Xan_ur_permease


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Seed source: IPR001248
Previous IDs: none
Type: Family
Author: Mian N, Bateman A
Number in seed: 14
Number in full: 3961
Average length of the domain: 403.30 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 81.86 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.7 23.6
Noise cut-off 23.4 23.4
Model length: 440
Family (HMM) version: 13
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Archea Archea Eukaryota Eukaryota
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Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Transp_cyt_pur domain has been found. There are 6 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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