Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
6  structures 3391  species 0  interactions 12396  sequences 92  architectures

Family: Transp_cyt_pur (PF02133)

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

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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
OPM superfamily64
OPM protein2x79

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 PA, Moga TG, Brenner C (March 2008). "Saccharomyces cerevisiae YOR071C encodes the high affinity nicotinamide riboside transporter Nrt1". The Journal of Biological Chemistry. 283 (13): 8075–9. doi:10.1074/jbc.C800021200. PMID 18258590.
  2. ^ Stolz J, Vielreicher M (May 2003). "Tpn1p, the plasma membrane vitamin B6 transporter of Saccharomyces cerevisiae". The Journal of Biological Chemistry. 278 (21): 18990–6. doi:10.1074/jbc.M300949200. 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 S, Shimamura T, Yajima S, Suzuki S, Mirza O, Krusong K, Carpenter EP, Rutherford NG, Hadden JM, O'Reilly J, Ma P, Saidijam M, Patching SG, Hope RJ, Norbertczak HT, Roach PC, Iwata S, Henderson PJ, Cameron AD (October 2008). "Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter". Science. 322 (5902): 709–13. doi:10.1126/science.1164440. PMC 2885439. PMID 18927357.
  5. ^ Kazmier K, Sharma S, Islam SM, Roux B, Mchaourab HS (October 2014). "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): 14752–7. doi:10.1073/pnas.1410431111. PMC 4205665. PMID 25267652.
  6. ^ a b Krypotou E, Evangelidis T, Bobonis J, Pittis AA, Gabaldón T, Scazzocchio C, Mikros E, Diallinas G (June 2015). "Origin, diversification and substrate specificity in the family of NCS1/FUR transporters". Molecular Microbiology. 96 (5): 927–50. doi:10.1111/mmi.12982. PMID 25712422.
This article incorporates text from the public domain Pfam and InterPro: IPR001248

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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

No Pfam abstract.

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

Internal database links

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

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


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: IPR001248
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Mian N , Bateman A
Number in seed: 14
Number in full: 12396
Average length of the domain: 405.40 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 82.65 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.5 23.5
Noise cut-off 23.4 23.4
Model length: 440
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


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 sequence.

Loading structure mapping...