Science China Life Sciences

, Volume 54, Issue 1, pp 60–64 | Cite as

TSdb: A database of transporter substrates linking metabolic pathways and transporter systems on a genome scale via their shared substrates

Open Access
Special Topic Research Papers

Abstract

TSdb (http://tsdb.cbi.pku.edu.cn) is the first manually curated central repository that stores formatted information on the substrates of transporters. In total, 37608 transporters with 15075 substrates from 884 organisms were curated from UniProt functional annotation. A unique feature of TSdb is that all the substrates are mapped to identifiers from the KEGG Ligand compound database. Thus, TSdb links current metabolic pathway schema with compound transporter systems via the shared compounds in the pathways. Furthermore, all the transporter substrates in TSdb are classified according to their biochemical properties, biological roles and subcellular localizations. In addition to the functional annotation of transporters, extensive compound annotation that includes inhibitor information from the KEGG Ligand and BRENDA databases has been integrated, making TSdb a useful source for the discovery of potential inhibitory mechanisms linking transporter substrates and metabolic enzymes. User-friendly web interfaces are designed for easy access, query and download of the data. Text and BLAST searches against all transporters in the database are provided. We will regularly update the substrate data with evidence from new publications.

Keywords

transporter substrate biological database compound classification compound metabolic network 

References

  1. 1.
    Nelson D L, Cox M M. Lehninger’s principles of biochemistry. 3rd ed. New York: Worth Publishers, 2000Google Scholar
  2. 2.
    Ren Q H, Chen K X, Paulsen I T. TransportDB: a comprehensive database resource for cytoplasmic membrane transport systems and outer membrane channels. Nucleic Acids Res, 2007, 35: D274–D279, 1:CAS:528:DC%2BD2sXivFKhtQ%3D%3D, 10.1093/nar/gkl925, 17135193PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Amann T, Hellerbrand C. GLUT1 as a therapeutic target in hepatocellular carcinoma. Expert Opin Ther Targets, 2009, 13: 1411–1427, 1:CAS:528:DC%2BD1MXhsVCku7%2FK, 10.1517/14728220903307509, 19874261PubMedCrossRefGoogle Scholar
  4. 4.
    Dettmer K, Aronov P A, Hammock B D. Mass spectrometry-based metabolomics. Mass Spectrom Rev, 2007, 26: 51–78, 1:CAS:528:DC%2BD2sXht1anur8%3D, 10.1002/mas.20108, 16921475PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Delgado-Lista J, Perez-Martinez P, Perez-Jimenez F, et al. ABCA1 gene variants regulate postprandial lipid metabolism in healthy men. Arterioscler Thromb Vasc Biol, 2010, 30: 1051–1057, 1:CAS:528:DC%2BC3cXkslKqs7k%3D, 10.1161/ATVBAHA.109.202580, 20185793PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Kim I W, Booth-Genthe C, Ambudkar S V. Relationship between drugs and functional activity of various mammalian P-glycoproteins (ABCB1). Mini Rev Med Chem, 2008, 8: 193–200, 1:CAS:528:DC%2BD1cXivFalsro%3D, 10.2174/138955708783744100, 18336339PubMedCrossRefGoogle Scholar
  7. 7.
    Gradhand U, Kim R B. Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2). Drug Metab Rev, 2008, 40: 317–354, 1:CAS:528:DC%2BD1cXnsVyqsL0%3D, 10.1080/03602530801952617, 18464048PubMedCrossRefGoogle Scholar
  8. 8.
    Solinas M, Yasar S, Goldberg S R. Endocannabinoid system involvement in brain reward processes related to drug abuse. Pharmacol Res, 2007, 56: 393–405, 1:CAS:528:DC%2BD2sXht1KgsbzO, 10.1016/j.phrs.2007.09.005, 17936009PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Higgins C F. Multiple molecular mechanisms for multidrug resistance transporters. Nature, 2007, 446: 749–757, 1:CAS:528:DC%2BD2sXktVeqsbk%3D, 10.1038/nature05630, 17429392PubMedCrossRefGoogle Scholar
  10. 10.
    Fichant G, Basse M J, Quentin Y. ABCdb: an online resource for ABC transporter repertories from sequenced archaeal and bacterial genomes. FEMS Microbiol Lett, 2006, 256: 333–339, 1:CAS:528:DC%2BD28Xjs1yksro%3D, 10.1111/j.1574-6968.2006.00139.x, 16499625PubMedCrossRefGoogle Scholar
  11. 11.
    Ren Q, Kang K H, Paulsen I T. TransportDB: a relational database of cellular membrane transport systems. Nucleic Acids Res, 2004, 32: D284–D288, 1:CAS:528:DC%2BD3sXhtVSrur7J, 10.1093/nar/gkh016, 14681414PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Saier M H, Tran C V Jr., Barabote R D. TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Res, 2006, 34: D181–D186, 1:CAS:528:DC%2BD28XisFOitw%3D%3D, 10.1093/nar/gkj001, 16381841PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Yan Q, Sadee W. Human membrane transporter database: a web-accessible relational database for drug transport studies and pharmacogenomics. AAPS PharmSci, 2000, 2: E20, 1:STN:280:DC%2BD3MjgtVOjtg%3D%3D, 10.1208/ps020320, 11741236PubMedCrossRefGoogle Scholar
  14. 14.
    UniProt Consortium. The Universal Protein Resource (UniProt) in 2010. Nucleic Acids Res, 2010, 38: D142–D148, 10.1093/nar/gkp846CrossRefGoogle Scholar
  15. 15.
    Jain E, Bairoch A, Duvaud S, et al. Infrastructure for the life sciences: design and implementation of the UniProt website. BMC Bioinformatics, 2009, 10: 136, 10.1186/1471-2105-10-136, 19426475PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Bairoch A, Apweiler R, Wu C H, et al. The Universal Protein Resource (UniProt). Nucleic Acids Res, 2005, 33: D154–D159, 1:CAS:528:DC%2BD2MXisVCktg%3D%3D, 10.1093/nar/gki070, 15608167PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Hermjakob H, Fleischmann W, Apweiler R. Swissknife—’lazy parsing’ of SWISS-PROT entries. Bioinformatics, 1999, 15: 771–772, 1:CAS:528:DyaK1MXnt1CksL4%3D, 10.1093/bioinformatics/15.9.771, 10498781PubMedCrossRefGoogle Scholar
  18. 18.
    Kanehisa M, Araki M, Goto S, et al. KEGG for linking genomes to life and the environment. Nucleic Acids Res, 2008, 36: D480–D484, 1:CAS:528:DC%2BD1cXhtVSku7k%3D, 10.1093/nar/gkm882, 18077471PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res, 2000, 28: 27–30, 1:CAS:528:DC%2BD3cXhvVGqu74%3D, 10.1093/nar/28.1.27, 10592173PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Lu Z, Cohen K B, Hunter L. GeneRIF quality assurance as summary revision. Pac Symp Biocomput, 2007, 269-280Google Scholar
  21. 21.
    Kanehisa M, Goto S, Hattori M, et al. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res, 2006, 34: D354–D357, 1:CAS:528:DC%2BD28XisFyitw%3D%3D, 10.1093/nar/gkj102, 16381885PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Chang A, Scheer M, Grote A, et al. BRENDA, AMENDA and FRENDA the enzyme information system: new content and tools in 2009. Nucleic Acids Res, 2009, 37: D588–D592, 1:CAS:528:DC%2BD1cXhsFejtb%2FP, 10.1093/nar/gkn820, 18984617PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Prasad T S K, Goel R, Kandasamy K, et al. Human Protein Reference Database—2009 update. Nucleic Acids Res, 2009, 37: D767–772, 1:CAS:528:DC%2BD1cXhsFejtLvL, 10.1093/nar/gkn892CrossRefGoogle Scholar
  24. 24.
    Breitkreutz B J, Stark C, Reguly T, et al. The BioGRID Interaction Database: 2008 update. Nucleic Acids Res, 2008, 36: D637–D640, 1:CAS:528:DC%2BD1cXhtVSrsLk%3D, 10.1093/nar/gkm1001, 18000002PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Willis R C, Hogue C W. Searching, viewing, and visualizing data in the Biomolecular Interaction Network Database (BIND). Curr Protoc Bioinformatics online publication 1 January 2006; doi: 10.1002/0471250953.bi0809s12Google Scholar
  26. 26.
    Gutteridge A, Kanehisa M, Goto S. Regulation of metabolic networks by small molecule metabolites. BMC Bioinformatics, 2007, 8: 88, 10.1186/1471-2105-8-88, 17352833PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© The Author(s) 2011

This article is published under license to BioMed Central Ltd. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  1. 1.Center for Bioinformatics, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life SciencesPeking UniversityBeijingChina
  2. 2.Key Laboratory of Evolutionary Systematics of Vertebrates, Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijingChina
  3. 3.School of Computer Science & TechnologyBeijing Institute of TechnologyBeijingChina

Personalised recommendations