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Transient receptor potential (TRP) channels are a family of Ca²⁺-permeable cation channels. In response to a wide range of cellular stimuli, they produce electrochemical signals via membrane potential or intracellular [Ca²⁺]. Aberrant activity of TRP channels has been implicated in its possible role in a variety of human diseases, such as neurological disorders, cardiovascular disease, and cancer [1]. Therefore, TRP channels are regarded as attractive targets for therapeutic intervention.

TRP channels consist of 28 isotypes in mammals. Based on structural and functional similarity, they are divided into 6 subfamilies [2].

• TRPC (canonical): TRPC1-7 (TRPC2 is a pseudogene in human)
• TRPV (vanilloid): TRPV1-6
• TRPM (melastatin): TRPM1-8
• TRPML (mucolipin): TRPML1-3
• TRPP (polycystin): TRPP1-3
• TRPA (ankryin): TRPA1

Accumulating evidence indicates that TRP channels form signalosomes by interacting with many cellular proteins [3]. Because protein-protein interactions (PPIs) are crucial for determining the outcome of most pathophysiological processes [4], the investigation of PPIs of TRP channels will facilitate the understanding of TRP channel biology. In addition, a molecular landscape for TRP channel PPIs can provide insight into the molecular mechanisms by which TRP channels are associated with a diversity of diseases.

To stimulate future researches among scientists who are interested in TRP channel biology, we have developed the TRIP (TRansient receptor potential channel-Interacting Protein) Database, a manually curated database that aims to provide comprehensive information on PPIs of mammalian TRP channels. The current version of the TRIP Database documents 545 PPI pairs among 28 TRP channels and 331 cellular proteins by curating 336 peer-reviewed publications. The TRIP Database provides a detailed summary of PPI data, which fits into 4 categories: screening, validation, characterization, and functional consequence. Users can find in-depth information specified in the literature on relevant analytical methods, gene constructs, and cell/tissue types. The TRIP Database has a user-friendly interface with several helpful features, including a search engine, an interaction map, and a function for cross-referencing useful external databases. Our TRIP Database will provide a valuable tool to assist in understanding the molecular regulatory network of TRP channels.

References

1. Nilius B, Owsianik G, Voets T, Peters JA, Transient receptor potential cation channels in disease. Physiol. Rev. (2007) 87, 165-217
2. Clapham DE, SnapShot: Mammalian TRP Channels. Cell. (2007) 129, 220
3. Kiselyov K, Shin DM, Kim JY, Yuan JP, Muallem S, TRPC channels: interacting proteins. Handb. Exp. Pharmacol. (2007) 179, 559-574
4. Ruffner H, Bauer A, Bouwmeester T, Human protein-protein interaction networks and the value for drug discovery. Drug Discov. Today. (2007) 12, 709-716

Publications

1. Young-Cheul Shin, Soo-Yong Shin, Insuk So, Dongseop Kwon, and Ju-Hong Jeon, TRIP Database: a manually curated database of protein-protein interactions for mammalian TRP channels, Nucleic Acids Research, 2011, Vol. 39 (suppl 1), Database issue D356-D361 (PMID: 20851834)

Useful Links

1. Transporter Classification Database (http://www.tcdb.org)
2. Human Membrane Transporter Database (http://lab.digibench.net/transporter)
3. IUBMB Membrane Transport Protein Nomenclature (http://www.chem.qmul.ac.uk/iubmb/mtp)
4. TransportDB (http://www.membranetransport.org)
5. ΔG prediction of transmembrane helix insertion (http://dgpred.cbr.su.se)
6. Transmembrane helix prediction (http://www.csbio.sjtu.edu.cn/bioinf/MemBrain)
7. Prediction of membrane protein topology and signal peptides (http://octopus.cbr.su.se)
8. Domains and Motifs in Transmembrane Proteins (http://topdom.enzim.hu/?m=search&by=seq)
9. Classification and Secondary Structure Prediction of Membrane Proteins (http://bp.nuap.nagoya-u.ac.jp/sosui)
10. Wikipedia: Transient receptor potential channel-interacting protein database