Transporters catalyze entry and exit of molecules into and out of cells and organelles. They achieve cellular homeostasis, are responsible for multidrug resistance in pathogens and tumors, and when defective, cause dozens of important human genetic diseases. Our laboratory maintains, updates and improves the Transporter Classification Database, TCDB, which houses the Transporter Classification (TC) system, adopted officially by the International Union of Biochemistry and Molecular Biology (IUBMB). TCDB is the internationally acclaimed, carefully annotated, universal standard for classifying and providing information about transporters and transport-related proteins in all major domains of life. It presents sequence, biochemical, physiological, pathological, structural and evolutionary data about these proteins and the transport systems they comprise. It uses a successful system of classification based on transporter class, subclass, family, subfamily, and individual transporter. In this competitive renewal of GM0077402, we propose to broaden and deepen our efforts to expand, update, automate and interlink TCDB. We will generate new data concerning transport proteins, design new machine learning approaches for data, and introduce procedures for making functional predictions of uncharacterized transporters. This last effort will derive reliable new biological knowledge from a variety of sources, including phylogeny, motif, domain, operon and regulon analyses.
Our Specific Aims are as follows: 1. To develop software for automatic text mining and information extraction. 2. To conduct bioinformatic analyses and molecular biological experiments for TC knowledge expansion. 3. To interconnect TCDB bidirectionally with other relevant databases, thereby creating a "network" of knowledge from current "island" databases. 4. To use multiple approaches to derive reliable functional predictions as guides for future research. 5. To utilize a newly formed TCDB advisory board and establish a plan for modernization and sustainability. These goals are top priorities for rendering TCDB increasingly useful to the scientific community.

Public Health Relevance

TCDB is a database providing the worldwide scientific community with systematized information about proteins that catalyze transmembrane transport of salts, nutrients, toxins, drugs and macromolecules. It is the only IUBMB approved system for classifying transport proteins. Funding of this proposal will allow the maintenance and further development of TCDB, interlinking with related databases, expansion of machine learning approaches for information acquisition, and introduction of approaches for predicting the functions of uncharacterized proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM077402-07
Application #
8447507
Study Section
Biodata Management and Analysis Study Section (BDMA)
Program Officer
Brazhnik, Paul
Project Start
2006-04-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
7
Fiscal Year
2013
Total Cost
$290,465
Indirect Cost
$82,990
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Saier Jr, Milton H; Reddy, Vamsee S; Tsu, Brian V et al. (2016) The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res 44:D372-9
Vastermark, Ake; Driker, Adelle; Weng, Jingwei et al. (2016) The V-motifs facilitate the substrate capturing step of the PTS elevator mechanism. J Struct Biol 196:496-502
Reddy, Bhaskara L; Saier Jr, Milton H (2016) Properties and Phylogeny of 76 Families of Bacterial and Eukaryotic Organellar Outer Membrane Pore-Forming Proteins. PLoS One 11:e0152733
Kuppusamykrishnan, Harikrishnan; Chau, Larry M; Moreno-Hagelsieb, Gabriel et al. (2016) Analysis of 58 Families of Holins Using a Novel Program, PhyST. J Mol Microbiol Biotechnol 26:381-388
Zhang, Zhongge; Saier Jr, Milton H (2016) Transposon-mediated activation of the Escherichia coli glpFK operon is inhibited by specific DNA-binding proteins: Implications for stress-induced transposition events. Mutat Res 793-794:22-31
Zhu, Christopher; Nigam, Kabir B; Date, Rishabh C et al. (2015) Evolutionary Analysis and Classification of OATs, OCTs, OCTNs, and Other SLC22 Transporters: Structure-Function Implications and Analysis of Sequence Motifs. PLoS One 10:e0140569
Babbitt, Patricia C; Bagos, Pantelis G; Bairoch, Amos et al. (2015) Creating a specialist protein resource network: a meeting report for the protein bioinformatics and community resources retreat. Database (Oxford) 2015:bav063
Saier Jr, Milton H; Reddy, Bhaskara L (2015) Holins in bacteria, eukaryotes, and archaea: multifunctional xenologues with potential biotechnological and biomedical applications. J Bacteriol 197:7-17
Saier Jr, Milton H; Zhang, Zhongge (2015) Control of Transposon-Mediated Directed Mutation by the Escherichia coli Phosphoenolpyruvate:Sugar Phosphotransferase System. J Mol Microbiol Biotechnol 25:226-33
Chiang, Zachary; Vastermark, Ake; Punta, Marco et al. (2015) The complexity, challenges and benefits of comparing two transporter classification systems in TCDB and Pfam. Brief Bioinform 16:865-72

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