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, individual transport system and constituent proteins. It also includes a superfamily hyperlink. In this competitive renewal of GM0077402, we propose to continue to expand, update, and semi-automate TCDB.
Our specific aims are to (1) upgrade TCDB by characterizing and categorizing protein domains and their topologies, motifs, repeat units, functional interactions, alternative splicing and post-translational modifications, (2) expand TCDB by implementing novel pipelines for data entry that will increase the coverage of transport diversity in TCDB while describing more effectively the complexity of multicomponent transport systems, (3) enter into TCDB transporter modulators such as activators, inhibitors, drugs and xenobiotics as well as internal and external conditions that influence transporter activities, while generating an ontology to describe the effects of chemical modulators that will complement our substrate ontology, (4) incorporate into TCDB synthetic pores/channels (TC subclass 1.D), and carriers (TC subclass 2.B), (5) introduce into TCDB connections between transport and metabolism and (6) expand our plans for long-term TCDB sustainability.

Public Health Relevance

TCDB is the only IUBMB-approved database providing the worldwide scientific community with systematic information about proteins that catalyze transmembrane transport. Transport proteins play critical roles in health-related issues such as personalized medicine, cancer, drug development, bacterial pathogenesis and antimicrobial resistance. Funding of this proposal will allow us to provide research results, as well as high-quality data and software for the identification of transporter proteins useful to scientists whose investigations focus on health issues.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biodata Management and Analysis Study Section (BDMA)
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Ravichandran, Veerasamy
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University of California, San Diego
Schools of Arts and Sciences
La Jolla
United States
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Babu, Mohan; Bundalovic-Torma, Cedoljub; Calmettes, Charles et al. (2018) Global landscape of cell envelope protein complexes in Escherichia coli. Nat Biotechnol 36:103-112
Rodionova, Irina A; Goodacre, Norman; Babu, Mohan et al. (2018) The Nitrogen Regulatory PII Protein (GlnB) and N-Acetylglucosamine 6-Phosphate Epimerase (NanE) Allosterically Activate Glucosamine 6-Phosphate Deaminase (NagB) in Escherichia coli. J Bacteriol 200:
Humayun, M Zafri; Zhang, Zhongge; Butcher, Anna M et al. (2017) Hopping into a hot seat: Role of DNA structural features on IS5-mediated gene activation and inactivation under stress. PLoS One 12:e0180156
Saier Jr, Milton H; Trevors, J T (2017) Science, Innovation and the Future of Humanity. J Mol Microbiol Biotechnol 27:128-132
Rodionova, Irina A; Zhang, Zhongge; Mehla, Jitender et al. (2017) The phosphocarrier protein HPr of the bacterial phosphotransferase system globally regulates energy metabolism by directly interacting with multiple enzymes in Escherichia coli. J Biol Chem 292:14250-14257
Chou, Amy; Lee, Andre; Hendargo, Kevin J et al. (2017) Characterization of the Tetraspan Junctional Complex (4JC) superfamily. Biochim Biophys Acta Biomembr 1859:402-414
Vastermark, Ake; Driker, Adelle; Weng, Jingwei et al. (2017) Difference distance map data of alternative crystal forms of UlaA. Data Brief 10:198-201
Moreno-Hagelsieb, Gabriel; Vitug, Bennett; Medrano-Soto, Arturo et al. (2017) The Membrane Attack Complex/Perforin Superfamily. J Mol Microbiol Biotechnol 27:252-267
Lee, Justin; Ghosh, Shounak; Saier Jr, Milton H (2017) Comparative genomic analyses of transport proteins encoded within the red algae Chondrus crispus, Galdieria sulphuraria, and Cyanidioschyzon merolae11. J Phycol 53:503-521
Zhang, Zhongge; Kukita, Chika; Humayun, M Zafri et al. (2017) Environment-directed activation of the Escherichia coliflhDC operon by transposons. Microbiology 163:554-569

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