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 evolutionar 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 systems and constituent proteins. In this competitive renewal of GM0077402, we propose to expand, update, automate and interlink TCDB. In particular, we will collaborate to integrate and unify the classification systems used by TCDB and Pfam with the formation of a TC ontological system. We will generate new data concerning transport proteins, and expand procedures for making functional predictions. 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 compare and evaluate methods of homology establishment, e.g., our and Pfam's statistical approaches, as well as introduce a system of protein repeat unit and domain identification. We will confirm and extend homology results based on structural superimpositions and profile: profile comparisons. We will develop and implement pipelines for the exchange of information between Pfam and TCDB and standardize both classification systems. 2. To incorporate our family descriptions into Wikipedia, to facilitate community annotation and interaction. Thus, we will add to Wikipedia, and integrate with Pfam to create a common platform for community annotation. 3. To create a substrate ontological framework for TCDB, using ChEBI and GO. 4. To use and automate multiple approaches, including phylogeny and synteny, to derive reliable functional predictions and provide guides for other researchers to do the same. 5. To utilize our TCDB advisory board for continued knowledgebase modernization and sustainability.

Public Health Relevance

TCDB is a database providing the worldwide scientific community with systematized information about proteins that catalyze transmembrane transport. It is the only IUBMB-approved system for classifying transport proteins. Funding of this proposal will allow the introduction of ontological systems, maintenance and further development of TCDB, integration with Pfam, incorporation of TC descriptions into Wikipedia and introduction of novel 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 #
5R01GM077402-11
Application #
9233150
Study Section
Special Emphasis Panel (ZRG1-BST-H (90)S)
Program Officer
Ravichandran, Veerasamy
Project Start
2006-04-01
Project End
2019-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
11
Fiscal Year
2017
Total Cost
$272,025
Indirect Cost
$96,525
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
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:
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
Saier Jr, Milton H; Kukita, Chika; Zhang, Zhongge (2017) Transposon-mediated directed mutation in bacteria and eukaryotes. Front Biosci (Landmark Ed) 22:1458-1468
Heidari Tajabadi, Fereshteh; Medrano-Soto, Arturo; Ahmadzadeh, Masoud et al. (2017) Comparative Analyses of Transport Proteins Encoded within the Genomes of Bdellovibrio bacteriovorus HD100 and Bdellovibrio exovorus JSS. J Mol Microbiol Biotechnol 27:332-349
Do, Jimmy; Zafar, Hassan; Saier Jr, Milton H (2017) Comparative genomics of transport proteins in probiotic and pathogenic Escherichia coli and Salmonella enterica strains. Microb Pathog 107:106-115
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

Showing the most recent 10 out of 92 publications