The Transporter Classification Database (TCDB)

描述(申请人提供)：转运蛋白催化分子进出细胞和细胞器。它们实现细胞内稳态，导致病原体和肿瘤产生多药耐药，当缺陷时，会导致数十种重要的人类遗传病。我们的实验室维护、更新和改进运输者分类数据库TcDB，其中包含国际生物化学和分子生物学联合会(IUBMB)正式采用的运输者分类(TC)系统。TcdB是国际上公认的、经过仔细注释的通用标准，用于分类和提供有关所有主要生命领域的转运蛋白和与转运蛋白相关的信息。它提供了关于这些蛋白质及其组成的运输系统的序列、生化、生理、病理、结构和进化数据。它使用了一种成功的基于转运蛋白类别、亚类、家族、亚家族、个体运输系统和组成蛋白的分类系统。在GM0077402的这次竞争性更新中，我们建议对Tcdb进行扩展、更新、自动化和互连。特别是，我们将合作整合和统一Tcdb和Pfam使用的分类系统，形成TC本体系统。我们将生成有关运输蛋白的新数据，并扩展进行功能预测的程序。这最后的努力将从各种来源获得可靠的新生物学知识，包括系统发育、基序、结构域、操纵子和调节子分析。我们的具体目标如下：1.比较和评价同源性建立的方法，如OUR和Pfam的统计方法，以及引入蛋白质重复单位和结构域识别系统。我们将基于结构叠加和Profile：Profile比较来确认和扩展同源结果。我们将开发和实施Pfam和Tcdb之间的信息交换管道，并对这两个分类系统进行标准化。2.将我们的家庭描述纳入维基百科，以方便社区注释和互动。因此，我们将添加到维基百科，并与Pfam整合，创建一个公共的社区注释平台。3.使用Chebi和Go为Tcdb创建一个底层本体框架。4.使用多种方法并使之自动化，包括系统发育和共时，以得出可靠的功能预测，并为其他研究人员提供同样的指导。5.利用我们的Tcdb顾问委员会继续实现知识库的现代化和可持续性。

DESCRIPTION (provided by applicant): 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.