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GPCR NaVa数据库:人类G蛋白偶联受体中的天然变体

GPCR NaVa database: natural variants in human G protein-coupled receptors.

作者信息

Kazius Jeroen, Wurdinger Kerstin, van Iterson Maarten, Kok Joost, Bäck Thomas, Ijzerman Ad P

机构信息

Division of Medicinal Chemistry, Leiden-Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.

出版信息

Hum Mutat. 2008 Jan;29(1):39-44. doi: 10.1002/humu.20638.

Abstract

The superfamily of human G protein-coupled receptors (GPCRs) is large and regulates a plethora of important physiological processes by transducing extracellular signals over cell membranes. A diversity of natural variants occurs in these receptors, including rare mutations and common polymorphisms. These variants differ in their impact on DNA, ranging from single nucleotide polymorphisms (SNPs) to copy number variants, and in their impact on protein function. Natural variants furthermore vary in their effects on human phenotypes from neutral to disease-associated. As mutation data are highly dispersed over numerous sources, a single resource for variants would aid investigators of GPCRs. The GPCR NaVa database therefore integrates data on natural variants in human GPCRs from online databases, the scientific literature, and patents. Where available, variants contain information on their location in the DNA (and protein sequence), the involved nucleotides (and amino acids), the average frequency of each allele, reported disease associations, and references to public databases and the scientific literature. The GPCR NaVa database aims to facilitate studies into pharmacogenetics, genotype-phenotype, and structure-function relationships of GPCRs. The GPCR NaVa database is interlinked with the family-specific GPCRDB resource and is accessible as a stand-alone database through a user-friendly website at http://nava.liacs.nl (last accessed 28 August 2007).

摘要

人类G蛋白偶联受体(GPCR)超家族规模庞大,通过在细胞膜上转导细胞外信号来调节众多重要的生理过程。这些受体存在多种自然变体,包括罕见突变和常见多态性。这些变体在对DNA的影响方面存在差异,从单核苷酸多态性(SNP)到拷贝数变体,在对蛋白质功能的影响方面也有所不同。此外,自然变体对人类表型的影响从中性到与疾病相关各不相同。由于突变数据高度分散在众多来源中,一个集中的变体资源将有助于GPCR的研究人员。因此,GPCR NaVa数据库整合了来自在线数据库、科学文献和专利的人类GPCR自然变体数据。在可行的情况下,变体包含有关其在DNA(和蛋白质序列)中的位置、涉及的核苷酸(和氨基酸)、每个等位基因的平均频率、报道的疾病关联以及指向公共数据库和科学文献的参考文献等信息。GPCR NaVa数据库旨在促进对GPCR的药物遗传学、基因型 - 表型和结构 - 功能关系的研究。GPCR NaVa数据库与特定家族的GPCRDB资源相互链接,并可通过用户友好的网站http://nava.liacs.nl作为独立数据库访问(最后访问时间为2007年8月28日)。

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