Dataset Information

Functional classification of proteins and protein variants.

ABSTRACT: To help characterize the diversity in biological function of proteins emerging from the analysis of whole genomes, we present an operational definition of biological function that provides an explicit link between the functional classification of proteins and the effects of genetic variation or mutation on protein function. Using phylogenetic information, we establish definite criteria for functional relatedness among proteins and a companion procedure for predicting deleterious alleles or mutations. Applied to the functional classification of sequences similar to 13 human tumor suppressor proteins, our methods predict there are functional properties unique to mammals for three of them, BRCA1, BRCA2, and WT1. We examine protein variants caused by nonsynonymous single-nucleotide polymorphisms in a set of clinically important genes and estimate the magnitude of a disproportionate propensity for disruption of function among the nonsynomous single-nucleotide polymorphisms that are maintained at low frequency in the human population.

SUBMITTER: Lau AY

PROVIDER: S-EPMC404087 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional classification of proteins and protein variants.

Lau Albert Y AY Chasman Daniel I DI

Proceedings of the National Academy of Sciences of the United States of America 20040415 17

To help characterize the diversity in biological function of proteins emerging from the analysis of whole genomes, we present an operational definition of biological function that provides an explicit link between the functional classification of proteins and the effects of genetic variation or mutation on protein function. Using phylogenetic information, we establish definite criteria for functional relatedness among proteins and a companion procedure for predicting deleterious alleles or mutat ...[more]

PMID: 15087495

Similar Datasets

Project description:Organellar gene expression (OGE) is crucial for plant development, photosynthesis, and respiration, but our understanding of the mechanisms that control it is still relatively poor. Thus, OGE requires various nucleus-encoded proteins that promote transcription, splicing, trimming, and editing of organellar RNAs, and regulate translation. In metazoans, proteins of the mitochondrial Transcription tERmination Factor (mTERF) family interact with the mitochondrial chromosome and regulate transcriptional initiation and termination. Sequencing of the Arabidopsis thaliana genome led to the identification of a diversified MTERF gene family but, in contrast to mammalian mTERFs, knowledge about the function of these proteins in photosynthetic organisms is scarce. In this hypothesis article, I show that tandem duplications and one block duplication contributed to the large number of MTERF genes in A. thaliana, and propose that the expansion of the family is related to the evolution of land plants. The MTERF genes-especially the duplicated genes-display a number of distinct mRNA accumulation patterns, suggesting functional diversification of mTERF proteins to increase adaptability to environmental changes. Indeed, hypothetical functions for the different mTERF proteins can be predicted using co-expression analysis and gene ontology (GO) annotations. On this basis, mTERF proteins can be sorted into five groups. Members of the "chloroplast" and "chloroplast-associated" clusters are principally involved in chloroplast gene expression, embryogenesis, and protein catabolism, while representatives of the "mitochondrial" cluster seem to participate in DNA and RNA metabolism in that organelle. Moreover, members of the "mitochondrion-associated" cluster and the "low expression" group may act in the nucleus and/or the cytosol. As proteins involved in OGE and presumably nuclear gene expression (NGE), mTERFs are ideal candidates for the coordination of the expression of organelle and nuclear genomes.

Dataset Information

Functional classification of proteins and protein variants.

Publications

Functional classification of proteins and protein variants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets