P2CS: a two-component system resource for prokaryotic signal transduction research

Abstract

Background: With the escalation of high throughput prokaryotic genome sequencing, there is an ever-increasing need for databases that characterise, catalogue and present data relating to particular gene sets and genomes/metagenomes. Two-component system (TCS) signal transduction pathways are the dominant mechanisms by which micro-organisms sense and respond to external as well as internal environmental changes. These systems respond to a wide range of stimuli by triggering diverse physiological adjustments, including alterations in gene expression, enzymatic reactions, or protein-protein interactions.

Description: We present P2CS (Prokaryotic 2-Component Systems), an integrated and comprehensive database of TCS signal transduction proteins, which contains a compilation of the TCS genes within 755 completely sequenced prokaryotic genomes and 39 metagenomes. P2CS provides detailed annotation of each TCS gene including family classification, sequence features, functional domains, as well as genomic context visualization. To bypass the generic problem of gene underestimation during genome annotation, we also constituted and searched an ORFeome, which improves the recovery of TCS proteins compared to searches on the equivalent proteomes.

Conclusion: P2CS has been developed for computational analysis of the modular TCSs of prokaryotic genomes and metagenomes. It provides a complete overview of information on TCSs, including predicted candidate proteins and probable proteins, which need further curation/validation. The database can be browsed and queried with a user-friendly web interface at http://www.p2cs.org/.

Figure 1

Schematic modular pipeline of P2CS. After data download of prokaryotic genomes and metagenomes, protein sequence files are constructed and searches for TCS domains performed. Finally each TCS protein is annotated and categorized into a TCS family.

Figure 2

Response regulators classification. Schematic representation of the conserved domain architectures of RRs.

Figure 3

Numbers and types of TCS proteins. Histidine kinases (A) and response regulators (B), in prokaryotic genomes and metagenomes.

Figure 4

Histidine kinases classification. Schematic representation of the conserved domain architectures of HKs.

Figure 5

P2CS analysis of the Magnetospirillum magneticum AMB-1 genome. Each class result provides a link to a detailed gene list. Clickable links are underlined.

Figure 6

Leptospira borgpetersenii serovar Hardjo-bovis JB197 genome. Genomic context for a chromosomal region (2133100 – 2139600). Genes are represented in the six reading frames with initial data from the NCBI database (green genes with domains in blue) and the result of the P2CS analysis process (genes in light red with domains in purple). Red vertical lines represent stop codons and green lines represent potential start codons.