PIRSF family classification system for protein functional and evolutionary analysis

Abstract

The PIRSF protein classification system (http://pir.georgetown.edu/pirsf/) reflects evolutionary relationships of full-length proteins and domains. The primary PIRSF classification unit is the homeomorphic family, whose members are both homologous (evolved from a common ancestor) and homeomorphic (sharing full-length sequence similarity and a common domain architecture). PIRSF families are curated systematically based on literature review and integrative sequence and functional analysis, including sequence and structure similarity, domain architecture, functional association, genome context, and phyletic pattern. The results of classification and expert annotation are summarized in PIRSF family reports with graphical viewers for taxonomic distribution, domain architecture, family hierarchy, and multiple alignment and phylogenetic tree. The PIRSF system provides a comprehensive resource for bioinformatics analysis and comparative studies of protein function and evolution. Domain or fold-based searches allow identification of evolutionarily related protein families sharing domains or structural folds. Functional convergence and functional divergence are revealed by the relationships between protein classification and curated family functions. The taxonomic distribution allows the identification of lineage-specific or broadly conserved protein families and can reveal horizontal gene transfer. Here we demonstrate, with illustrative examples, how to use the web-based PIRSF system as a tool for functional and evolutionary studies of protein families.

Keywords: Domain architecture; Functional convergence; Functional divergence; Genome context; Protein family classification; Taxonomic distribution.

Figure 1

PIRSF protein family classification and curation workflow

Figure 2

The PIRDAGbrowser view displaying PIRSF025009 family hierarchy with Yip1 and Yip4 subfamilies and protein membership.

Figure 3

(A) Selected PIRSF response regulator families with CheY-like phosphoacceptor domain (PF00072); (B) domain display of the selected PIRSF families

Figure 4

The PIR tree and alignment view of PIRSF000886 metallophosphoesterase-fold proteins, showing sequence variation of the Vps29 subfamily

Figure 5

Functional convergence of cobaltochelatases in evolutionary unrelated PIRSF families that do not share common domain architecture or SCOP fold. Note that the number of PIRSF entries retrieved in this or any other search may change due to the addition of new annotations.

Figure 6

(A) Chorismate mutase-related PIRSF families and (B) taxonomic distribution of family members