The peptidoglycan recognition proteins (PGRPs)

Peptidoglycan recognition proteins (PGRPs) are innate immunity molecules that contain a conserved peptidoglycan-binding type 2 amidase domain that is homologous to bacteriophage and bacterial type 2 amidases [1-6]. PGRPs are ubiquitous in most animals. Insects have multiple PGRP genes that are classified into short (S) and long (L) transcripts and are often alternatively spliced into up to 19 different proteins (Table 1) [1-5]. PGRPs have also been identified in mollusks, echinoderms, and vertebrates (Table 1), but plants and lower metazoa, including nematodes such as Caenorhabditis elegans, do not have PGRPs. PGRP genes usually form clusters that suggest their origin by gene duplication.Mammals have a family of four PGRPs, which were initially named PGRP-S, PGRP-L, and PGRP-Iα and PGRP-Iβ (for 'short', 'long', or 'intermediate' transcripts, respectively), by analogy to insect PGRPs [3]. Subsequently, the Human Genome Organization Gene Nomenclature Committee changed their symbols to PGLYRP-1, PGLYRP-2, PGLYRP-3, and PGLYRP-4, respectively. This terminology is also used for mouse PGRPs, and is beginning to be adopted for all vertebrate PGRPs. In this article, the abbreviation PGRP will be used for all invertebrate members and PGLYRP for all vertebrate members of the PGRP family.Phylogenetic analysis of insect PGRPs reveals an early separation of PGRPs into enzyme-active amidases and the remaining PGRPs, which activate signal transduction pathways and proteolytic cascades (Figure 1). PGRPs from other animals cannot easily be grouped with any individual insect PGRPs, so they are considered separately here. The non-insect PGRPs also evolved into two groups. The first group are all amidases, which in echinoderms, mollusks, fish, and amphibians are evolutionarily older and which more recently evolved into the mammalian amidases (PGLYRP-2; Figure 2). The second group are mammalian bactericidal proteins, which separated into two well defined branches: PGLYRP-1 (present in p