BMC Genomics 2008, 9:308 http://www.biomedcentral.com/1471-2164/9/308 and Mel18 and Drosophila Psc and Suppressor 2 of zeste (Su(z)2), and the Ring subfamily that includes vertebrate Ring1A, Ring1B and Drosophila dRing. In order to iden- tify potential orthologous relationships between these plant and animal homologous genes we conducted a phy- logenetic analysis of this family. Due to the low degree of sequence conservation in the C-terminal domain RAWUL (see Figure 1), we add the N-terminal Ring domain, which is highly conserved between plants and animals (Figure 4), to the phylogenetic analysis of the PRC1 Ring family. The high confidence bootstrap value (997/1000) at the connecting node (Figure 3) indicates that both sub- families (Bmi1/Mel18 and Ring1A/1B) are clearly present in plants (Figure 3). For instance, Arabidopsis Q0WX00 and estQ9FKW0 proteins are part of the Ring1A/1B sub- family, while Q94AY3 and Q9LS86 proteins are the orthologs of the Bmi1/Mel18 subfamily. The identifica- tion of orthologous relationships between the two groups including both plant and animal proteins suggests an early gene duplication event, giving rise to Bmi1/Mel18 and Ring1A/1B subfamilies prior to the plant-animal divergence. The plant and animal proteins therefore could share a common biochemical function. Similarly, lower metazoans, such as nematodes, are also thought to lack PRC1 homologs. In C. elegans, PcG-medi- ated gene repression has been proposed to require a PRC2-like complex [77] and two novel proteins, Suppres- sor of Pal-1 (SOP-2) and Sop-2-related protein 1 (SOR-1) [27,28]. Despite the lack of obvious sequence similarity, several conserved properties between PRC1 and the puta- tive SOP-2/SOR-1 complex suggested a conservation of the mechanism [27,28]. However, these proteins are not found in other organisms, including its closest related C. briggsae [28], weakening the case for an alternative PRC1- like complex. In addition, ubiquitinated H2A has been detected by western blot analysis in C. elegans [31], indi- cating that some proteins may be involved in H2A ubiq- uitination. Interestingly, we found one PRC1 Ring finger homolog in C. elegans and in C. briggsae (Figure 1 and 3). The function of this PRC1 Ring finger homolog is so far unknown. However, the conservation of the protein archi- tecture, an N-terminal Ring finger and a C-terminal RAWUL domain, suggest that the function of this protein could be related to histone ubiquitination. Conclusion We detected statistically significant sequence similarity between the ubiquitin superfamily and the conserved C- terminal regions of PRC1 Ring and WDR48-p80 families, defining a new Ubq-like domain, the RAWUL domain. The identification of an Ubq-like domain in the PRC1 Ring family offers new experimental approaches aimed at elucidating their roles in important cellular processes, such us, stem cell self-renewal and cancer. In addition, characterizing the RAWUL domain allowed us to identify putative PRC1 Ring finger proteins that were thought to be missing in the plants and worms. The possibility that a PRC1-like complex is also involved in PcG-mediated gene silencing mechanism in these organisms is intriguing and opens new avenues in PcG investigation. Methods Sequence analysis We first performed BLAST sequence similarity searches [41] against different protein sequence databases: UniProt [42], NBCI [43], ENSEMBL [44] and JGI [45]. For the sequence analysis we related distant protein families via profile searches using global hidden Markov models: HMMer [48] over the UniRef non redundant sequence database [47] and HHpred over pdb70 profile database [49]. The alignments were produced with the T-Coffee and HMMer [46,48] using default parameters, slightly refined manually and viewed with the Belvu program [78]. Dendrogram were calculated with the neighbor-join- ing method [79] using ClustalW [80] and was edited with Treetool [81]. The stability of different branches with respect to different choices of subsets of residue positions was checked by bootstrapping experiments (1000 repli- cates) [82]. For profile-profile comparison we used HHpred software (version 1.2.0) downloaded from the authors [49]. Global HMM profiles were done for each family (PRC1 Ring and WDR48-p80) and subfamily (Bmi1/Mel18 and Ring1A/B) using non-redundant align- ments of the RAWUL domain (90% of sequence identity) and removing gappy columns (>70%). We include these profiles into the pdb70 HMM-database [49] before pro- file-profile searches were done. All the profile-profile comparisons were done using default parameters and without known (at Ubl family) or predicted secondary structure information (hhsearch option – ssm 0). Protein-structure predictions and modeling Secondary-structure predictions were performed with Pre- dict Protein server [55]. Fold-recognition analyses were performed with mGenThreader [56]. We generated struc- tural models using Modeler [83] based on pdb structure 1gnu[84]. Models were evaluated using statistical mean force potential [53]. The figure of the model was gener- ated with Pymol program [85]. Authors' contributions LSP carried out the database search, sequence analysis and drafted the manuscript. DD carried out the protein struc- ture prediction and modelling, and helped to draft the manuscript. ZRS participated in the coordination and helped to draft the manuscript. MC conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Page 8 of 11 (page number not for citation purposes)