BMC Genomics 2008, 9:308 http://www.biomedcentral.com/1471-2164/9/308 (PDB:1aar) as K29, K48, and K63). Hence, it appears unlikely that this domain functions as a traditional UBL modifier. PRC1 Ring finger and WDR48-p80 proteins therefore could be included in the group of UDPs. There are two classes of UDPs as well [63] differentiated by their location and sequence similarity to ubiquitin of their Ubq-like domains. The Ubq-like domain (UBD) proteins have the Ubq-like domain located at or close to the N-terminus of the pro- tein and defined by a stretch of 45–80 residues with sig- nificant sequence homology to ubiquitin, while the Ubiquitin regulatory X (UBX) domain proteins have the Ubq-like domain at the C-terminus consisting of ~80 amino acids that shares common secondary structure organization with ubiquitin despite the lack of significant sequence homology [64,65]. The UBD proteins have been shown to bind to ubiquitin-interacting motifs (UIMs), like parkin protein. Defective parkin protein is responsi- ble for a common familial form of Parkinson's disease. Parkin encodes an E3 ubiquitin ligase that contains two Ring finger domains at its C-terminus and one Ubq-like domain at its N-terminus [65,66]. Binding of the parkin ubiquitin-like domain to the Eps15 UIM is required for parkin-mediated Eps15 ubiquitination [66]. Conversely, only very few UBX domain proteins have been studied in detail and no general function for the UBX domain has yet emerged. Most of the UBX domain pro- teins identified so far can be grouped into four evolution- ary conserved protein families represented by the human Fas-associated factor-1 (FAF1), p47, Y33K, and Rep8 pro- teins [67]. Recent reports showed that the UBX domains may act as general binding modules for p97 and/or p97 homologs, possibly representing a first common role for UBX domains [68]. RAWUL domain seems to fall into the UBX domain protein family since it is located at the C-ter- minus, comprise about 80 residues and the conserved hydrophobic core of the Ubq fold. However, as far as we know, UBX domains have not been found together with a Ring finger domain or a WD40 repeat domain. In the case of the poorly characterized WDR48-p80 family [50-52], the association of WD40 repeats and RAWUL domain could point out to a E3-ligase related function, since WD40 repeats containing proteins are commonly implicated in protein-protein interaction [69] and these repeats have been recently described as key elements in E3 ubiquitin ligase complexes [70]. On the other side, our analysis revealed that the combina- tion of a Ring finger domain at the N-terminus and a RAWUL domain at the C-terminus is a key feature to define the PRC1 Ring finger protein family, since no other protein presents this domain architecture. The Ring finger domains of the Ring (Ring1A and 1B) and Bmi1 proteins are responsible for the E3 ubiquitin ligase activity [33,34], whereas the region corresponding to the RAWUL domain has been shown to mediate protein-protein interaction with Pc and Ph [38-40]. The identification of an Ubq-like domain in this region raise the possibility that these inter- actions could be establish through a yet uncharacterised UIM present in Pc and Ph. However, due to the structural similarities between the RAWUL domain and ubiquitin, it is also possible that RAWUL could act as an auto-inhibi- tory domain, by direct competition with the substrate, regulating specificities and/or ubiquitination capabilities of the E3 ligase complex, as previously suggested for Ubq- like domains fused to ubiquitin-specific proteases [71], or as a bridge, linking the proteasome and histone post- translational modifications, as suggested for the Ubq-like domain in the Ubiquitin plant homeodomain Ring finger (UHRF) protein family [72]. Identification of plant and worm PRC1 Ring finger protein orthologs In the course of characterizing the PRC1 Ring finger pro- teins, we identified a set of proteins in Arabidopsis, Oryza sativa, Vitis vinifera and worms that share the PRC1 ring finger domain architecture, an N-terminal Ring finger domain and a RAWUL domain at their C-terminal region (Figure 1, 3 and 4). The preservation of domain architec- ture among these proteins indicates that these plant and worm proteins are potential orthologs of animal PRC1 Ring finger proteins. The Ring finger domain is highly abundant in plant pro- teins, with as many as 469 predicted Ring finger-contain- ing proteins in the Arabidopsis genome [73]. The large number of potential Ring finger proteins in Arabidopsis suggests that target specific ubiquitination plays an important role in protein regulation in plants. However, the combination of the Ring finger domain and the RAWUL domain, which is a specific feature of the PRC1 Ring finger proteins, is found in only a few plant proteins. In Arabidopsis, there are four PRC1 Ring finger genes, At1g03770, At5g44280, At2g30580 and At3g23060 that codify the predicted proteins Q0WX00, estQ9FKW0, Q94AY3 and Q9LS86, respectively. There are full length cDNAs for these four genes with one open reading frame predicted for each (the Arabidopsis information resource (TAIR) database [74]. Online microarray expression data proof that these genes are expressed [74]. Outside of these two domains, the plant proteins have diverged significantly from their putative animal counter- parts (Figure 4), but usually PcG protein orthologs do not display sequence homology outside the conserved domains, not only in evolutionary distant organisms but also among paralogs in a given organism [75]. Taking into Page 6 of 11 (page number not for citation purposes)