2 domains with the B30. 2 domains present in a subset of Sorafenib B-Raf NLR proteins recently described in the zebrafish. NLR proteins, also known as CATERPILLER, NACHT or NOD LRR proteins, are large cytoplasmic pro teins involved in inflammation and apoptosis. They are characterized by a NACHT domain and a leucine rich repeat region at the C terminus and vary in their N terminal effector domain, which is a CARD, pyrin or TIR domain. As for TRIM proteins, the physiological functions of NLRs are diverse, and several NLRs are inhibitorsacti vators of the inflammatory and immune responses. For example, NALP3cryopyrin is a key component of the inflammasome and inhibits TNF and TRAF6 induced NF?B activation, while NOD2 plays a role in Inhibitors,Modulators,Libraries NF?B activation.

Large groups of novel, fish specific Inhibitors,Modulators,Libraries NLR proteins have been recently described in fish and appear to be highly related within each species, indicating recent species specific expansions. Some of these teleost NLR proteins contain the NACHT and LRR domains at the C terminus in combination with a B30. 2 domains, as the NLR C described in. The close relatedness Inhibitors,Modulators,Libraries of these B30. 2 domains to the group A finTRIM B30. 2 domain suggests Inhibitors,Modulators,Libraries that the corresponding exon have been sub jected to shuffling between NLR and group A finTRIM, that is, during ftr evolution. The exchange of a ligand recognition module evolving under positive selec tion with another protein family mainly involved in inflammation, immune regulation and possibly pathogen sensing constitutes another argument supporting an immune function for group A finTRIMs.

Phylogenetic analyses suggest that ftr appeared and diversified during the teleost evolution while trim162539 are more ancient genes common to all vertebrates The fintrims and their relatives fol lowed different evolutionary pathways. Both teleosts and mammals possess single orthologous trim25 and trim16, as evidenced Inhibitors,Modulators,Libraries by phylogenetic analysis and conserved synteny. Sequences coding for partial trim16 and trim25 were also identified in the elephant shark genome, confirming that these genes were already present in the early vertebrates. In contrast, fintrims seem to be unique to teleost fish and could not be found in any other group of animals. Since they were present in all fish for which a significant amount of genomic data was availa ble, fintrims most probably appeared during the early evo lution of teleosts.

While they are represented Sirolimus by large gene sets in zebrafish, salmonids and medaka, several fish spe cies such as fugu or stickleback only possess a few copies of fintrim genes. Thus, fintrim genes have been probably subjected to paralleland independentduplication events in the different branches of teleosts. This hypothe sis is strengthened by the fact that zebrafish ftr genes were generally most similar to their immediate neighbors, sug gesting tandem duplication within clusters rather than en bloc duplication as the main gene amplification mecha nism.