This gene is of note due to the recent identification of activating mutations in the alpha2-chimaerin gene in patients with familial Duane syndrome. Activating mutations in alpha2-chimaerin, a Rac-GAP, might correspond to decreased expression of DEPDC2, a Rac-GEF. Decreased expression of both CPA6 and DEPDC2 might produce a cumulative effect resulting in a Duane syndrome-like phenotype. While this appears to be an excellent hypothesis, knockdown of the DEPDC2 gene along with CPA6 in the zebrafish, using specific splice-blocking morpholinos, did not result in any noticeable defects in eye abduction. Gram-negative bacteria use various secretion systems to transport proteins across bacterial membranes. To date, at least seven secretion systems are known in Gram-negative bacteria. The type VI secretion system is a recently discovered protein transport RO5185426 complex which contributes to bacterial pathogenesis. T6SS was initially identified in Vibrio cholerae and named IcmF associated homologous protein cluster. In 2006, Mekalanos group showed that the IAHP gene clusters of V. cholerae and Pseudomonas aeruginosa were involved in protein secretion and Pukatzki et al., renamed this novel secretion system as T6SS. T6SSs are present in animal and plant proteobacteria and play an important role in the virulence of many human and animal pathogens. In silico analyses showed that T6SSs are found in at least 92 bacterial genomes and can be divided into four to five different phylogenetic groups. Hallmarks of T6SSs include the presence of an ortholog of IcmF, an AAA + ATPase and at least two secreted proteins, namely hemolysin co-regulated protein and valine glycine repeat protein. Hcp homologs are secreted through a functional T6SS, and act as virulence factors in pathogens such as P. aeruginosa, V. cholerae, and Edwardsiella tarda. Hcp1 in P. aeruginosa is actively secreted in lungs of infected cystic fibrosis patients and is likely to contribute to pathogenesis. The crystal structure of Hcp1 from P. aeruginosa revealed that it can associate into hexameric rings that stack onto each other to form a nanotube-like channel. Another common virulence factor secreted by T6SS is VgrG. It has a trimeric phage tail spike like structure similar to that of the T4 phage gp5-gp27 complex. It is proposed that the VgrG protein might act as a membrane-puncturing device to help deliver effectors into host cells. E. tarda is a Gram-negative pathogen which is associated with septicemia and fatal infections in a wide variety of animals including fish and humans. In humans, it causes gastroand extra-intestinal infections such as myonecrosis, bacteremia, septic arthritis and wound infections. Using a comparative proteomics approach, we have previously identified two secretion systems, namely type III secretion system and T6SS, from a fish isolate PPD130/91. In this work, we focus on eliciting the secretion property of EvpC from structural and functional aspects. Here we report the crystal structure of EvpC at 2.8 A ˚ resolution and studies on its oligomerization and secretion.