Salmonella enterica serovar Typhimurium (S. Typhimurium) is a food-borne pathogen that causes severe gastroenteritis. The ability of Salmonella to cause disease depends on two type III secretion systems (T3SS) encoded in two distinct Salmonella pathogenicity islands, 1 and 2 (SPI1 and SPI2). S. Typhimurium encodes a solo LuxR homolog, SdiA, which can detect the acyl-homoserine lactones (AHLs) produced by other bacteria, and up-regulate the rck operon and the srgE gene. SrgE is predicted to encode a protein of 488 residues with a coiled-coil domain between residues 345 and 382. In silico studies have provided conflicting predictions as to whether SrgE is a T3SS substrate. Therefore, in this work we tested the hypothesis that SrgE is a T3SS effector using two methods, a β-lactamase activity assay and a split GFP complementation assay. Fusions of β-lactamase to residues 40, 100, 150, or 300 were indeed expressed and translocated into host cells, but fusions to residues 400 or 488 were not expressed, suggesting interference by the coiled-coil domain. Similarly, a fusion of GFP S11 to residue 300 of SrgE, but not residue 488, was expressed and translocated into host cells. With both systems, translocation into host cells was dependent upon SPI2. A phylogenetic analysis indicated that srgE is found only within Salmonella subspecies enterica. It is found sporadically within both typhoidal and non-typhoidal serovars, although the SrgE protein sequences found within typhoidal serovars tend to cluster separately from those found in non-typhoidal serovars, suggesting functional diversification.