SirA functions as a response regulator as part of a two-component system, where BarA is the sensor kinase. This system increases the expression of virulence genes and decreases the expression of motility genes . BarA phosphorylates SirA, thereby activating the protein. Phosphorylated SirA directly activates virulence expression by interacting with hilA and hilC promoters, while repressing the flagellar regulon indirectly by binding to the csrB promoter, which in turn affects flagellar gene expression. Orthologues of SirA from Salmonella spp. can be found throughout proteobacteria, such as GacA in Psuedomonas spp., VarA in Vibrio cholerae, ExpA in Erwinia carotovora, LetA in Legionella pneumophila, and UvrY in Escherichia coli . A sensor kinase for SirA is present in each of these organisms as well; the sensor kinase is known as BarA in E. coli and Salmonella spp., but has different names in other genera. In different species, SirA/BarA orthologues are required for virulence gene expression, exoenzyme and antibiotic production, motility, and biofilm formation.
The structure of SirA consists of an alpha/beta sandwich with a beta-alpha-beta-alpha-beta(2) fold, comprising a mixed four-stranded beta-sheet stacked against two alpha-helices, both of which are nearly parallel to the strands of the beta-sheet .
Several uncharacterised bacterial proteins (73 to 81 amino-acid residues in length) that contain a well-conserved region in their N-terminal region show structural similarity to the SirA protein, including the E. coli protein YedF, and other members of the UPF0033 family.