Edema factor (EF), which constitutes one of the three proteins composing the anthrax toxin, causes edema in the host (PubMed:6285339, PubMed:2108958, PubMed:11807546). Acts as a calmodulin-dependent adenylyl cyclase by converting ATP to cAMP, leading to dramatic elevation of intracellular cAMP levels in the host, thereby causing edema (PubMed:6285339, PubMed:2108958, PubMed:11807546). EF is not toxic by itself and only acts as a edema factor when associated with protective antigen (PA) to form the edema toxin (EdTx) (PubMed:11553601, PubMed:2108958). Required for the survival of germinated spores within macrophages at the early stages of infection (PubMed:11737637). ATP = 3',5'-cyclic AMP + diphosphate Host calmodulin is an absolute requirement for its activation (PubMed:2114169, PubMed:11807546). Inhibited by ethyl 5-aminopyrazolo[1,5-a]quinazoline-3-carboxylate (PubMed:12676933). Interacts (via ATLF domain) with the cleaved form of protective antigen (PA-63) anthrax toxin; interaction is required for EF translocation into the host cytoplasm. Translocation into host cytosol is mediated via interaction with the cleaved form of protective antigen (PA-63): following secretion, EF binds via its N-terminal region to the upper rim of the ring-shaped homooligomer (homoheptamer or homooctamer) formed by PA-63 on the host cell membrane (PubMed:32047164). In this PA-63 pre-pore state, the N-terminal segment of EF refolds into an alpha helix engaged in the alpha-clamp of the PA-63 pre-pore (PubMed:32047164, PubMed:32521227). Recruitment to the PA-63 pre-pore enables domain reorganization of EF (PubMed:32521227). Loaded complexes are then endocytosed, followed by a conformational change of oligomerized PA-63 from the pre-pore to pore state, which is triggered by the low pH in the endosome (PubMed:11207582). EF is then unfolded to pass through the PA-63 pore and translocate into the host cytosol (PubMed:32047164). The N-terminal region contains the ATLF domain responsible for binding to the cleaved form of protective antigen (PA-63) (PubMed:11807546). The C-terminal region contains the calmodulin-dependent activation domain and the catalytic site (PubMed:11807546). This region is composed of three globular domains: CA, CB and a helical domain connected to CA by a linker (PubMed:11807546). The active site lies at the interface of CA and CB (PubMed:11807546). The metal ion is coordinated by residues from CA; calmodulin probably binds in a multistep fashion first to residues in CA and then to residues present in the linker and the helical domain (PubMed:11807546). Belongs to the adenylyl cyclase class-2 family.