Cotranslational protein transport to the endoplasmic reticulum is controlled by the concerted interaction of three GTPases: the SRP54 subunit of the signal recognition particle (SRP) and the α- and β-subunits of the SRP receptor (SR). SRβ is related to ADP-ribosylation factor (ARF)-type GTPases, and the recently published crystal structure of SRβ-GTP in complex with the binding domain of SRα suggested that SRβ, like all ARF-type GT-Pases, requires a guanine nucleotide exchange factor (GEF) for function. Searching the sequence data base, we identified significant sequence similarity between the Sec7 domain of ARF-GEFs and the cytosolic domains of the β-subunits of the two homologous heterotrimeric protein-conducting channels in yeast. Using a fluorescence nucleotide exchange assay, we show that the β-subunits of the heterotrimeric protein-conducting channels function as the GEFs for SRβ. Both the cytosolic domain of Sec61β as well as the holo-Sec61β, when part of the isolated trimeric Sec61p complex, function as the GEF for SRβ, whereas the same Sec61β, when part of the heptameric complex that facilitates posttranslational protein transport, is inactive as the GEF for SRβ.