cDNA clones encoding a novel activin beta subunit have been isolated from mouse liver cDNA library. An amino acid homology comparison among members of the TGF-beta superfamily indicates that the open reading frame codes for a new activin/inhibin beta subunit. The predicted mature region of the subunit shows > 60% identity with activin beta C and beta D and > or = 45% identity with activin beta A and beta B, but only 20-40% amino acid sequence identity with other TGF-beta superfamily members. Therefore, the novel subunit has been designated activin beta E. Alignment of the mature growth factor region of the five activin beta subunits revealed that activin beta A and beta B share 63% amino acid identity, while activin beta C, beta D, and beta E share 62% identity. Therefore, activin beta A and beta B are most related to one another, while activin beta C, beta D, and beta E may represent a subset of related sequences.