 Takumi "et al" discovered the KCNE1 gene and it was correctly predicted to encode a single-transmembrane domain protein with an extracellular N-terminal domain and a cytosolic C-terminal domain.The ability of KCNE1 to generate this current was confusing because of its simple primary structure and topology, contrasting with the 6-transmembrane domain topology of other known Kv α subunits such as "Shaker" from "Drosophila", cloned 2 years earlier.The mystery was solved when KCNQ1 was cloned and found to co-assemble with KCNE1, and it was shown that "Xenopus laevis" oocytes endogenously express KCNQ1, which is upregulated by exogenous expression of KCNE1 to generate the characteristic slowly activating current., KCNQ1 is also essential for the normal function of many different epithelial tissues, but in these non-excitable cells it is thought to be predominantly regulated by KCNE2 or KCNE3.