Identification and cloning of TWIK-originated similarity sequence (TOSS): a novel human 2-pore K+ channel principal subunit

We have identified and cloned a new member of the mammalian tandem pore dom ain K+ channel subunit family, TWIK-originated similarity sequence, from a human testis cDNA library. The 939 bp open reading frame encodes a 313 amin o acid polypeptide with a calculated Mr of 33.7 kDa. Despite the same predi cted topology, there is a relatively ion sequence homology between TWIK-ori ginated similarity sequence and other members of the mammalian tandem pore domain K+ channel subunit family group, TWIK-originated similarity sequence shares a low (<30%) identity with the other mammalian tandem pore domain K + channel subunit family group members and the highest identity (34%) with TWIK-1 at the amino acid level, Similar low levels of sequence homology exi st between all members of the mammalian tandem pore domain K+ channel subun it family. Potential glycosylation and consensus PKC sites are present, Nor thern analysis revealed species and tissue-specific expression patterns. Ex pression of TWIK-originated similarity sequence is restricted to human panc reas, placenta and heart, while in the mouse, TWIK-originated similarity se quence is expressed in the liver. No functional currents were observed in X enopus laevis oocytes or HEK293T cells, suggesting that TWIK-originated sim ilarity sequence mag be targeted to locations other than the plasma membran e or that TWIK-originated similarity sequence may represent a novel regulat ory mammalian tandem pore domain K+ channel subunit family subunit, (C) 199 9 Federation of European Biochemical Societies.