<unk>  is primarily known for modulating the cardiac and epithelial Kv channel alfa subunit,<unk> .<unk>  and<unk>  form a complex in human ventricular cardiomyocytes that generates the slowly activating K+ current, IKs. Together with the rapidly activating K+ current (IKr), IKs is important for human ventricular repolarization.<unk>  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<unk>  or<unk> .<unk>  slows the activation of<unk>  5-10 fold, increases its unitary conductance 4-fold, eliminates its inactivation, and alters the manner in which<unk>  is regulated by other proteins, lipids and small molecules. The association of<unk>  with<unk>  was discovered 8 years after Takumi and colleagues reported the isolation of a fraction of RNA from rat kidney that, when injected into Xenopus oocytes, produced an unusually slow-activating, voltage-dependent, potassium-selective current. Takumi et al discovered the<unk>  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<unk>  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<unk>  was cloned and found to co-assemble with<unk> , and it was shown that Xenopus laevis oocytes endogenously express<unk> , which is upregulated by exogenous expression of<unk>  to generate the characteristic slowly activating current.,<unk>  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<unk>  or<unk> .<unk>  is also reported to regulate two other KCNQ family α subunits, KCNQ4 and KCNQ5.<unk>  increased both their peak currents in oocyte expression studies, and slowed the activation of the latter.,<unk>  also regulates hERG, which is the Kv α subunit that generates ventricular IKr.<unk>  doubled hERG current when the two were expressed in mammalian cells, although the mechanism for this remains unknown. Although<unk>  had no effect when co-expressed with the Kv1.1 α subunit in Chinese Hamster ovary (CHO) cells,<unk>  traps the N-type (rapidly inactivating) Kv1.4 α subunit in the ER/Golgi when co-expressed with it.<unk>  (and<unk>  also has this effect on the two other canonical N-type Kv α subunits, Kv3.3 and Kv3.4. This appears to be a mechanism for ensuring that homomeric N-type channels do not reach the cell surface, as this mode of suppression by<unk>  or<unk>  is relieved by co-expression of same-subfamily delayed rectifier (slowly inactivating) α subunits. Thus, Kv1.1 rescued Kv1.4, Kv3.1 rescued Kv3.4; in each of these cases the resultant channels at the membrane were heteromers (e.g., Kv3.1-Kv3.4) and displayed intermediate inactivation kinetics to those of either α subunit alone.,<unk>  also regulates the gating kinetics of Kv2.1, Kv3.1 and Kv3.2, in each case slowing their activation and deactivation, and accelerating inactivation of the latter two., No effects were observed upon oocyte co-expression of<unk>  and Kv4.2, but<unk>  was found to slow the gating and increase macroscopic current of Kv4.3 in HEK cells. In contrast, channels formed by Kv4.3 and the cytosolic ancillary subunit KChIP2 exhibited faster activation and altered inactivation when co-expressed with<unk>  in CHO cells. Finally,<unk>  inhibited Kv12.2 in Xenopus oocytes.
KCNE1
MCN
CLCN1
AHDC1
PANO1
TAAR1
SLITRK1
SMN1