HERG (human eag-related gene) encodes an inward-rectifier potassium channel 
formed by the assembly of four subunits. Since the truncated HERG protein in 
patients with long QT syndrome induces a dominant phenotype, that is, cardiac 
sudden death, the assembly of nonfunctional complexes between wild-type and 
mutated subunits was implicated in causing the disease. To understand 
HERG-mediated cardiac sudden death at the molecular level, it is important to 
determine which regions in the HERG protein participate in subunit interaction. 
We therefore report the identification of a subunit interaction domain, 
NAB(HERG), that is localized at the hydrophilic cytoplasmic N terminus and can 
form a tetramer in the absence of the rest of the HERG protein. Truncated HERG 
proteins containing NAB(HERG), including one that resulted from the delta1261 
human mutation, inhibit the functional expression of the HERG channel in 
transfected cells. Together, these results support the notion that the 
expression of HERG in the human heart may be decreased in the presence of the 
truncated subunit. Such a decrease of potassium channel expression can 
contribute to the longer QT intervals observed in the patients with the HERG 
mutation.