Potassium voltage-gated channel subfamily E member 2 (KCNE2), also known as MinK-related peptide 1 (MiRP1), is a protein that in humans is encoded by the KCNE2 gene on chromosome 21. MiRP1 is a voltage-gated potassium channel accessory subunit (beta subunit) associated with Long QT syndrome. It is ubiquitously expressed in many tissues and cell types. Because of this and its ability to regulate multiple different ion channels, KCNE2 exerts considerable influence on a number of cell types and tissues. Human KCNE2 is a member of the five-strong family of human KCNE genes. KCNE proteins contain a single membrane-spanning region, extracellular N-terminal and intracellular C-terminal. KCNE proteins have been widely studied for their roles in the heart and in genetic predisposition to inherited cardiac arrhythmias. The KCNE2 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. More recently, roles for KCNE proteins in a variety of non-cardiac tissues have also been explored. Discovery Steve Goldstein (then at Yale University) used a BLAST search strategy, focusing on KCNE1 sequence stretches known to be important for function, to identify related expressed sequence tags (ESTs) in the NCBI database. Using sequences from these ESTs, KCNE2, 3 and 4 were cloned. Tissue distribution KCNE2 protein is most readily detected in the choroid plexus epithelium, gastric parietal cells, and thyroid epithelial cells. KCNE2 is also expressed in atrial and ventricular cardiomyocytes, the pancreas, pituitary gland, and lung epithelium. In situ hybridization data suggest that KCNE2 transcript may also be expressed in various neuronal populations. Structure Gene The KCNE2 gene resides on chromosome 21 at the band 21q22.11 and contains 2 exons. Since human KCNE2 is located ~79 kb from KCNE1 and in the opposite direction, KCNE2 is proposed to originate from a gene duplication event. Protein This protein belongs to the potassium channel KCNE family and is one five single transmembrane domain voltage-gated potassium (Kv) channel ancillary subunits. KCNE2 is composed of three major domains: the N-terminal domain, the transmembrane domain, and the C-terminal domain. The N-terminal domain protrudes out of the extracellular side of the cell membrane and is, thus, soluble in the aqueous environment. Meanwhile, the transmembrane and C-terminal domains are lipid-soluble to enable the protein to incorporate into the cell membrane. The C-terminal faces the intracellular side of the membrane and may share a putative PKC phosphorylation site with other KCNE proteins. Like other KCNEs, KCNE2 forms