Recombinant Human G protein-activated inward rectifier potassium channel 4 (KCNJ5) Protein

Function

Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium. This potassium channel is controlled by G proteins

Subcellular Location

Membrane (Multi-pass membrane protein)

Disease Association

Long QT syndrome 13 (LQT13) : A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. [The disease is caused by variants affecting the gene represented in this entry] | Hyperaldosteronism, familial, 3 (HALD3) : A form of hyperaldosteronism characterized by hypertension secondary to massive adrenal mineralocorticoid production. HALD3 patients present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. Hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension. [The disease is caused by variants affecting the gene represented in this entry] | [Somatic mutations in KCNJ5 have been found in aldosterone-producing adrenal adenomas and can be responsible for aldosteronism associated with cell autonomous proliferation. APAs are typically solitary, well circumscribed tumors diagnosed between ages 30 and 70. They come to medical attention due to new or worsening hypertension, often with hypokalemia. The precise role of KCNJ5 mutations in APA is under debate. They produce increased sodium conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium entry, the signal for aldosterone production and cell proliferation. However, they may not be causative of APA development but may be a consequence of tumorigenesis, playing only a contributory role toward aldosterone overproduction and tumor growth (PubMed:22275527). Somatic mutations in KCNJ5 have not been found in non-aldosterone secreting adrenal adenomas suggesting that they are specifically associated with APA (PubMed:22275527, PubMed:22848660)] | [Mutations in KCNJ5 are involved in the pathogenesis of hypertension without primary aldosteronism but with increased aldosterone response to ACTH stimulation]

Tissue Specificity

Islets, exocrine pancreas and heart. Expressed in the adrenal cortex, particularly the zona glomerulosa

Subunit

Associates with KCNJ3/GIRK1 to form a G protein-activated heteromultimer pore-forming unit. The resulting inward current is much larger (PubMed:8868049, PubMed:10659995, PubMed:8558261). Associates with KCNJ6/GIRK2 to form a G protein-activated heteromultimer pore-forming unit (By similarity)

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• Taylor T.D. et al. Human chromosome 11 DNA sequence and analysis including novel gene identification. — Nature (2006)