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HCN4 Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) and in neurons (Ih). Activated by cAMP. May mediate responses to sour stimuli. Defects in HCN4 are a cause of sick sinus syndrome type 2 (SSS2); also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors, in which case it is considered to be a congenital disorder. Defects in HCN4 are the cause of Brugada syndrome type 8 (BRGDA8). A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset. Belongs to the potassium channel HCN family. Note: This description may include information from UniProtKB.
Protein type: Channel, cation; Membrane protein, integral; Membrane protein, multi-pass
Chromosomal Location of Human Ortholog: 15q24.1
Cellular Component: intrinsic component of plasma membrane; perinuclear region of cytoplasm; plasma membrane
Molecular Function: cAMP binding; identical protein binding; intracellular cAMP activated cation channel activity; voltage-gated potassium channel activity; voltage-gated sodium channel activity
Biological Process: blood circulation; cation transport; muscle contraction; regulation of heart rate; regulation of membrane potential; regulation of postsynaptic membrane potential
Disease: Brugada Syndrome 8; Sick Sinus Syndrome 2, Autosomal Dominant
Reference #:  Q9Y3Q4 (UniProtKB)
Alt. Names/Synonyms: HCN4; hyperpolarization activated cyclic nucleotide-gated cation channel 4; hyperpolarization activated cyclic nucleotide-gated potassium channel 4; Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4; SSS2
Gene Symbols: HCN4
Molecular weight: 129,042 Da
Basal Isoelectric point: 9.07  Predict pI for various phosphorylation states
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Protein Structure Not Found.
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