ID:HCN4_HUMAN DESCRIPTION: RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4; FUNCTION: 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. SUBUNIT: The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits. SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Highly expressed in thalamus, testis and in heart, both in ventricle and atrium. Detected at much lower levels in amygdala, substantia nigra, cerebellum and hippocampus. DOMAIN: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. DISEASE: Defects in HCN4 are a cause of sick sinus syndrome type 2 (SSS2) [MIM:163800]; 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. DISEASE: Defects in HCN4 are the cause of Brugada syndrome type 8 (BRGDA8) [MIM:613123]. 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. MISCELLANEOUS: Inhibited by extracellular cesium ions. SIMILARITY: Belongs to the potassium channel HCN family. SIMILARITY: Contains 1 cyclic nucleotide-binding domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y3Q4
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002027 regulation of heart rate GO:0003254 regulation of membrane depolarization GO:0006811 ion transport GO:0006812 cation transport GO:0006813 potassium ion transport GO:0006814 sodium ion transport GO:0006936 muscle contraction GO:0008015 blood circulation GO:0034765 regulation of ion transmembrane transport GO:0035725 sodium ion transmembrane transport GO:0042391 regulation of membrane potential GO:0055085 transmembrane transport GO:0055117 regulation of cardiac muscle contraction GO:0071320 cellular response to cAMP GO:0071321 cellular response to cGMP GO:0071805 potassium ion transmembrane transport GO:0086012 membrane depolarization during cardiac muscle cell action potential GO:0086015 SA node cell action potential GO:0086046 membrane depolarization during SA node cell action potential GO:0086091 regulation of heart rate by cardiac conduction GO:0098719 sodium ion import across plasma membrane GO:0098909 regulation of cardiac muscle cell action potential involved in regulation of contraction GO:1990573 potassium ion import across plasma membrane
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
