Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity). Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Heterotetramer with HCN1. Forms an obligate 4:4 complex with accessory subunit PEX5L. Interacts with KCNE2 (By similarity). Homotetramer. Highly expressed throughout the brain. Detected at low levels in heart. The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Phosphorylation at Ser-668 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating. Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Inhibited by extracellular cesium ions. Belongs to the potassium channel HCN family.