HCN2

The protein encoded by this gene is a hyperpolarization-activated cation channel involved in the generation of native pacemaker activity in the heart and in the brain. The encoded protein is activated by cAMP and can produce a fast, large current. Defects in this gene were noted as a possible cause of some forms of epilepsy.

Full Name

hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2

Function

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).

Biological Process

Cell-cell signaling Source: ProtInc
Cellular response to cAMP Source: UniProtKB
Cellular response to cGMP Source: UniProtKB
Membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
Potassium ion import across plasma membrane Source: BHF-UCL
Potassium ion transmembrane transport Source: UniProtKB
Regulation of ion transmembrane transport Source: UniProtKB-KW
Regulation of membrane depolarization Source: ComplexPortal
Regulation of membrane potential Source: UniProtKB
Sodium ion import across plasma membrane Source: BHF-UCL
Sodium ion transmembrane transport Source: UniProtKB

Cellular Location

Cell membrane

Topology

Cytoplasmic: 1-215
Helical: 216-236
Extracellular: 237-240
Helical: 241-261
Cytoplasmic: 262-288
Helical: 289-309
Extracellular: 310-317
Helical: 318-338
Cytoplasmic: 339-369
Helical: 370-390
Extracellular: 391-413
Pore-forming: 414-435
Extracellular: 436-440
Helical: 441-461
Cytoplasmic: 462-889

PTM

Phosphorylation at Ser-668 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating.