Hyperpolarization-activated, cyclic nucleotide-binding channels (HCN) are voltage-gated cation channels that are activated by direct binding of intracellular cyclic nucleotides. The HCN family consists of four members (HCN1–4), each with a core transmembrane segment domain and a carboxy-terminal 120 amino-acid cyclic nucleotide-binding domain motif (1). HCN channels are expressed in the brain, heart, thalamus and testis (1). The pacemaker properties of HCN channels contribute to spontaneous rhythmic activity in the brain and heart (1). The genes encoding human HCN1 and HCN2 map to chromosomes 5 and 19p13.3, respectively (2,3). The genes encoding HCN3 and HCN4 map to chromosomes 1q21.3 and 15q24-q25, respectively (4,5).
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). Produces a large instantaneous current. Activated by cAMP. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.
Subunit:
The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits. Heteromultimer with HCN1. Interacts with KCNE2.
Subcellular Location:
Membrane; Multi-pass membrane protein.
Tissue Specificity:
Highly expressed throughout the brain. Detected at low levels in heart.
Similarity:
Belongs to the potassium channel HCN family.
Contains 1 cyclic nucleotide-binding domain.
SWISS:
Q9UL51
Gene ID:
610
Database links:
Entrez Gene: 610 Human
Entrez Gene: 15166 Mouse
Entrez Gene: 114244 Rat
Omim: 602781 Human
SwissProt: Q9UL51 Human
SwissProt: O88703 Mouse
SwissProt: Q9JKA9 Rat
Unigene: 124161 Human
Unigene: 12956 Mouse
Unigene: 224995 Rat
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