K+/Na+ hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4)

Function: - hyperpolarization-activated ion channel with very slow activation & inactivation - exhibits weak selectivity for K⁺ over Na⁺ - may contribute to the native pacemaker currents in heart (If) & in neurons (Ih) - activated by cAMP - may mediate responses to sour stimuli - the K⁺ channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits Structure: - the segment S4 is probably the voltage-sensor & is characterized by a series of positively charged amino acids at every third position - belongs to the K⁺ channel HCN family - contains 1 cyclic nucleotide-binding domain Compartment: membrane Expression: - highly expressed in thalamus, testis & in heart, both in ventricle & atrium - detected at much lower levels in amygdala, substantia nigra, cerebellum & hippocampus Pathology: - defects in HCN4 are a cause of sick sinus syndrome type 2 - defects in HCN4 are the cause of Brugada syndrome type 8 Notes: - inhibited by extracellular Cs+

General

hyperpolarization-activated cyclic nucleotide gated K+ channel phosphoprotein transmembrane 6 protein

Properties

SIZE: entity length = 1203 aa MW = 129 kD COMPARTMENT: plasma membrane MOTIF: cytoplasmic domain {1-266} MOTIF: Involved in subunit assembly {209-260} transmembrane domain {267-287} exoplasmic loop {288-293} transmembrane domain {294-314} cytoplasmic loop {315-340} transmembrane domain {341-361} exoplasmic loop {362-368} transmembrane domain {369-389} cytoplasmic loop {390-420} transmembrane domain {421-441} exoplasmic loop {442-496} MOTIF: N-glycosylation site {N458} H5 (K+) pore-forming region {465-486} transmembrane domain {497-517} cytoplasmic domain {518-1203} MOTIF: cAMP-binding site SITE: 595-710 proline-rich region SITE: 924-1076 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S935} ION-PERMEABILITY: K+

Database Correlations

OMIM correlations MORBIDMAP 605206 UniProt Q9Y3Q4 PFAM correlations Entrez Gene 10021 Kegg hsa:10021