Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

UniProt Q9Y3Q4 Organism Homo sapiens Gene HCN4

Also known as: HCN4

Function

Hyperpolarization-activated ion channel that are permeable to Na(+) and K(+) ions with very slow activation and inactivation. Exhibits higher selectivity for K(+) over Na(+) ions. Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat (Probable). Contributes to the native pacemaker currents in neurons (Ih) (Probable). May mediate responses to sour stimuli (By similarity).

Classification

Family (Pfam): PF00027 cNMP_binding, PF00520 Ion_trans, PF08412 Ion_trans_N
InterPro: cNMP-bd_CS, cNMP-bd_dom, cNMP-bd_dom_sf, Ion_trans_dom, Ion_trans_N, K/Na_HCN_channel, K_chnl_volt-dep_EAG/ELK/ERG, RmlC-like_jellyroll
Functional cluster: RNA-Polymerase II Transcription Factors

Experimental structures · PDB · 8

2MNG NMR
3OTF X-ray 2.40A
3U11 X-ray 2.50A
4HBN X-ray 2.60A
4KL1 X-ray 2.70A
4NVP X-ray 2.50A
6GYN EM 3.40A
6GYO EM 3.40A

A predicted model is available from AlphaFold.

Gene Ontology · 30

Disease associations

sick sinus syndrome 2, autosomal dominant MONDO:0008102
Brugada syndrome 8 MONDO:0013148
epilepsy, idiopathic generalized, susceptibility to, 18 MONDO:0030434

Drugs targeting this protein · 3

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 3 shared papers
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 2 shared papers
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 1 shared papers
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 1 shared papers

Literature · 14 cited papers

A loss-of-function HCN4 mutation associated with familial benign myoclonic epilepsy in infancy causes increased neuronal excitability. Front. Mol. Neurosci. · 2018
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels contain multiple S-palmitoylation sites. J. Physiol. Sci. · 2016
Cyclic dinucleotides bind the C-linker of HCN4 to control channel cAMP responsiveness. Nat. Chem. Biol. · 2014
Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel. Structure · 2012
Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels. J. Biol. Chem. · 2011
Structural basis for the cAMP-dependent gating in the human HCN4 channel. J. Biol. Chem. · 2010
A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews. J. Cardiovasc. Electrophysiol. · 2010
Role of HCN4 channel in preventing ventricular arrhythmia. J. Hum. Genet. · 2009
Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. N. Engl. J. Med. · 2006
Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J. Biol. Chem. · 2004
Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels. J. Biol. Chem. · 2003
… and 2 more in the literature graph

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