InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HCN4

Summary

InnateDB Protein

IDBP-21088.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HCN4

Protein Name

hyperpolarization activated cyclic nucleotide-gated potassium channel 4

Synonyms

SSS2;

Species

Homo sapiens

Ensembl Protein

ENSP00000261917

InnateDB Gene

IDBG-21086 (HCN4)

Protein Structure

UniProt Annotation

Function

Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli. {ECO:0000269PubMed:10228147, ECO:0000269PubMed:10430953, ECO:0000269PubMed:16407510, ECO:0000269PubMed:19165230, ECO:0000269PubMed:20829353}.

Subcellular Localization

Cell membrane {ECO:0000269PubMed:10228147, ECO:0000269PubMed:10430953, ECO:0000269PubMed:16407510}; Multi- pass membrane protein {ECO:0000269PubMed:10228147, ECO:0000269PubMed:10430953, ECO:0000269PubMed:16407510}.

Disease Associations

Sick sinus syndrome 2 (SSS2) [MIM:163800]: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth. {ECO:0000269PubMed:16407510, ECO:0000269PubMed:20662977}. Note=The disease is caused by mutations affecting the gene represented in this entry.Brugada syndrome 8 (BRGDA8) [MIM:613123]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269PubMed:19165230}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Highly expressed in thalamus, testis and in heart, both in ventricle and atrium. Detected at much lower levels in amygdala, substantia nigra, cerebellum and hippocampus. {ECO:0000269PubMed:10228147, ECO:0000269PubMed:10430953}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005216	ion channel activity
GO:0005222	intracellular cAMP activated cation channel activity
GO:0005248	voltage-gated sodium channel activity
GO:0005249	voltage-gated potassium channel activity
GO:0005261	cation channel activity
GO:0005515	protein binding
GO:0030552	cAMP binding
GO:0042802	identical protein binding

Biological Process

GO:0001701	in utero embryonic development
GO:0002027	regulation of heart rate
GO:0006811	ion transport
GO:0006812	cation transport
GO:0006936	muscle contraction
GO:0007268	synaptic transmission
GO:0008015	blood circulation
GO:0008016	regulation of heart contraction
GO:0034765	regulation of ion transmembrane transport
GO:0035725	sodium ion transmembrane transport
GO:0042391	regulation of membrane potential
GO:0055085	transmembrane transport
GO:0071320	cellular response to cAMP
GO:0071321	cellular response to cGMP
GO:0071805	potassium ion transmembrane transport

Cellular Component

GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0016020	membrane
GO:0031226	intrinsic component of plasma membrane
GO:0043195	terminal bouton

Protein Structure and Domains

PDB ID

InterPro

IPR000595 Cyclic nucleotide-binding domain
IPR003938 Potassium channel, voltage-dependent, EAG/ELK/ERG
IPR005821 Ion transport domain
IPR013621 Ion transport N-terminal
IPR018490 Cyclic nucleotide-binding-like

PFAM

PF00027
PF00520
PF08412

PRINTS

PR01463

PIRSF

SMART

SM00100

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt