InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SCN5A

Summary

InnateDB Protein

IDBP-372411.5

Last Modified

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

Gene Symbol

SCN5A

Protein Name

sodium channel, voltage-gated, type V, alpha subunit

Synonyms

CDCD2; CMD1E; CMPD2; HB1; HB2; HBBD; HH1; ICCD; IVF; LQT3; Nav1.5; PFHB1; SSS1; VF1;

Species

Homo sapiens

Ensembl Protein

ENSP00000398266

InnateDB Gene

IDBG-26059 (SCN5A)

Protein Structure

UniProt Annotation

Function

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels. {ECO:0000269PubMed:19074138}.

Subcellular Localization

Membrane {ECO:0000269PubMed:19074138}; Multi-pass membrane protein {ECO:0000269PubMed:19074138}.

Disease Associations

Progressive familial heart block 1A (PFHB1A) [MIM:113900]: A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His- Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death. {ECO:0000269PubMed:12569159, ECO:0000269PubMed:12574143, ECO:0000269PubMed:19251209}. Note=The disease is caused by mutations affecting the gene represented in this entry.Long QT syndrome 3 (LQT3) [MIM:603830]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. {ECO:0000269PubMed:10377081, ECO:0000269PubMed:10508990, ECO:0000269PubMed:10627139, ECO:0000269PubMed:10911008, ECO:0000269PubMed:10973849, ECO:0000269PubMed:11304498, ECO:0000269PubMed:11997281, ECO:0000269PubMed:12209021, ECO:0000269PubMed:12673799, ECO:0000269PubMed:15840476, ECO:0000269PubMed:16922724, ECO:0000269PubMed:18060054, ECO:0000269PubMed:18708744, ECO:0000269PubMed:18848812, ECO:0000269PubMed:18929331, ECO:0000269PubMed:7651517, ECO:0000269PubMed:7889574, ECO:0000269PubMed:8541846, ECO:0000269PubMed:9506831, ECO:0000269PubMed:9686753, ECO:0000269Ref.30}. Note=The disease is caused by mutations affecting the gene represented in this entry.Brugada syndrome 1 (BRGDA1) [MIM:601144]: 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:11748104, ECO:0000269PubMed:11901046, ECO:0000269PubMed:12051963, ECO:0000269PubMed:12106943, ECO:0000269PubMed:15023552, ECO:0000269PubMed:15338453, ECO:0000269PubMed:15579534, ECO:0000269PubMed:15851320, ECO:0000269PubMed:16266370, ECO:0000269PubMed:16325048, ECO:0000269PubMed:16616735, ECO:0000269PubMed:17075016, ECO:0000269PubMed:17081365, ECO:0000269PubMed:17198989, ECO:0000269PubMed:18252757, ECO:0000269PubMed:18341814, ECO:0000269PubMed:18451998, ECO:0000269PubMed:18456723, ECO:0000269PubMed:18616619, ECO:0000269PubMed:19251209, ECO:0000269PubMed:19272188, ECO:0000269PubMed:9521325}. Note=The disease is caused by mutations affecting the gene represented in this entry.Sick sinus syndrome 1 (SSS1) [MIM:608567]: 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. SSS1 onset is in utero, infancy, or early childhood. {ECO:0000269PubMed:14523039, ECO:0000269PubMed:22795782}. Note=The disease is caused by mutations affecting the gene represented in this entry.Familial paroxysmal ventricular fibrillation 1 (VF1) [MIM:603829]: A cardiac arrhythmia marked by fibrillary contractions of the ventricular muscle due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the ventricle and by absence of atrial activity. {ECO:0000269PubMed:10940383}. Note=The disease is caused by mutations affecting the gene represented in this entry.Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. {ECO:0000269PubMed:18596570, ECO:0000269PubMed:19302788}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Atrial standstill 1 (ATRST1) [MIM:108770]: A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm. {ECO:0000269PubMed:12522116}. Note=The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry. A mutation in SCN5A has been detected in combination with a rare GJA5 genotype in a large family with atrial standstill.Cardiomyopathy, dilated 1E (CMD1E) [MIM:601154]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269PubMed:15466643}. Note=The disease is caused by mutations affecting the gene represented in this entry.Atrial fibrillation, familial, 10 (ATFB10) [MIM:614022]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269PubMed:18088563, ECO:0000269PubMed:18378609}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Found in jejunal circular smooth muscle cells (at protein level). Expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. Isoform 4 is expressed in brain. {ECO:0000269PubMed:12358675}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 28 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	28 [view]
Protein-Protein	28 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005216	ion channel activity
GO:0005248	voltage-gated sodium channel activity
GO:0005515	protein binding
GO:0005516	calmodulin binding
GO:0017134	fibroblast growth factor binding
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0030506	ankyrin binding
GO:0031625	ubiquitin protein ligase binding
GO:0044325	ion channel binding
GO:0050998	nitric-oxide synthase binding
GO:0086006	voltage-gated sodium channel activity involved in cardiac muscle cell action potential
GO:0097110	scaffold protein binding

Biological Process

GO:0002027	regulation of heart rate
GO:0003231	cardiac ventricle development
GO:0003360	brainstem development
GO:0006811	ion transport
GO:0006814	sodium ion transport
GO:0010765	positive regulation of sodium ion transport
GO:0014894	response to denervation involved in regulation of muscle adaptation
GO:0019228	neuronal action potential
GO:0021537	telencephalon development
GO:0021549	cerebellum development
GO:0035725	sodium ion transmembrane transport
GO:0042475	odontogenesis of dentin-containing tooth
GO:0045760	positive regulation of action potential
GO:0050679	positive regulation of epithelial cell proliferation
GO:0051899	membrane depolarization
GO:0055085	transmembrane transport
GO:0060048	cardiac muscle contraction
GO:0060307	regulation of ventricular cardiac muscle cell membrane repolarization
GO:0060371	regulation of atrial cardiac muscle cell membrane depolarization
GO:0060372	regulation of atrial cardiac muscle cell membrane repolarization
GO:0060373	regulation of ventricular cardiac muscle cell membrane depolarization
GO:0071277	cellular response to calcium ion
GO:0086002	cardiac muscle cell action potential involved in contraction
GO:0086004	regulation of cardiac muscle cell contraction
GO:0086005	ventricular cardiac muscle cell action potential
GO:0086010	membrane depolarization during action potential
GO:0086012	membrane depolarization during cardiac muscle cell action potential
GO:0086046	membrane depolarization involved in regulation of SA node cell action potential
GO:0086067	AV node cell to bundle of His cell communication
GO:0086069	bundle of His cell to Purkinje myocyte communication
GO:0086070	SA node cell to atrial cardiac muscle cell communication
GO:0086091	regulation of heart rate by cardiac conduction
GO:1902305	regulation of sodium ion transmembrane transport

Cellular Component

GO:0001518	voltage-gated sodium channel complex
GO:0005783	endoplasmic reticulum
GO:0005886	plasma membrane
GO:0005901	caveola
GO:0009986	cell surface
GO:0014704	intercalated disc
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016328	lateral plasma membrane
GO:0030315	T-tubule
GO:0042383	sarcolemma

Protein Structure and Domains

PDB ID

InterPro

IPR001696 Voltage gated sodium channel, alpha subunit
IPR005821 Ion transport domain
IPR008053 Voltage gated sodium channel, alpha-5 subunit
IPR010526 Sodium ion transport-associated
IPR013122 Polycystin cation channel, PKD1/PKD2
IPR024583 Domain of unknown function DUF3451

PFAM

PF00520
PF06512
PF08016
PF11933

PRINTS

PR00170
PR01666

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q14524