ID:SCN5A_HUMAN DESCRIPTION: RecName: Full=Sodium channel protein type 5 subunit alpha; AltName: Full=HH1; AltName: Full=Sodium channel protein cardiac muscle subunit alpha; AltName: Full=Sodium channel protein type V subunit alpha; AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.5; 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. SUBUNIT: Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 (By similarity). Interacts with NEDD4, NEDD4L, WWP2 and GPD1L. Interacts with CALM. Interacts with FGF13; the interaction is direct and may regulate SNC5A density at membranes and function. INTERACTION: P62158:CALM3; NbExp=2; IntAct=EBI-726858, EBI-397435; SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. 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. DOMAIN: The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position. PTM: Regulated through phosphorylation by CaMK2D (By similarity). PTM: Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2. DISEASE: Defects in SCN5A are a cause of progressive familial heart block type 1A (PFHB1A) [MIM:113900]; also known as Lenegre- Lev disease or progressive cardiac conduction defect (PCCD). PFHB1A is an autosomal dominant cardiac bundle branch disorder that may progress to complete heart block. PFHB1A is characterized by progressive alteration of cardiac conduction through the His- Purkinje system with right or left bundle branch block and widening of QRS complexes, leading to complete atrioventricular block and causing syncope and sudden death. DISEASE: Defects in SCN5A are the cause of long QT syndrome type 3 (LQT3) [MIM:603830]. Long QT syndromes are heart disorders 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. LQT3 inheritance is an autosomal dominant. DISEASE: Defects in SCN5A are the cause of Brugada syndrome type 1 (BRGDA1) [MIM:601144]. An autosomal dominant 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 (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset. DISEASE: Defects in SCN5A are the cause of sick sinus syndrome type 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, in which case it is considered to be a congenital disorder. DISEASE: Defects in SCN5A are the cause of familial paroxysmal ventricular fibrillation type 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. DISEASE: Defects in SCN5A may be a cause of 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. Long QT syndromes-associated mutations can be responsible for some of SIDS cases. DISEASE: Defects in SCN5A may be a cause of familial atrial standstill (FAS) [MIM:108770]. Atrial standstill is an extremely 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. DISEASE: Defects in SCN5A are the cause of cardiomyopathy dilated type 1E (CMD1E) [MIM:601154]; also known as dilated cardiomyopathy with conduction disorder and arrhythmia or dilated cardiomyopathy with conduction defect 2. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. DISEASE: Defects in SCN5A are the cause of familial atrial fibrillation type 10 (ATFB10) [MIM:614022]. ATFB10 is 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. MISCELLANEOUS: Na(+) channels in mammalian cardiac membrane have functional properties quite distinct from Na(+) channels in nerve and skeletal muscle. SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.5/SCN5A subfamily. SIMILARITY: Contains 1 IQ domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN5A";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00520 - Ion transport protein PF00612 - IQ calmodulin-binding motif PF06512 - Sodium ion transport-associated PF08016 - Polycystin cation channel PF11933 - Cytoplasmic domain of voltage-gated Na+ ion channel
ModBase Predicted Comparative 3D Structure on Q14524
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005216 ion channel activity GO:0005244 voltage-gated ion channel activity GO:0005248 voltage-gated sodium channel activity GO:0005272 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:0019904 protein domain specific 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:0086060 voltage-gated sodium channel activity involved in AV node cell action potential GO:0086061 voltage-gated sodium channel activity involved in bundle of His cell action potential GO:0086062 voltage-gated sodium channel activity involved in Purkinje myocyte action potential GO:0086063 voltage-gated sodium channel activity involved in SA node 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:0034765 regulation of ion transmembrane transport 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:0086014 atrial cardiac muscle cell action potential GO:0086015 SA node cell action potential GO:0086016 AV node cell action potential GO:0086043 bundle of His cell action potential GO:0086045 membrane depolarization during AV node cell action potential GO:0086046 membrane depolarization during SA node cell action potential GO:0086047 membrane depolarization during Purkinje myocyte cell action potential GO:0086048 membrane depolarization during bundle of His cell action potential GO:0086067 AV node cell to bundle of His cell communication GO:0086091 regulation of heart rate by cardiac conduction GO:0098912 membrane depolarization during atrial cardiac muscle cell action potential GO:1902305 regulation of sodium ion transmembrane transport
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
