MGP Database

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MGP002761

UniProt Annotations

Entry Information
Gene Namesodium channel, voltage gated, type V alpha subunit
Protein EntrySCN5A_HUMAN
UniProt IDQ14524
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=6; Name=1; Synonyms=CAG-inclusive variant, Nav1.5c; IsoId=Q14524-1; Sequence=Displayed; Note=Most abundant isoform in heart.; Name=2; Synonyms=Nav1.5b; IsoId=Q14524-2; Sequence=VSP_037478; Note=Very abundant isoform.; Name=3; IsoId=Q14524-3; Sequence=VSP_037477, VSP_037478, VSP_037481; Name=4; Synonyms=Nav1.5e, neonatal; IsoId=Q14524-4; Sequence=VSP_037477; Note=Abundantly expressed in neonatal brain and heart, slower kinetics of activation and inactivation.; Name=5; Synonyms=Ex18del, Nav1.5a; IsoId=Q14524-5; Sequence=VSP_037477, VSP_037479; Note=Only detected in neuroblastoma in humans.; Name=6; Synonyms=Ex24del, Nav1.5f; IsoId=Q14524-6; Sequence=VSP_037477, VSP_037480; Note=High expression in brain where it accounts for nearly 50% of the total transcripts. Non-functional channel, may exist to limit the number of undesired functional Nav1.5 channels.;
DiseaseAtrial 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:0000269|PubMed:18088563, ECO:0000269|PubMed:18378609}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseAtrial 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:0000269|PubMed: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.
DiseaseBrugada 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:0000269|PubMed:11748104, ECO:0000269|PubMed:11901046, ECO:0000269|PubMed:12051963, ECO:0000269|PubMed:12106943, ECO:0000269|PubMed:15023552, ECO:0000269|PubMed:15338453, ECO:0000269|PubMed:15579534, ECO:0000269|PubMed:15851320, ECO:0000269|PubMed:16266370, ECO:0000269|PubMed:16325048, ECO:0000269|PubMed:16616735, ECO:0000269|PubMed:17075016, ECO:0000269|PubMed:17081365, ECO:0000269|PubMed:17198989, ECO:0000269|PubMed:18252757, ECO:0000269|PubMed:18341814, ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:18456723, ECO:0000269|PubMed:18616619, ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:19272188, ECO:0000269|PubMed:9521325}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseCardiomyopathy, 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:0000269|PubMed:15466643}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseFamilial 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:0000269|PubMed:10940383}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseLong 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:0000269|PubMed:10377081, ECO:0000269|PubMed:10508990, ECO:0000269|PubMed:10627139, ECO:0000269|PubMed:10911008, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11304498, ECO:0000269|PubMed:11997281, ECO:0000269|PubMed:12209021, ECO:0000269|PubMed:12673799, ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:18060054, ECO:0000269|PubMed:18708744, ECO:0000269|PubMed:18848812, ECO:0000269|PubMed:18929331, ECO:0000269|PubMed:7651517, ECO:0000269|PubMed:7889574, ECO:0000269|PubMed:8541846, ECO:0000269|PubMed:9506831, ECO:0000269|PubMed:9686753, ECO:0000269|Ref.30}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseProgressive 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:0000269|PubMed:12569159, ECO:0000269|PubMed:12574143, ECO:0000269|PubMed:19251209}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseSick 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:0000269|PubMed:14523039, ECO:0000269|PubMed:22795782}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseSudden 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:0000269|PubMed:18596570, ECO:0000269|PubMed:19302788}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
DomainThe IQ domain mediates association with calmodulin.
DomainThe 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.
FunctionThis 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:0000269|PubMed:19074138}.
InteractionP62158:CALM3; NbExp=2; IntAct=EBI-726858, EBI-397435; Q13557:CAMK2D; NbExp=16; IntAct=EBI-726858, EBI-351018; Q99873:PRMT1; NbExp=2; IntAct=EBI-726858, EBI-78738; O60678:PRMT3; NbExp=2; IntAct=EBI-726858, EBI-2809009; P26045:PTPN3; NbExp=2; IntAct=EBI-726858, EBI-1047946;
MiscellaneousNa(+) channels in mammalian cardiac membrane have functional properties quite distinct from Na(+) channels in nerve and skeletal muscle.
PtmPhosphorylation at Ser-1503 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents. {ECO:0000250}.
PtmRegulated through phosphorylation by CaMK2D. {ECO:0000250}.
PtmUbiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2. {ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15548568}.
SimilarityBelongs to the sodium channel (TC 1.A.1.10) family. Nav1.5/SCN5A subfamily. {ECO:0000305}.
SimilarityContains 1 IQ domain. {ECO:0000305}.
Subcellular LocationMembrane {ECO:0000269|PubMed:19074138}; Multi-pass membrane protein {ECO:0000269|PubMed:19074138}.
SubunitInteracts 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. {ECO:0000250, ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15548568, ECO:0000269|PubMed:19666841, ECO:0000269|PubMed:21167176, ECO:0000269|PubMed:21817159, ECO:0000269|PubMed:22705208}.
Tissue SpecificityFound 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:0000269|PubMed:12358675}.
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