ID  Q14524;
PN  Sodium channel protein type 5 subunit alpha;
GN  SCN5A;
OS  9606;
SL  Nucleus Position: SL-0198;
SL  Comments: Cell membrane {ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430}; Multi-pass membrane protein {ECO:0000250|UniProtKB:D0E0C2}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:21447824}. Cell membrane, sarcolemma, T- tubule {ECO:0000250|UniProtKB:P15389}. Note=RANGRF promotes trafficking to the cell membrane. {ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23420830}.
DR  UNIPROT: Q14524;
DR  UNIPROT: A5H1P8;
DR  UNIPROT: A6N922;
DR  UNIPROT: A6N923;
DR  UNIPROT: B2RTU0;
DR  UNIPROT: E7ET19;
DR  UNIPROT: E9PEF3;
DR  UNIPROT: E9PEK2;
DR  UNIPROT: E9PFW7;
DR  UNIPROT: Q59H93;
DR  UNIPROT: Q75RX9;
DR  UNIPROT: Q75RY0;
DR  UNIPROT: Q86UR3;
DR  UNIPROT: Q8IZC9;
DR  UNIPROT: Q96J69;
DR  PDB: 2KBI;
DR  PDB: 2L53;
DR  PDB: 4DCK;
DR  PDB: 4DJC;
DR  PDB: 4JQ0;
DR  PDB: 4OVN;
DR  PDB: 5DBR;
DR  PDB: 6LQA;
DR  PDB: 6MUD;
DR  PDB: 7DTC;
DR  PDB: 7L83;
DR  Pfam: PF00520;
DR  Pfam: PF06512;
DR  Pfam: PF11933;
DR  OMIM: 108770;
DR  OMIM: 113900;
DR  OMIM: 272120;
DR  OMIM: 600163;
DR  OMIM: 601144;
DR  OMIM: 601154;
DR  OMIM: 603829;
DR  OMIM: 603830;
DR  OMIM: 608567;
DR  OMIM: 614022;
DR  DisGeNET: 6331;
DE  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 (PubMed:1309946, PubMed:21447824, PubMed:25370050, PubMed:23420830, PubMed:23085483, PubMed:26279430, PubMed:26392562, PubMed:26776555). It is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946). This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (PubMed:19074138). {ECO:0000269|PubMed:1309946, ECO:0000269|PubMed:19074138, ECO:0000269|PubMed:21447824, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:25370050, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:26776555}.
DE  Disease: 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:0000269|PubMed:11234013, ECO:0000269|PubMed:11804990, ECO:0000269|PubMed:12569159, ECO:0000269|PubMed:12574143, ECO:0000269|PubMed:19251209, ECO:0000269|PubMed:23420830}. Note=The disease is caused by variants 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:0000269|PubMed:10377081, ECO:0000269|PubMed:10508990, ECO:0000269|PubMed:10590249, ECO:0000269|PubMed:10627139, ECO:0000269|PubMed:10911008, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11304498, ECO:0000269|PubMed:11410597, ECO:0000269|PubMed:11710892, ECO:0000269|PubMed:11889015, ECO:0000269|PubMed:11997281, ECO:0000269|PubMed:12209021, ECO:0000269|PubMed:12454206, ECO:0000269|PubMed:12673799, ECO:0000269|PubMed:15840476, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:16922724, ECO:0000269|PubMed:18060054, ECO:0000269|PubMed:18451998, ECO:0000269|PubMed:18708744, ECO:0000269|PubMed:18848812, ECO:0000269|PubMed:18929331, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:26392562, ECO:0000269|PubMed:7651517, ECO:0000269|PubMed:7889574, ECO:0000269|PubMed:8541846, ECO:0000269|PubMed:9506831, ECO:0000269|PubMed:9686753, ECO:0000269|Ref.35}. Note=The disease is caused by variants 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:0000269|PubMed:10532948, ECO:0000269|PubMed:10618304, ECO:0000269|PubMed:10690282, ECO:0000269|PubMed:11410597, ECO:0000269|PubMed:11748104, ECO:0000269|PubMed:11823453, 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:20129283, ECO:0000269|PubMed:23085483, ECO:0000269|PubMed:23420830, ECO:0000269|PubMed:24167619, ECO:0000269|PubMed:26279430, ECO:0000269|PubMed:26776555, ECO:0000269|PubMed:32850980, ECO:0000269|PubMed:9521325}. Note=The disease is caused by variants 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:0000269|PubMed:11748104, ECO:0000269|PubMed:14523039, ECO:0000269|PubMed:22795782}. Note=The disease is caused by variants 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:0000269|PubMed:10940383}. Note=The disease is caused by variants 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:0000269|PubMed:18596570, ECO:0000269|PubMed:19302788}. Note=Disease susceptibility is associated with variants 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:0000269|PubMed:12522116, ECO:0000269|PubMed:23420830}. Note=The disease may be caused by variants 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:0000269|PubMed:15466643, ECO:0000269|PubMed:23420830}. Note=The disease is caused by variants 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:0000269|PubMed:18088563, ECO:0000269|PubMed:18378609}. Note=The disease is caused by variants affecting the gene represented in this entry.
DE  Reference Proteome: Yes;
DE  Interaction: Q9NY99; IntAct: EBI-8556892; Score: 0.51
DE  Interaction: Q61234; IntAct: EBI-8669491; Score: 0.40
DE  Interaction: P41220; IntAct: EBI-737552; Score: 0.00
DE  Interaction: P02768; IntAct: EBI-1222961; Score: 0.35
DE  Interaction: P62158; IntAct: EBI-2930225; Score: 0.93
DE  Interaction: P26045; IntAct: EBI-8620386; Score: 0.53
DE  Interaction: Q99873; IntAct: EBI-8673374; Score: 0.47
DE  Interaction: O60678; IntAct: EBI-8673437; Score: 0.47
DE  Interaction: O14744; IntAct: EBI-8673420; Score: 0.27
DE  Interaction: Q13557; IntAct: EBI-9637464; Score: 0.61
DE  Interaction: P11275; IntAct: EBI-9674620; Score: 0.44
DE  Interaction: Q12959; IntAct: EBI-11793004; Score: 0.40
DE  Interaction: Q9Y3B6; IntAct: EBI-24496050; Score: 0.56
DE  Interaction: Q8N9N5; IntAct: EBI-24609814; Score: 0.56
DE  Interaction: Q8WW24; IntAct: EBI-24627863; Score: 0.56
DE  Interaction: Q96E35; IntAct: EBI-24558772; Score: 0.60
DE  Interaction: Q49AR9; IntAct: EBI-24601634; Score: 0.56
DE  Interaction: Q8N335; IntAct: EBI-13644311; Score: 0.40
DE  Interaction: Q13424; IntAct: EBI-15712197; Score: 0.35
DE  Interaction: P29476; IntAct: EBI-15712197; Score: 0.35
DE  Interaction: Q6Q477; IntAct: EBI-15712197; Score: 0.35
DE  Interaction: Q12955; IntAct: EBI-15807622; Score: 0.44
DE  Interaction: Q92913; IntAct: EBI-15987728; Score: 0.35
DE  Interaction: P61328; IntAct: EBI-15987771; Score: 0.54
DE  Interaction: P0DOF2; IntAct: EBI-25603126; Score: 0.35
DE  Interaction: P46934; IntAct: EBI-30832580; Score: 0.44
GO  GO:0005901;
GO  GO:0009986;
GO  GO:0005783;
GO  GO:0016021;
GO  GO:0014704;
GO  GO:0016328;
GO  GO:0005730;
GO  GO:0005654;
GO  GO:0048471;
GO  GO:0005886;
GO  GO:0042383;
GO  GO:0030315;
GO  GO:0001518;
GO  GO:0030018;
GO  GO:0030506;
GO  GO:0005516;
GO  GO:0019899;
GO  GO:0017134;
GO  GO:0050998;
GO  GO:0019904;
GO  GO:0019901;
GO  GO:0097110;
GO  GO:0044325;
GO  GO:0031625;
GO  GO:0005244;
GO  GO:0005248;
GO  GO:0086060;
GO  GO:0086061;
GO  GO:0086006;
GO  GO:0086062;
GO  GO:0086063;
GO  GO:0086014;
GO  GO:0086016;
GO  GO:0086067;
GO  GO:0003360;
GO  GO:0086043;
GO  GO:0003161;
GO  GO:0086002;
GO  GO:0060048;
GO  GO:0003231;
GO  GO:0071277;
GO  GO:0021549;
GO  GO:0051899;
GO  GO:0086010;
GO  GO:0098912;
GO  GO:0086045;
GO  GO:0086048;
GO  GO:0086012;
GO  GO:0086047;
GO  GO:0086046;
GO  GO:0019228;
GO  GO:0042475;
GO  GO:0045760;
GO  GO:0050679;
GO  GO:0010765;
GO  GO:0060371;
GO  GO:0060372;
GO  GO:0086004;
GO  GO:0002027;
GO  GO:0086091;
GO  GO:1902305;
GO  GO:0060373;
GO  GO:0060307;
GO  GO:0014894;
GO  GO:0086015;
GO  GO:0035725;
GO  GO:0006814;
GO  GO:0021537;
GO  GO:0086005;
TP  Membrane Topology: Transmembrane; Source: UniProt - By Similarity {ECO:0000250|UniProtKB:D0E0C2};
SQ  MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEEAPRPQLDLQASKKLPDLYGNPPQELIGEPL
SQ  EDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHPIRRAAVKILVHSLFNMLIMCTILTNCVFMAQHDPPPWTKYV
SQ  EYTFTAIYTFESLVKILARGFCLHAFTFLRDPWNWLDFSVIIMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTIV
SQ  GALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTALNGTNGSVEADGLVWESLDLYLSDPENYLLKNGT
SQ  SDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFAWAFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLG
SQ  SFYLVNLILAVVAMAYEEQNQATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVNSHERRSKRRK
SQ  RMSSGTEECGEDRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTFRRRDLGSEADFADDENSTAGESESHHTS
SQ  LLVPWPLRRTSAQGQPSPGTSAPGHALHGKKNSTVDCNGVVSLLGAGDPEATSPGSHLLRPVMLEHPPDTTTPSEEPGGP
SQ  QMLTSQAPCVDGFEEPGARQRALSAVSVLTSALEELEESRHKCPPCWNRLAQRYLIWECCPLWMSIKQGVKLVVMDPFTD
SQ  LTITMCIVLNTLFMALEHYNMTSEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQGWNIFDSIIVILSLMELGLSR
SQ  MSNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKNYSELRDSDSGLLPRWH
SQ  MMDFFHAFLIIFRILCGEWIETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDREMNNLQ
SQ  LALARIQRGLRFVKRTTWDFCCGLLRQRPQKPAALAAQGQLPSCIATPYSPPPPETEKVPPTRKETRFEEGEQPGQGTPG
SQ  DPEPVCVPIAVAESDTDDQEEDEENSLGTEEESSKQQESQPVSGGPEAPPDSRTWSQVSATASSEAEASASQADWRQQWK
SQ  AEPQAPGCGETPEDSCSEGSTADMTNTAELLEQIPDLGQDVKDPEDCFTEGCVRRCPCCAVDTTQAPGKVWWRLRKTCYH
SQ  IVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKWVAYGFKKYFTNAWCWLDFLIVD
SQ  VSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFEGMRVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKF
SQ  GRCINQTEGDLPLNYTIVNNKSQCESLNLTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQPQW
SQ  EYNLYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPLNKYQGF
SQ  IFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKINILAKINLLFVAIFTGECIVKLAALRHYYFTNSWNIFDFVVVI
SQ  LSIVGTVLSDIIQKYFFSPTLFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMANFA
SQ  YVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPTLPNSNGSRGDCGSPAVGILFFTTYIIISF
SQ  LIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIWEKFDPEATQFIEYSVLSDFADALSEPLRIAKPNQISLINMDL
SQ  PMVSGDRIHCMDILFAFTKRVLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSAMVIQRAFRRHLLQRS
SQ  LKHASFLFRQQAGSGLSEEDAPEREGLIAYVMSENFSRPLGPPSSSSISSTSFPPSYDSVTRATSDNLQVRGSDYSHSED
SQ  LADFPPSPDRDRESIV
//