Protein detail
SCN5A
Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1)
Entry name SCN5A | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count 24 | Protein classification |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
Sodium channel protein type 5 subunit alpha (Sodium channel protein cardiac muscle subunit alpha) (Sodium channel protein type V subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.5) (hH1)
Protein Function
- Predicted intracellular proteins
- Voltage-gated ion channels:Voltage-Gated Sodium Channels
- Transporters:Transporter channels and pores
- Disease related genes
- Human disease related genes:Cardiovascular diseases:Cardiac diseases
- FDA approved drug targets:Small molecule drugs
Transmembrane
130..149; Helical; Name=S1 of repeat I; 158..179; Helical; Name=S2 of repeat I; 189..209; Helical; Name=S3 of repeat I; 217..236; Helical; Name=S4 of repeat I; 250..272; Helical; Name=S5 of repeat I; 387..413; Helical; Name=S6 of repeat I; 720..737; Helical; Name=S1 of repeat II; 747..769; Helical; Name=S2 of repeat II; 776..796; Helical; Name=S3 of repeat II; 807..821; Helical; Name=S4 of repeat II; 839..860; Helical; Name=S5 of repeat II; 913..941; Helical; Name=S6 of repeat II; 1204..1225; Helical; Name=S1 of repeat III; 1237..1259; Helical; Name=S2 of repeat III; 1269..1291; Helical; Name=S3 of repeat III; 1298..1317; Helical; Name=S4 of repeat III; 1331..1355; Helical; Name=S5 of repeat III; 1446..1470; Helical; Name=S6 of repeat III; 1529..1547; Helical; Name=S1 of repeat IV; 1559..1580; Helical; Name=S2 of repeat IV; 1590..1612; Helical; Name=S3 of repeat IV; 1620..1640; Helical; Name=S4 of repeat IV; 1651..1679; Helical; Name=S5 of repeat IV; 1746..1771; Helical; Name=S6 of repeat IV
Transmembrane Count
24
Ensembl
Entrez Gene Symbol
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Tissue SpecifickidneyCell SpecificAlveolar cells type 1Blood Cell SpecificT-regBlood Lineage SpecificT-cellsSecretome LocationSecreted in other tissuesSecretome FunctionNo annotated function
Function & Pathway
Protein Function
- Predicted intracellular proteins
- Voltage-gated ion channels:Voltage-Gated Sodium Channels
- Transporters:Transporter channels and pores
- Disease related genes
- Human disease related genes:Cardiovascular diseases:Cardiac diseases
- FDA approved drug targets:Small molecule drugs
Cellular Component
- GO:0001518 voltage-gated sodium channel complex
- GO:0005654 nucleoplasm
- GO:0005730 nucleolus
- GO:0005783 endoplasmic reticulum
- GO:0005886 plasma membrane
- GO:0005901 caveola
- GO:0009986 cell surface
- GO:0014704 intercalated disc
- GO:0016020 membrane
- GO:0016328 lateral plasma membrane
- GO:0030018 Z disc
- GO:0030315 T-tubule
- GO:0042383 sarcolemma
- GO:0048471 perinuclear region of cytoplasm
Molecular Function
- 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:0019904 protein domain specific binding
- GO:0030506 ankyrin binding
- GO:0031625 ubiquitin protein ligase binding
- GO:0044325 transmembrane transporter 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
Reactome
Mediation Categories
Clinical-translation mediationFusion and delivery mediation
Relations & Evidence
Enzyme-Mediated Modification
46 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| SCN5A | CAMK2A | Q9UQM7 | S | 571 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 528 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 497 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 1,925 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 510 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 11 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 577 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 1,934 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 539 | phosphorylation | PhosphoSite | |
| SCN5A | CAMK2A | Q9UQM7 | S | 516 | phosphorylation | PhosphoSite |
Ligand-Receptor Signaling
34 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| transmembrane | transmembrane | UniProt_keyword | No | No | No | No | No |
| transmembrane | transmembrane | TopDB | No | No | No | No | No |
| transmembrane | transmembrane | LOCATE | No | No | No | No | No |
| transmembrane | transmembrane | Ramilowski_location | No | No | No | No | No |
| transmembrane | transmembrane | OmniPath | No | No | No | No | No |
| peripheral | peripheral | UniProt_topology | No | No | No | No | No |
| peripheral | peripheral | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | Cellinker | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
Regulatory Interaction Network
14 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| KCC2A | Q9UQM7 | SCN5A | Q14524 | Yes | Yes | No | PhosphoSite_norefSIGNORProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:28882890PhosphoSite:22101522SIGNOR:33410863PhosphoSite:25815641PhosphoSite:30385719PhosphoSite:33410863PhosphoSite:31622781PhosphoSite:19666841 |
| KCC2D | Q13557 | SCN5A | Q14524 | Yes | Yes | Yes | PhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperIntActSIGNOR_ProtMapperPhosphoSite_ProtMapper | SIGNOR:33410863IntAct:22514276SIGNOR:28882890SIGNOR:22514276ProtMapper:22514276 |
| FGF13 | Q92913 | SCN5A | Q14524 | Yes | No | Yes | Fantom5_LRdbCellTalkDBiTALKtalklrSIGNORconnectomeDB2020HINTCellinkerLRdbRamilowski2015 | talklr:21817159HINT:22705208connectomeDB2020:21817159Ramilowski2015:21817159LRdb:21817159Cellinker:21817159SIGNOR:20679355CellTalkDB:21817159HINT:33961781 |
| KCC2G | Q13555 | SCN5A | Q14524 | Yes | Yes | No | SIGNOR | SIGNOR:33410863 |
| KCC2B | Q13554 | SCN5A | Q14524 | Yes | Yes | No | SIGNOR | SIGNOR:33410863 |
| FGF12 | P61328 | SCN5A | Q14524 | Yes | No | Yes | DIPHINTSIGNOR | HINT:22705208DIP:22705208SIGNOR:20679355HINT:25232683HINT:33961781 |
| FYN | P06241 | SCN5A | Q14524 | Yes | No | Yes | phosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | PhosphoSite:15831816SIGNOR:15831816ProtMapper:15831816PhosphoSite:34373326 |
| SGK3 | Q96BR1 | SCN5A | Q14524 | Yes | Yes | No | SIGNOR | SIGNOR:33410863 |
| COMPLEX:O43741_P54619_P54646_Q13131_Q9UGI9_Q9UGJ0_Q9Y478 | SCN5A | Q14524 | Yes | Yes | No | SIGNOR | SIGNOR:33410863 | |
| NED4L | Q96PU5 | SCN5A | Q14524 | Yes | No | Yes | HPRDSIGNORBioGRID | BioGRID:28296171HPRD:15217910SIGNOR:23778145HPRD:15548568 |
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Protein Complex Composition
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential UltracentrifugationSize Exclusion Chromatography | Mass spectrometry | 1 | 30550287 |
Sequence, Structure & Domains
Sequences
Length
2,016
Mass
226,940
Sequence
MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEEAPRPQLDLQASKKLPDLYGNPPQELIGEPLEDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHPIRRAAVKILVHSLFNMLIMCTILTNCVFMAQHDPPPWTKYVEYTFTAIYTFESLVKILARGFCLHAFTFLRDPWNWLDFSVIIMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTIVGALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTALNGTNGSVEADGLVWESLDLYLSDPENYLLKNGTSDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFAWAFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLGSFYLVNLILAVVAMAYEEQNQATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVNSHERRSKRRKRMSSGTEECGEDRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTFRRRDLGSEADFADDENSTAGESESHHTSLLVPWPLRRTSAQGQPSPGTSAPGHALHGKKNSTVDCNGVVSLLGAGDPEATSPGSHLLRPVMLEHPPDTTTPSEEPGGPQMLTSQAPCVDGFEEPGARQRALSAVSVLTSALEELEESRHKCPPCWNRLAQRYLIWECCPLWMSIKQGVKLVVMDPFTDLTITMCIVLNTLFMALEHYNMTSEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQGWNIFDSIIVILSLMELGLSRMSNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKNYSELRDSDSGLLPRWHMMDFFHAFLIIFRILCGEWIETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDREMNNLQLALARIQRGLRFVKRTTWDFCCGLLRQRPQKPAALAAQGQLPSCIATPYSPPPPETEKVPPTRKETRFEEGEQPGQGTPGDPEPVCVPIAVAESDTDDQEEDEENSLGTEEESSKQQESQPVSGGPEAPPDSRTWSQVSATASSEAEASASQADWRQQWKAEPQAPGCGETPEDSCSEGSTADMTNTAELLEQIPDLGQDVKDPEDCFTEGCVRRCPCCAVDTTQAPGKVWWRLRKTCYHIVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKWVAYGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFEGMRVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFGRCINQTEGDLPLNYTIVNNKSQCESLNLTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQPQWEYNLYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKINILAKINLLFVAIFTGECIVKLAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKYFFSPTLFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMANFAYVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPTLPNSNGSRGDCGSPAVGILFFTTYIIISFLIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIWEKFDPEATQFIEYSVLSDFADALSEPLRIAKPNQISLINMDLPMVSGDRIHCMDILFAFTKRVLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSAMVIQRAFRRHLLQRSLKHASFLFRQQAGSGLSEEDAPEREGLIAYVMSENFSRPLGPPSSSSISSTSFPPSYDSVTRATSDNLQVRGSDYSHSEDLADFPPSPDRDRESIV
Alternative Products
Event=Alternative splicing; Named isoforms=6; Name=1; Synonyms=CAG-inclusive variant, Nav1.5c; IsoId=Q14524-1; Sequence=Displayed; Name=2; Synonyms=Nav1.5b; IsoId=Q14524-2; Sequence=VSP_037478; Name=3; IsoId=Q14524-3; Sequence=VSP_037477, VSP_037478, VSP_037481; Name=4; Synonyms=Nav1.5e, neonatal; IsoId=Q14524-4; Sequence=VSP_037477; Name=5; Synonyms=Ex18del, Nav1.5a; IsoId=Q14524-5; Sequence=VSP_037477, VSP_037479; Name=6; Synonyms=Ex24del, Nav1.5f; IsoId=Q14524-6; Sequence=VSP_037477, VSP_037480
Alternative Sequence
206..211; TTEFVD -> VSENIK (in isoform 3, isoform 4, isoform 5 and isoform 6); 1076; Missing (in isoform 2 and isoform 3); 1077..1130; Missing (in isoform 5); 1416..1433; Missing (in isoform 6); 1573..1604; Missing (in isoform 3)
3D Structural Models
Turn
273..276; 370..373; 717..720; 780..782; 836..838; 862..864; 1230..1232; 1366..1368; 1375..1377; 1440..1443; 1636..1639; 1679..1681; 1709..1713; 1823..1825; 1844..1846
Helix
121..128; 131..148; 157..178; 193..207; 218..223; 224..227; 228..231; 236..250; 253..272; 304..307; 349..351; 358..369; 374..385; 387..389; 390..399; 401..428; 700..714; 721..734; 745..770; 773..776; 783..797; 806..812; 813..819; 825..835; 842..861; 865..868; 884..896; 900..910; 912..942; 1191..1203; 1205..1220; 1221..1224; 1233..1267; 1272..1290; 1299..1303; 1304..1315; 1318..1329; 1332..1356; 1381..1386; 1405..1416; 1422..1429; 1444..1446; 1447..1477; 1491..1500; 1516..1526; 1528..1546; 1554..1581; 1592..1608; 1609..1614; 1621..1626; 1627..1635; 1641..1651; 1654..1678; 1697..1708; 1714..1720; 1745..1780; 1788..1801; 1811..1813; 1814..1820; 1832..1837; 1850..1862; 1866..1882; 1886..1888; 1896..1926
Beta Strand
185..191; 232..235; 279..282; 288..292; 294..302; 318..320; 328..332; 339..342; 355..357; 738..740; 872..874; 1269..1271; 1361..1364; 1394..1397; 1402..1404; 1433..1436; 1480..1482; 1501..1504; 1583..1586; 1589..1591; 1690..1696; 1724..1727; 1735..1737; 1807..1810; 1841..1843; 1847..1849; 1891..1894
3D Structure
Electron microscopy (5); NMR spectroscopy (3); X-ray crystallography (6)
Domain & Motif Annotations
Compositional Bias
41..52; Basic and acidic residues; 491..503; Basic and acidic residues; 509..528; Polar residues; 570..580; Polar residues; 1015..1030; Basic and acidic residues; 1033..1044; Low complexity; 1054..1071; Acidic residues; 1096..1113; Low complexity; 1959..1979; Low complexity; 1981..1990; Polar residues
Repeat
113..420; I; 699..969; II; 1187..1501; III; 1510..1807; IV
Domain (CC)
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.; DOMAIN: The IQ domain mediates association with calmodulin.
Domain (FT)
1901..1930; IQ
Region
28..56; Disordered; 461..591; Disordered; 1005..1141; Disordered; 1839..1901; Interaction with FGF13; 1959..2016; Disordered; 1974..1977; Interaction with NEDD4, NEDD4L and WWP2
Protein Families
- Sodium channel (TC 1.A.1.10) family
- Nav1.5/SCN5A subfamily
Sequence Similarities
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.5/SCN5A subfamily.
Clinical Relevance
Related Diseases
Biomarker
Withdrawn from market; Phase 1; Approved; Discontinued in Preregistration; Discontinued in Phase 3
Drugs
PROPAFENONECHLOROPROCAINEOXCARBAZEPINEPRILOCAINE HYDROCHLORIDEPRILOCAINELITHIUMETHOTOINETIDOCAINE HYDROCHLORIDEINDECAINIDE HYDROCHLORIDETOCAINIDE HYDROCHLORIDEFOSPHENYTOINPROCAINE HYDROCHLORIDEFLECAINIDE ACETATEMEPIVACAINE HYDROCHLORIDEMEPHENYTOINAZD1305LIDOCAINELICARBAZEPINEESLICARBAZEPINE ACETATEDISOPYRAMIDE PHOSPHATECENOBAMATEDRONEDARONE HYDROCHLORIDEDYCLONINEQUINIDINE SULFATEHEXYLCAINESAFINAMIDEZONISAMIDEEVENAMIDENERISPIRDINERALFINAMIDEPROPARACAINE HYDROCHLORIDERUFINAMIDEBENZONATATERANOLAZINEQUINIDINETETRACAINEPROPOXYCAINE HYDROCHLORIDEPROPAFENONE HYDROCHLORIDEAZD7009DISOPYRAMIDEDYCLONINE HYDROCHLORIDEESLICARBAZEPINEMORICIZINEPRIMIDONEIRAMPANELENCAINIDEPHENYTOIN SODIUMNULLDICHLOROBENZYL ALCOHOLRILUZOLECOCAINE HYDROCHLORIDEMEXILETINETETRODOTOXINTOPIRAMATEHEXYLCAINE HYDROCHLORIDEPHENAZOPYRIDINE HYDROCHLORIDECOCAINEQUINIDINE GLUCONATEORPHENADRINE HYDROCHLORIDECISAPRIDEPROCAINAMIDE HYDROCHLORIDELIDOCAINE HYDROCHLORIDEBEPRIDILINDECAINIDEMERETHOXYLLINE PROCAINEDIBUCAINEORPHENADRINE CITRATEPILSICAINIDEQUINIDINE POLYGALACTURONATEROPIVACAINE HYDROCHLORIDEARTICAINE HYDROCHLORIDEPROCAINAMIDETOCAINIDELOMERIZINECLOMIPRAMINECARBAMAZEPINEENCAINIDE HYDROCHLORIDEDIBUCAINE HYDROCHLORIDENKTR-171MEXILETINE HYDROCHLORIDEPHENACEMIDEAPRINDINELACOSAMIDEMORICIZINE HYDROCHLORIDEVERNAKALANT HYDROCHLORIDEAMIODARONE HYDROCHLORIDELAMOTRIGINEBENOXINATE HYDROCHLORIDEPRENYLAMINE