Sodium channel protein type 5 subunit alpha
Also known as: SCN5A
Function
Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues. Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat. Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity).
Classification
- Family (Pfam)
- PF00520 Ion_trans, PF24609 IQ_SCN5A_C, PF06512 Na_trans_assoc, PF11933 Na_trans_cytopl
- InterPro
- Ion_trans_dom, IQ_SCN5A_C, Na_channel_a5su, Na_channel_asu, Na_chnl_inactivation_gate, Na_trans_assoc_dom, Na_trans_cytopl, VGCC_Ca_Na, Volt_channel_dom_sf
- Functional cluster
- Membrane Transporters & GPCRs
Experimental structures · PDB · 14
- 2KBI NMR
- 2L53 NMR
- 4DCK X-ray 2.20A
- 4DJC X-ray 1.35A
- 4JQ0 X-ray 3.84A
- 4OVN X-ray 2.80A
- 5DBR X-ray 2.25A
- 6LQA EM 3.30A
- 6MUD X-ray 2.69A
- 7DTC EM 3.30A
- 7L83 NMR
- 8VYJ EM 3.60A
- … and 2 more
A predicted model is available from AlphaFold.
Gene Ontology · 65
- GO:0005901 caveola
- GO:0009986 cell surface
- GO:0005783 endoplasmic reticulum
- GO:0014704 intercalated disc
- GO:0016328 lateral plasma membrane
- GO:0016020 membrane
- GO:0048471 perinuclear region of cytoplasm
- GO:0005886 plasma membrane
- GO:0042383 sarcolemma
- GO:0030315 T-tubule
- GO:0001518 voltage-gated sodium channel complex
- GO:0030018 Z disc
- GO:0030506 ankyrin binding
- GO:0005516 calmodulin binding
- GO:0019899 enzyme binding
- GO:0017134 fibroblast growth factor binding
- GO:0050998 nitric-oxide synthase binding
- GO:0019904 protein domain specific binding
- GO:0019901 protein kinase binding
- GO:0097110 scaffold protein binding
- GO:0044325 transmembrane transporter binding
- GO:0031625 ubiquitin protein ligase binding
- GO:0005248 voltage-gated sodium channel activity
- 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:0086006 voltage-gated sodium channel activity involved in cardiac muscle 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:0086014 atrial cardiac muscle cell action potential
- GO:0086016 AV node cell action potential
- GO:0086067 AV node cell to bundle of His cell communication
- GO:0003360 brainstem development
- GO:0086043 bundle of His cell action potential
- GO:0003161 cardiac conduction system development
- GO:0086002 cardiac muscle cell action potential involved in contraction
- GO:0060048 cardiac muscle contraction
- GO:0003231 cardiac ventricle development
- GO:0071277 cellular response to calcium ion
- GO:0021549 cerebellum development
- GO:0051899 membrane depolarization
- GO:0086010 membrane depolarization during action potential
- GO:0098912 membrane depolarization during atrial cardiac muscle cell action potential
- GO:0086045 membrane depolarization during AV node cell action potential
- GO:0086048 membrane depolarization during bundle of His cell action potential
- GO:0086012 membrane depolarization during cardiac muscle cell action potential
- GO:0086047 membrane depolarization during Purkinje myocyte cell action potential
- GO:0086046 membrane depolarization during SA node cell action potential
- GO:0042475 odontogenesis of dentin-containing tooth
- GO:0045760 positive regulation of action potential
- GO:0050679 positive regulation of epithelial cell proliferation
- GO:0010765 positive regulation of sodium ion transport
- GO:0060371 regulation of atrial cardiac muscle cell membrane depolarization
- GO:0060372 regulation of atrial cardiac muscle cell membrane repolarization
- GO:0086004 regulation of cardiac muscle cell contraction
- GO:0002027 regulation of heart rate
- GO:0086091 regulation of heart rate by cardiac conduction
- GO:1902305 regulation of sodium ion transmembrane transport
- GO:0060373 regulation of ventricular cardiac muscle cell membrane depolarization
- GO:0060307 regulation of ventricular cardiac muscle cell membrane repolarization
- GO:0014894 response to denervation involved in regulation of muscle adaptation
- GO:0086015 SA node cell action potential
- GO:0035725 sodium ion transmembrane transport
- GO:0006814 sodium ion transport
- GO:0021537 telencephalon development
- GO:0086005 ventricular cardiac muscle cell action potential
Disease associations
- atrial standstill 1 MONDO:0007171
- progressive familial heart block, type 1A MONDO:0007240
- obsolete sudden infant death syndrome MONDO:0010086
- Brugada syndrome 1 MONDO:0011001
- dilated cardiomyopathy 1E MONDO:0011003
- ventricular fibrillation, paroxysmal familial, type 1 MONDO:0011376
- long QT syndrome 3 MONDO:0011377
- sick sinus syndrome 1 MONDO:0024562
- atrial fibrillation, familial, 10 MONDO:0013530
Drugs targeting this protein · 62
- OXCARBAZEPINE blocker
- CARBAMAZEPINE blocker
- ETHOTOIN blocker
- PRILOCAINE blocker
- MORICIZINE HYDROCHLORIDE blocker
- INDECAINIDE HYDROCHLORIDE blocker
- ORPHENADRINE CITRATE blocker
- LIDOCAINE HYDROCHLORIDE blocker
- QUINIDINE GLUCONATE blocker
- MEPIVACAINE HYDROCHLORIDE blocker
- PROPARACAINE HYDROCHLORIDE blocker
- DYCLONINE HYDROCHLORIDE blocker
- PRILOCAINE HYDROCHLORIDE blocker
- ETIDOCAINE HYDROCHLORIDE blocker
- MEXILETINE HYDROCHLORIDE blocker
- DIBUCAINE HYDROCHLORIDE blocker
- BENOXINATE HYDROCHLORIDE blocker
- HEXYLCAINE HYDROCHLORIDE blocker
- TOCAINIDE HYDROCHLORIDE blocker
- ARTICAINE HYDROCHLORIDE blocker
- FLECAINIDE ACETATE blocker
- PROCAINE HYDROCHLORIDE blocker
- DISOPYRAMIDE PHOSPHATE blocker
- PHENAZOPYRIDINE HYDROCHLORIDE blocker
- ORPHENADRINE HYDROCHLORIDE blocker
- PROPAFENONE HYDROCHLORIDE blocker
- DRONEDARONE HYDROCHLORIDE blocker
- RUFINAMIDE blocker
- TETRACAINE HYDROCHLORIDE blocker
- RANOLAZINE blocker
- PHENYTOIN blocker
- PHENYTOIN SODIUM blocker
- PROPOXYCAINE HYDROCHLORIDE blocker
- ROPIVACAINE HYDROCHLORIDE blocker
- ENCAINIDE HYDROCHLORIDE blocker
- VERNAKALANT HYDROCHLORIDE blocker
- NERISPIRDINE blocker
- RALFINAMIDE blocker
- TOPIRAMATE blocker
- PRENYLAMINE blocker
- IRAMPANEL blocker
- ESLICARBAZEPINE blocker
- DICHLOROBENZYL ALCOHOL blocker
- AZD7009 blocker
- AZD1305 blocker
- EVENAMIDE blocker
- QUINIDINE SULFATE blocker
- CENOBAMATE inhibitor
- COCAINE HYDROCHLORIDE blocker
- LACOSAMIDE blocker
- PROCAINAMIDE HYDROCHLORIDE blocker
- TETRACAINE blocker
- LAMOTRIGINE blocker
- RILUZOLE blocker
- ZONISAMIDE blocker
- LIDOCAINE blocker
- PRIMIDONE blocker
- MEPHENYTOIN blocker
- ESLICARBAZEPINE ACETATE blocker
- PHENACEMIDE blocker
- FOSPHENYTOIN SODIUM blocker
- CHLOROPROCAINE HYDROCHLORIDE blocker
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Sodium channel protein type 5 subunit alpha 0.98
- Sodium channel protein type 5 subunit alpha 0.97
- Sodium channel protein type 10 subunit alpha 0.95
- Sodium channel protein type 10 subunit alpha 0.95
- Sodium channel protein type 10 subunit alpha 0.94
- Sodium channel protein type 10 subunit alpha 0.93
- Sodium channel protein type 10 subunit alpha 0.93
- Sodium channel protein type 11 subunit alpha 0.90
- Sodium channel protein type 11 subunit alpha 0.90
- Sodium channel protein type 11 subunit alpha 0.90
- Sodium channel protein type 4 subunit alpha 0.89
- Sodium channel protein type 4 subunit alpha 0.89
Co-cited proteins · studied together in the literature
- Glycerol-3-phosphate dehydrogenase 1-like protein 1 shared papers
- Ran guanine nucleotide release factor 2 shared papers
- Voltage-gated inwardly rectifying potassium channel KCNH2 6 shared papers
- Sodium channel protein type 5 subunit alpha 2 shared papers
- Sodium channel regulatory subunit beta-1 2 shared papers
- Delta-actitoxin-Axm1b 1 shared papers
- Potassium voltage-gated channel subfamily KQT member 1 5 shared papers
- Potassium voltage-gated channel subfamily E member 1 3 shared papers
- Sodium channel protein type 5 subunit alpha 2 shared papers
- E3 ubiquitin-protein ligase NEDD4-like 2 shared papers
- Potassium voltage-gated channel subfamily E member 2 2 shared papers
- Sodium channel protein type 1 subunit alpha 2 shared papers
Literature · 111 cited papers
- Critical role of extracellular loops in differential modulations of TTX-sensitive and TTX-resistant Na<sub>v</sub> channels. Proc. Natl. Acad. Sci. U.S.A. · 2025
- Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nat. Commun. · 2023
- Analysis of incidental findings in Qatar genome participants reveals novel functional variants in LMNA and DSP. Hum. Mol. Genet. · 2022
- Structure of human Nav1.5 reveals the fast inactivation-related segments as a mutational hotspot for the long QT syndrome. Proc. Natl. Acad. Sci. U.S.A. · 2021
- Compound heterozygous SCN5A mutations in severe sodium channelopathy with Brugada syndrome: a case report. Front. Cardiovasc. Med. · 2020
- SCN5A(K817E), a novel Brugada syndrome-associated mutation that alters the activation gating of NaV1.5 channel. Heart Rhythm · 2016
- Molecular determinant for the tarantula toxin Jingzhaotoxin-I slowing the fast inactivation of voltage-gated sodium channels. Toxicon · 2016
- SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia. Proc. Natl. Acad. Sci. U.S.A. · 2015
- De novo mutation in the SCN5A gene associated with brugada syndrome. Cell. Physiol. Biochem. · 2015
- Regulation of the NaV1.5 cytoplasmic domain by calmodulin. Nat. Commun. · 2014
- Gating-pore currents demonstrate selective and specific modulation of individual sodium channel voltage-sensors by biological toxins. Mol. Pharmacol. · 2014
- Electrophysiological characteristics of a SCN5A voltage sensors mutation R1629Q associated with Brugada syndrome. PLoS ONE · 2013
- … and 99 more in the literature graph