Sodium channel protein type 3 subunit alpha
Also known as: KIAA1356, NAC3, SCN3A
Function
Pore-forming subunit of Nav1.3, 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. In some secretory cell types, it also participates in cell excitability through membrane depolarization and regulates cells responsiveness to stimuli triggering secretion. For instance, it controls the release of serotonin/5-hydroxytryptamine by enterochromaffin cells and is required for both glucagon- and glucose-induced insulin secretion in pancreatic endocrine cells (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_asu, Na_chnl_inactivation_gate, Na_trans_assoc_dom, Na_trans_cytopl, VGCC_Ca_Na, Volt_channel_dom_sf
- Functional cluster
- DEAD-Box RNA Helicases & Biogenesis Factors
Experimental structures · PDB · 2
A predicted model is available from AlphaFold.
Gene Ontology · 10
- GO:0009925 basal plasma membrane
- GO:0005737 cytoplasm
- GO:0005886 plasma membrane
- GO:0001518 voltage-gated sodium channel complex
- GO:0005248 voltage-gated sodium channel activity
- GO:0048266 behavioral response to pain
- GO:0086002 cardiac muscle cell action potential involved in contraction
- GO:0086010 membrane depolarization during action potential
- GO:0035725 sodium ion transmembrane transport
- GO:0006814 sodium ion transport
Disease associations
- epilepsy, familial focal, with variable foci 4 MONDO:0054776
- developmental and epileptic encephalopathy, 62 MONDO:0033371
Drugs targeting this protein · 56
- 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
- BENOXINATE HYDROCHLORIDE blocker
- HEXYLCAINE HYDROCHLORIDE blocker
- TOCAINIDE HYDROCHLORIDE blocker
- ARTICAINE HYDROCHLORIDE blocker
- PROCAINE HYDROCHLORIDE blocker
- DISOPYRAMIDE PHOSPHATE blocker
- PHENAZOPYRIDINE HYDROCHLORIDE blocker
- ORPHENADRINE HYDROCHLORIDE blocker
- PROPAFENONE HYDROCHLORIDE blocker
- DRONEDARONE HYDROCHLORIDE blocker
- RUFINAMIDE blocker
- TETRACAINE HYDROCHLORIDE blocker
- PHENYTOIN blocker
- PHENYTOIN SODIUM blocker
- PROPOXYCAINE HYDROCHLORIDE blocker
- ROPIVACAINE HYDROCHLORIDE blocker
- ENCAINIDE HYDROCHLORIDE blocker
- NERISPIRDINE blocker
- RALFINAMIDE blocker
- TOPIRAMATE blocker
- IRAMPANEL blocker
- ELPETRIGINE blocker
- ESLICARBAZEPINE blocker
- DICHLOROBENZYL ALCOHOL 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
Related proteins · sequence + function similarity
- Sodium channel protein type 3 subunit alpha 0.99
- Sodium channel protein type 2 subunit alpha 0.99
- Sodium channel protein type 3 subunit alpha 0.99
- Sodium channel protein type 2 subunit alpha 0.99
- Sodium channel protein type 2 subunit alpha 0.99
- Sodium channel protein type 8 subunit alpha 0.98
- Sodium channel protein type 8 subunit alpha 0.98
- Sodium channel protein type 8 subunit alpha 0.98
- Sodium channel protein type 9 subunit alpha 0.98
- Sodium channel protein type 9 subunit alpha 0.97
- Sodium channel protein type 9 subunit alpha 0.97
- Sodium channel protein type 1 subunit alpha 0.97
Co-cited proteins · studied together in the literature
- Sodium channel protein type 3 subunit alpha 1 shared papers
- Sodium channel protein type 2 subunit alpha 3 shared papers
- Sodium channel regulatory subunit beta-2 1 shared papers
- Sodium channel regulatory subunit beta-1 1 shared papers
- Sodium channel protein type 2 subunit alpha 2 shared papers
- Sodium channel protein type 1 subunit alpha 2 shared papers
- Sodium channel protein type 5 subunit alpha 1 shared papers
- VIP36-like protein 1 shared papers
- Gamma-aminobutyric acid receptor subunit gamma-3 1 shared papers
- von Willebrand factor A domain-containing protein 3B 1 shared papers
- E3 ubiquitin-protein ligase NEDD4-like 1 shared papers
- Sodium channel protein type 8 subunit alpha 1 shared papers
Literature · 14 cited papers
- Structural basis for modulation of human NaV1.3 by clinical drug and selective antagonist. Nat. Commun. · 2022
- Mutations in SCN3A cause early infantile epileptic encephalopathy. Ann. Neurol. · 2018
- 1.3 is important for enterochromaffin cell excitability and serotonin release. Sci. Rep. · 2017
- SCN3A deficiency associated with increased seizure susceptibility. Neurobiol. Dis. · 2017
- Homozygous missense mutation in the LMAN2L gene segregates with intellectual disability in a large consanguineous Pakistani family. J. Med. Genet. · 2016
- A disulfide tether stabilizes the block of sodium channels by the conotoxin muO[section sign]-GVIIJ. Proc. Natl. Acad. Sci. U.S.A. · 2014
- Novel SCN3A variants associated with focal epilepsy in children. Neurobiol. Dis. · 2014
- Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
- Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins. Am. J. Physiol. · 2005
- Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol. Psychiatry · 2003
- Genomic structures of SCN2A and SCN3A -- candidate genes for deafness at the DFNA16 locus. Gene · 2001
- Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. · 2000
- … and 2 more in the literature graph