Sodium channel protein type 9 subunit alpha
Also known as: NENA, SCN9A
Function
Pore-forming subunit of Nav1.7, 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. Nav1.7 plays a crucial role in controlling the excitability and action potential propagation from nociceptor neurons, thereby contributing to the sensory perception of pain.
Classification
- Family (Pfam)
- PF00520 Ion_trans, PF24609 IQ_SCN5A_C, PF06512 Na_trans_assoc, PF11933 Na_trans_cytopl
- InterPro
- Ion_trans_dom, IQ_motif_EF-hand-BS, 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 · 41
- 5EK0 X-ray 3.53A
- 6J8G EM 3.20A
- 6J8H EM 3.20A
- 6J8I EM 3.20A
- 6J8J EM 3.20A
- 6N4Q EM 3.60A
- 6N4R EM 4.20A
- 6NT3 EM 3.40A
- 6NT4 EM 3.50A
- 6VXO EM 3.50A
- 6W6O EM 3.20A
- 7K48 EM 3.60A
- … and 29 more
A predicted model is available from AlphaFold.
Gene Ontology · 15
- GO:0030424 axon
- GO:0043679 axon terminus
- GO:0033268 node of Ranvier
- GO:0005886 plasma membrane
- GO:0001518 voltage-gated sodium channel complex
- GO:0005248 voltage-gated sodium channel activity
- GO:0098870 action potential propagation
- GO:0086002 cardiac muscle cell action potential involved in contraction
- GO:0007623 circadian rhythm
- GO:0050974 detection of mechanical stimulus involved in sensory perception
- GO:0050965 detection of temperature stimulus involved in sensory perception of pain
- GO:0086010 membrane depolarization during action potential
- GO:0019228 neuronal action potential
- GO:0019233 sensory perception of pain
- GO:0035725 sodium ion transmembrane transport
Disease associations
- primary erythermalgia MONDO:0007571
- paroxysmal extreme pain disorder MONDO:0008179
- channelopathy-associated congenital insensitivity to pain, autosomal recessive MONDO:0009459
Drugs targeting this protein · 58
- 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
- PF-05089771 blocker
- IRAMPANEL blocker
- ESLICARBAZEPINE blocker
- DICHLOROBENZYL ALCOHOL blocker
- VIXOTRIGINE blocker
- EVENAMIDE blocker
- QUINIDINE SULFATE blocker
- CENOBAMATE inhibitor
- DSP-2230 blocker
- 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 9 subunit alpha 0.99
- Sodium channel protein type 9 subunit alpha 0.99
- Sodium channel protein type 9 subunit alpha 0.99
- Sodium channel protein type 1 subunit alpha 0.98
- Sodium channel protein type 1 subunit alpha 0.98
- Sodium channel protein type 3 subunit alpha 0.98
- Sodium channel protein type 1 subunit alpha 0.98
- Sodium channel protein type 2 subunit alpha 0.98
- Sodium channel protein type 2 subunit alpha 0.98
- Sodium channel protein type 8 subunit alpha 0.98
- Sodium channel protein type 3 subunit alpha 0.98
- Sodium channel protein type 2 subunit alpha 0.98
Co-cited proteins · studied together in the literature
- Alpha-toxin CvIV4 1 shared papers
- Sodium channel protein type 11 subunit alpha 1 shared papers
- Sodium channel protein type 9 subunit alpha 2 shared papers
- Huwentoxin-IV 3 shared papers
- Sodium channel protein type 4 subunit alpha 3 shared papers
- Mu-theraphotoxin-Hsp1a 1 shared papers
- Alpha-mammal toxin AaH2 1 shared papers
- Sodium channel protein type 9 subunit alpha 2 shared papers
- Beta/omega-theraphotoxin-Tp2a 3 shared papers
- Sodium channel regulatory subunit beta-1 2 shared papers
- Beta/delta-theraphotoxin-Pre1a 1 shared papers
- Beta-theraphotoxin-Gr1b 1 shared papers
Literature · 38 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
- Dissection of the structure-function relationship of Nav channels. Proc. Natl. Acad. Sci. U.S.A. · 2024
- Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function. Nat. Commun. · 2023
- No association between SCN9A and monogenic human epilepsy disorders. PLoS Genet. · 2020
- Fluorescence imaging of peripheral nerves by a Nav1.7-targeted inhibitor cystine knot peptide. Bioconj. Chem. · 2019
- Defining the Functional Role of NaV1.7 in Human Nociception. Neuron · 2019
- Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. Science · 2019
- Structural basis of alpha-scorpion toxin action on Nav channels. Science · 2019
- Structural basis of Nav1.7 inhibition by a gating-modifier spider toxin. Cell · 2019
- The tarantula toxin beta/delta-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity. Sci. Rep. · 2017
- Structural basis of Nav1.7 inhibition by an isoform-selective small-molecule antagonist. Science · 2015
- p.L1612P, a novel voltage-gated sodium channel Nav1.7 mutation inducing a cold sensitive paroxysmal extreme pain disorder. Anesthesiology · 2015
- … and 26 more in the literature graph