SCN8A

Sodium channel, voltage gated, type VIII alpha subunit

PDB rendering based on 1byy.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1byy

Identifiers

Symbols

SCN8A ; CERIII; CIAT; EIEE13; MED; NaCh6; Nav1.6; PN4

External IDs

OMIM: 600702 MGI: 103169 HomoloGene: 7927 IUPHAR: 583 ChEMBL: 5202 GeneCards: SCN8A Gene

Gene ontology
Molecular function	• voltage-gated sodium channel activity • ATP binding
Cellular component	• voltage-gated sodium channel complex • plasma membrane • integral component of membrane • cytoplasmic membrane-bounded vesicle • Z disc • dendrite • node of Ranvier • neuronal cell body • axon initial segment
Biological process	• sodium ion transport • nervous system development • peripheral nervous system development • muscle organ development • sensory perception of sound • adult walking behavior • response to toxic substance • neuronal action potential • regulation of ion transmembrane transport • sodium ion transmembrane transport • myelination • neuromuscular process • membrane depolarization during action potential
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
51.59 – 51.81 Mb

Chr 15:
100.87 – 101.05 Mb

PubMed search

Sodium channel, voltage gated, type VIII, alpha subunit also known as SCN8A or Na_v1.6 is a protein which in humans is encoded by the SCN8A gene.^[1] It is a voltage-gated sodium channel.

The ion channel was discovered by John Caldwell and colleagues at the University of Colorado Health Sciences Center in the rat,^[2] and by Miriam Meisler and colleagues at the University of Michigan Medical School in the mouse.^[3]

Mutations in this gene have been associated to cases of early infantile epileptic encephalopathy (PMID 24352161). The first known mutation in humans was a missense (c.5302A>G [p.Asn1768Asp]) mutation discovered by Krishna Veeramah and Michael Hammer at the University of Arizona.^[4]

An SCN8A Website and Registry has been established at the University of Arizona and approved by the Institutional Review Board for collecting information from families about SCN8A-related epilepsy (http://www.scn8a.net).

References

↑ "Entrez Gene: SCN8A sodium channel, voltage gated, type VIII, alpha subunit".
↑ "A novel, abundant sodium channel expressed in neurons and glia.". The Journal of Neuroscience. Retrieved 2010-11-22.
↑ "Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'". Nature Genetics. Retrieved 2010-11-22.
↑ "De Novo Pathogenic SCN8A Mutation Identified by Whole-Genome Sequencing of a Family Quartet Affected by Infantile Epileptic Encephalopathy and SUDEP". "The American Journal of Human Genetics". Retrieved 2015-09-24.

Catterall WA, Goldin AL, Waxman SG (2006). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.". Pharmacol. Rev. 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098.
Burgess DL, Kohrman DC, Galt J, et al. (1995). "Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'". Nat. Genet. 10 (4): 461–5. doi:10.1038/ng0895-461. PMID 7670495.
Plummer NW, McBurney MW, Meisler MH (1997). "Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells". J. Biol. Chem. 272 (38): 24008–15. doi:10.1074/jbc.272.38.24008. PMID 9295353.
Plummer NW, Galt J, Jones JM, et al. (1999). "Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A". Genomics 54 (2): 287–96. doi:10.1006/geno.1998.5550. PMID 9828131.
Anis Y, Nürnberg B, Visochek L, et al. (1999). "Activation of Go-proteins by membrane depolarization traced by in situ photoaffinity labeling of galphao-proteins with [alpha32P]GTP-azidoanilide". J. Biol. Chem. 274 (11): 7431–40. doi:10.1074/jbc.274.11.7431. PMID 10066808.
Caldwell JH, Schaller KL, Lasher RS, et al. (2000). "Sodium channel Nav1.6 is localized at nodes of Ranvier, dendrites, and synapses". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5616–20. doi:10.1073/pnas.090034797. PMC 25877. PMID 10779552.
Wittmack EK, Rush AM, Craner MJ, et al. (2005). "Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons". J. Neurosci. 24 (30): 6765–75. doi:10.1523/JNEUROSCI.1628-04.2004. PMID 15282281.
Raymond CK, Castle J, Garrett-Engele P, et al. (2004). "Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia". J. Biol. Chem. 279 (44): 46234–41. doi:10.1074/jbc.M406387200. PMID 15302875.
Drews VL, Lieberman AP, Meisler MH (2005). "Multiple transcripts of sodium channel SCN8A (Na(V)1.6) with alternative 5'- and 3'-untranslated regions and initial characterization of the SCN8A promoter". Genomics 85 (2): 245–57. doi:10.1016/j.ygeno.2004.09.002. PMID 15676283.
Wittmack EK, Rush AM, Hudmon A, et al. (2006). "Voltage-gated sodium channel Nav1.6 is modulated by p38 mitogen-activated protein kinase". J. Neurosci. 25 (28): 6621–30. doi:10.1523/JNEUROSCI.0541-05.2005. PMID 16014723.
Schiavon E, Sacco T, Cassulini RR, et al. (2006). "Resurgent current and voltage sensor trapping enhanced activation by a beta-scorpion toxin solely in Nav1.6 channel. Significance in mice Purkinje neurons". J. Biol. Chem. 281 (29): 20326–37. doi:10.1074/jbc.M600565200. PMID 16702217.
Shirahata E, Iwasaki H, Takagi M, et al. (2006). "Ankyrin-G regulates inactivation gating of the neuronal sodium channel, Nav1.6". J. Neurophysiol. 96 (3): 1347–57. doi:10.1152/jn.01264.2005. PMID 16775201.
Black JA, Newcombe J, Trapp BD, Waxman SG (2007). "Sodium channel expression within chronic multiple sclerosis plaques". J. Neuropathol. Exp. Neurol. 66 (9): 828–37. doi:10.1097/nen.0b013e3181462841. PMID 17805013.

PDB gallery

1byy: SODIUM CHANNEL IIA INACTIVATION GATE

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia - version of the Tuesday, May 03, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

SCN8A

See also

References

Further reading