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SCN8A Membrane Protein Introduction

Introduction of SCN8A

SCN8A encodes the sodium channel protein type 8 subunit alpha (SCN8A or Nav1.6). As a member of the voltage-gated sodium (Nav) channel family, SCN8A has the typical structure containing four homologous domains (DI-DIV), each with six highly conserved transmembrane segments designated S1-S6. Less-conserved cytoplasmic loops separate domains DI and DII, domains DII and DIII. Domains III and IV are separated by a short, highly conserved inactivation gate. Voltage sensitivity is provided by positively charged arginine and histidine residues in the fourth transmembrane segments (S4). The channel “fast-inactivates” through a hinged lid mechanism (internal DIII-DIV linker) that occludes the intracellular mouth of the pore (composed of the S5-S6 segments of all four domains). SCN8A is predominantly expressed in neurons, and is one of the most abundant sodium channels in the central nervous system (CNS).

Basic Information of SCN8A
Protein Name Sodium channel protein type 8 subunit alpha
Gene Name SCN8A
Aliases Sodium channel protein type VIII subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.6
Organism Homo sapiens (Human)
UniProt ID Q9UQD0
Transmembrane Times 24
Length (aa) 1980
Sequence MAARLLAPPGPDSFKPFTPESLANIERRIAESKLKKPPKADGSHREDDEDSKPKPNSDLEAGKSLPFIYGDIPQGLVAVPLEDFDPYYLTQKTFVVLNRGKTLFRFSATPALYILSPFNLIRRIAIKILIHSVFSMIIMCTILTNCVFMTFSNPPDWSKNVEYTFTGIYTFESLVKIIARGFCIDGFTFLRDPWNWLDFSVIMMAYITEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCVVWPINFNESYLENGTKGFDWEEYINNKTNFYTVPGMLEPLLCGNSSDAGQCPEGYQCMKAGRNPNYGYTSFDTFSWAFLALFRLMTQDYWENLYQLTLRAAGKTYMIFFVLVIFVGSFYLVNLILAVVAMAYEEQNQATLEEAEQKEAEFKAMLEQLKKQQEEAQAAAMATSAGTVSEDAIEEEGEEGGGSPRSSSEISKLSSKSAKERRNRRKKRKQKELSEGEEKGDPEKVFKSESEDGMRRKAFRLPDNRIGRKFSIMNQSLLSIPGSPFLSRHNSKSSIFSFRGPGRFRDPGSENEFADDEHSTVEESEGRRDSLFIPIRARERRSSYSGYSGYSQGSRSSRIFPSLRRSVKRNSTVDCNGVVSLIGGPGSHIGGRLLPEATTEVEIKKKGPGSLLVSMDQLASYGRKDRINSIMSVVTNTLVEELEESQRKCPPCWYKFANTFLIWECHPYWIKLKEIVNLIVMDPFVDLAITICIVLNTLFMAMEHHPMTPQFEHVLAVGNLVFTGIFTAEMFLKLIAMDPYYYFQEGWNIFDGFIVSLSLMELSLADVEGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKECVCKINQDCELPRWHMHDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDGEMNNLQISVIRIKKGVAWTKLKVHAFMQAHFKQREADEVKPLDELYEKKANCIANHTGADIHRNGDFQKNGNGTTSGIGSSVEKYIIDEDHMSFINNPNLTVRVPIAVGESDFENLNTEDVSSESDPEGSKDKLDDTSSSEGSTIDIKPEVEEVPVEQPEEYLDPDACFTEGCVQRFKCCQVNIEEGLGKSWWILRKTCFLIVEHNWFETFIIFMILLSSGALAFEDIYIEQRKTIRTILEYADKVFTYIFILEMLLKWTAYGFVKFFTNAWCWLDFLIVAVSLVSLIANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKYHYCFNETSEIRFEIEDVNNKTECEKLMEGNNTEIRWKNVKINFDNVGAGYLALLQVATFKGWMDIMYAAVDSRKPDEQPKYEDNIYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPLNKIQGIVFDFVTQQAFDIVIMMLICLNMVTMMVETDTQSKQMENILYWINLVFVIFFTCECVLKMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIFSIFGMSNFAYVKHEAGIDDMFNFETFGNSMICLFQITTSAGWDGLLLPILNRPPDCSLDKEHPGSGFKGDCGNPSVGIFFFVSYIIISFLIVVNMYIAIILENFSVATEESADPLSEDDFETFYEIWEKFDPDATQFIEYCKLADFADALEHPLRVPKPNTIELIAMDLPMVSGDRIHCLDILFAFTKRVLGDSGELDILRQQMEERFVASNPSKVSYEPITTTLRRKQEEVSAVVLQRAYRGHLARRGFICKKTTSNKLENGGTHREKKESTPSTASLPSYDSVTKPEKEKQQRAEEGRRERAKRQKEVRESKC

Function of SCN8A Membrane Protein

SCN8A is abundantly expressed throughout the CNS, with high expression in the cerebellum, hippocampus, cortex and olfactory bulb. Primary motor neurons, as well as cerebellar Purkinje and granule cells, have strong expression of SCN8A, suggesting a role in motor control. SCN8A channels are enriched at the neuronal axon initial segment and nodes of Ranvier, where they promote neuronal excitability by participating in the initiation and propagation of action potentials. SCN8A channels generate persistent current, hyperpolarized thresholds of activation compared with other NaV channels, and resurgent current. These biophysical properties make SCN8A a critical mediator of neuronal excitability. SCN8A mutations have been associated with epilepsy and neurodevelopmental disorders.

Positions of missense mutations of SCN8A in epileptic encephalopathy. Fig.1 Positions of missense mutations of SCN8A in epileptic encephalopathy. (Wagnon, 2015)

Application of SCN8A Membrane Protein in Literature

  1. Larsen J., et al. The phenotypic spectrum of SCN8A encephalopathy. Neurology. 2015, 84(5):480-9. PubMed ID: 25568300

    This article finds that SCN8A encephalopathy presents in infancy with multiple seizure types including focal seizures and spasms in some cases.

  2. Kong W., et al. SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability. Epilepsia. 2015, 56(3):431-8. PubMed ID: 25785782

    This article suggests that SCN8A as an important candidate gene should be detected in patients with epilepsy of unknown etiology and IDDs. An interesting finding is that SCB might provide satisfied efficacy for epileptic seizure in patients with an SCN8A mutation.

  3. Makinson C.D., et al. Role of the hippocampus in Nav1.6 (Scn8a) mediated seizure resistance. Neurobiology of Disease. 2014, 68:16-25. PubMed ID: 24704313

    This article suggests that selective targeting of Scn8a activity might be efficacious in patients with epilepsy.

  4. Wagnon J.L. and Meisler M.H. Recurrent and non-recurrent mutations of SCN8A in epileptic encephalopathy. Frontiers in Neurology. 2015, 6:104. PubMed ID: 26029160

    This article reveals that functional differences among pathogenic mutations of SCN8A will have implications for the selection of treatment for individual patients and for the development of new therapies.

  5. Berghuis B., et al. Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy. Epilepsy Research. 2015, 115:141-4. PubMed ID: 26220391

    This article suggests that complex alterations in the SCN8A gene may underlie epilepsy and cognitive impairment.

SCN8A Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SCN8A antibody development services.


Based on our versatile platform and abundant experience, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

  1. Wagnon J L and Meisler M H. (2015). Recurrent and non-recurrent mutations of SCN8A in epileptic encephalopathy. Frontiers in Neurology. 6: 104.

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