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In-Silico characterization of SCN9A: A protein that mediates voltage-dependent sodium ion permeability of excitable membranes

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Research Paper 01/11/2017
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In-Silico characterization of SCN9A: A protein that mediates voltage-dependent sodium ion permeability of excitable membranes

Humaira Aziz Sawal, Rubina Dad, Sarmad Mehmood, Umme Kalsoom, Peter John, Muhammad Jawad Hassan
Int. J. Biosci.11( 5), 378-385, November 2017.
Certificate: IJB 2017 [Generate Certificate]
Key: CharacterizationCIPCongenital insensitivity to painIn-silicoSCN9A

Abstract

Sodium channel NaV 1.7, SCN9A gene encodes the SCN9A protein which is associated with either pain insensitivity typically with loss-of-function mutations, and chronic pain disorders typical with gain-of-function mutations. In the present study, we tried to characterize the SCN9A structure and predict its interactions with different proteins using different on-line tools. Protscale server predicted an unstable protein structure for SCN9A based on several parameters including accessibility, hydrophilicity, mutability, refractivity bulkiness, flexibility and polarity. Signal Server predicted no signal peptide in SCN9A. No acetylation site was present in SCN9A: as predicted by Net Acet. Different threonine, serine and tyrosine specific phosphorylation sites were predicted in SCN9A at different positions. Kinases like PKA and PKC were shown to be involved in phosphorylation of SCN9A. We also predicted different physiochemical parameters for SCN9A. The study also predicted that SCN9A might interact with other members of sodium channel family including SCN2A, SCN3A, SCN5A, SCN8A, SCN10A, SCN11A, SCN1B, SCN2B, SCN4B ABCB1 and CALM2 proteins. These results might be helpful to understand disease pathogenesis and molecular mechanisms of different inherited disorders of nervous system including congenital sensitivity to pain caused by SCN9A mutations.

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Baker MD and Wood JN. 2001. Involvement of Na+ channels in pain pathways. Trends in pharma cological sciences 22(1), 27-31.

Chen YH, Dale TJ, Romanos MA, Whitaker WRJ, Xie XM, Clare JJ. 2000. Cloning, distribution and functional analysis of the type III sodium channel from human brain. European. Journal of neurosciences 12, 4281-4289.

Cole C, Barber JD, Barton GJ. 2008. The Jpred 3 secondary structure prediction server. Nucleic acids research 36(suppl 2), W197-W201.

Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L. Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods, CG. 2006. An SCN9A channelopathy causes congenital inability to experience pain. Nature 444, 894-898.

de Lera Ruiz M Kraus RL. 2015. Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications. Journal of medical chemistry 58(18), 7093-118. DOI: 10.1021/ jm501981g.

Dehen H, Willer JC, Boureau F, Cambier J. 1977. Congenital insensitivity to pain, and endogenous morphine-like substances. Lancet 2(8032), 293-294.

Dyck PJ, Mellinger JF, Reagan TJ, Horowitz SJ, McDonald JW, Litchy WJ, Daube JR, Fealey RD, Go VL, Kao PC, Brimijoin WS, Lambert EH. 1983. Not ‘indifference to pain’ but varieties of hereditary sensory and autonomic neuropathy. Brain 106(Pt 2), 373-390.

Garnier J, Gibrat JF, Robson B. 1996. GOR method for predicting protein secondary structure from amino acid sequence. Methods in enzymology 266, 540-553.

Goldberg YP, Pimstone SN,Namdari R, Price N, Cohen C, Sherrington RP, Hayden MR. 2012. Human Mendelian pain disorders: A key to discovery and validation of novel analgesics. Clinical genetics 82(4), 367-373.

Juan JJ, Julián PD, Ángeles O, Rosa MR, Francesca P, Mar Rodríguez-Vázquez del R, Martín OG, Lorenzo M, Roberto BV, Enrique B,Miguel ÁLT. 2016. Calmodulin 2 mutation N98S is associated with unexplained cardiac arrest in infants due to low clinical penetrance electrical disorders. PLoS one. 11(4), e0153851. DOI: 10.1371/ journal.pone.0153851

Keller DI, Huang H, Zhao J, Frank R, Suarez V, Delacrétaz E, Brink M, Osswald S, Schwick N, Chahine M. 2006. A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation. Cardiovascular research 70(3), 521-529.

Michiels JJ, te Morsche RHM, Jansen JBMJ Drenth JPH. 2005. Autosomal dominant erythermalgia associated with a novel mutation in the voltage-gated sodium channel alpha-subunit. Archive of neurology. 62, 587-1590.

Raymond CK, Castle J, Garrett-Engele P, Armour CD, Kan Z, Tsinoremas N, Johnson JM. 2004. Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia. J of biological chemistry 279(44), 46234-46241.

St. John Smith E, Omerbasic D, Lechner SG, Anirudhan G. Lapatsina L, Lewin GR. 2011. The molecular basis of acid insensitivity in the African naked mole-rat. Science 334, 1557-1560.

Striano P, Bordo L, Lispi ML, Specchio N, Minetti C, Vigevano F, Zara F. 2006. A novel SCN2A mutation in family with benign familial infantile seizures. Epilepsia 47(1), 218-220.

Trudeau MM, Dalton JC, Day JW, Ranum LP, Meisler MH. 2006. Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation. Journal of medical genetics. 43(6), 527-530.

Yang Y, Wang Y, Li S, Xu Z, Li H, Ma L, Fan J, Bu D, Liu B, Fan Z, Wu G, Jin J, Ding B, Zhu X, Shen Y. 2004. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. Journal of medical genetics 41, 171-174.

Zhang Y, Haga N. 2014. Skeletal complications in congenital insensitivity to pain with anhidrosis: A case series of 14 patients and review of articles published in Japanese. Journal of orthopaedic science 19(5), 827-831.

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