Selenoprotein N

Definition:

[Isoform 2]: Plays an important role in cell protection against oxidative stress and in the regulation of redox-related calcium homeostasis. Regulates the calcium level of the ER by protecting the calcium pump ATP2A2 against the oxidoreductase ERO1A-mediated oxidative damage. Within the ER, ERO1A activity increases the concentration of H(2)O(2), which attacks the luminal thiols in ATP2A2 and thus leads to cysteinyl sulfenic acid formation (-SOH) and SEPN1 reduces the SOH back to free thiol (-SH), thus restoring ATP2A2 activity. Acts as a modulator of ryanodine receptor (RyR) activity: protects RyR from oxidation due to increased oxidative stress, or directly controls the RyR redox state, regulating the RyR-mediated calcium mobilization required for normal muscle development and differentiation.; Essential for muscle regeneration and satellite cell maintenance in skeletal muscle.

References:

[1]. Sandrine Arbogast, et al. Oxidative stress in SEPN1-related myopathy: from pathophysiology to treatment. Ann Neurol. 2009 Jun;65(6):677-86. [Content Brief]

[2]. Perrine Castets, et al. Satellite cell loss and impaired muscle regeneration in selenoprotein N deficiency. Hum Mol Genet. 2011 Feb 15;20(4):694-704. [Content Brief]

[3]. Michael J Jurynec, et al. Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12485-90. [Content Brief]

[4]. Marianna Marino, et al. SEPN1, an endoplasmic reticulum-localized selenoprotein linked to skeletal muscle pathology, counteracts hyperoxidation by means of redox-regulating SERCA2 pump activity. Hum Mol Genet. 2015 Apr 1;24(7):1843-55. [Content Brief]

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