SELENON
Domain
Isoform 2
The N-terminus (first 61 amino acids) contains an endoplasmic reticulum addressing and retention targeting signal.
Function
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 (PubMed:25452428). 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 (PubMed:18713863, PubMed:19557870).
Essential for muscle regeneration and satellite cell maintenance in skeletal muscle (PubMed:21131290).
Involvement in disease
Congenital myopathy 3 with rigid spine
CMYO3
An autosomal recessive, slowly progressive muscular disorder apparent from birth or early childhood and characterized by hypotonia, proximal muscle weakness, poor axial muscle strength, scoliosis and neck weakness, and a variable degree of spinal rigidity. Most patients remain ambulatory. Early ventilatory insufficiency may lead to death by respiratory failure. Additional features may include facial muscle weakness, amyotrophy, joint contractures, distal hyperlaxity, pulmonary hypertension with secondary cardiac dysfunction, and insulin resistance in patients with a low BMI. Skeletal muscle biopsy typically shows multiminicores and other abnormal non-specific myopathic findings.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Isoform 2
N-glycosylated.
Tissue Specificity
Isoform 1 and isoform 2 are expressed in skeletal muscle, brain, lung and placenta. Isoform 2 is also expressed in heart, diaphragm and stomach.
Cellular localization
- Isoform 2
- Endoplasmic reticulum membrane
Alternative names
SELN, SEPN1, SELENON, Selenoprotein N, SelN