SELENON

Protein identityUniProt · HPA

UniProt accession

Q9NZV5

Gene

SELENON

Ensembl

ENSG00000162430

Chromosome

1

Canonical length

590 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Cytosol

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a glycoprotein that is localized in the endoplasmic reticulum. It plays an important role in cell protection against oxidative stress, and in the regulation of redox-related calcium homeostasis. Mutations in this gene are associated with early onset muscle disorders, referred to as SEPN1-related myopathy. SEPN1-related myopathy consists of 4 autosomal recessive disorders, originally thought to be separate entities: rigid spine muscular dystrophy (RSMD1), the classical form of multiminicore disease, desmin related myopathy with Mallory-body like inclusions, and congenital fiber-type disproportion (CFTD). This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. A second stop-codon redefinition element (SRE) adjacent to the UGA codon has been identified in this gene (PMID:15791204). SRE is a phylogenetically conserved stem-loop structure that stimulates readthrough at the UGA codon, and augments the Sec insertion efficiency by SECIS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2016]

Canonical amino-acid sequenceUniProt

590 residues, UniProt reviewed canonical sequence.

>Q9NZV5|SELENON
     1  MGRARPGQRG PPSPGPAAQP PAPPRRRARS LALLGALLAA AAAAAVRVCA RHAEAQAAAR
    61  QELALKTLGT DGLFLFSSLD TDGDMYISPE EFKPIAEKLT GSCSVTQTGV QWCSHSSLQP
   121  QLPWLNUSSC LSLLRSTPAA SCEEEELPPD PSEETLTIEA RFQPLLPETM TKSKDGFLGV
   181  SRLALSGLRN WTAAASPSAV FATRHFQPFL PPPGQELGEP WWIIPSELSM FTGYLSNNRF
   241  YPPPPKGKEV IIHRLLSMFH PRPFVKTRFA PQGAVACLTA ISDFYYTVMF RIHAEFQLSE
   301  PPDFPFWFSP AQFTGHIILS KDATHVRDFR LFVPNHRSLN VDMEWLYGAS ESSNMEVDIG
   361  YIPQMELEAT GPSVPSVILD EDGSMIDSHL PSGEPLQFVF EEIKWQQELS WEEAARRLEV
   421  AMYPFKKVSY LPFTEAFDRA KAENKLVHSI LLWGALDDQS CUGSGRTLRE TVLESSPILT
   481  LLNESFISTW SLVKELEELQ NNQENSSHQK LAGLHLEKYS FPVEMMICLP NGTVVHHINA
   541  NYFLDITSVK PEEIESNLFS FSSTFEDPST ATYMQFLKEG LRRGLPLLQP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SELENON can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0

Highest tissue expression

58 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SELENON.

Disease | AllUniProt

Conditions SELENON is implicated in, by any mechanism.

• Congenital myopathy 3 with rigid spine (CMYO3) MIM:602771

Disease | GeneticClinVar

114 pathogenic / likely-pathogenic of 816 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Eichsfeld type congenital muscular dystrophy
• Congenital myopathy with fiber type disproportion
• Congenital myopathy 4A, autosomal dominant
• SEPN1-related disorder
• See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.02

gnomAD pLI

0

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATP metabolic process
• calcium ion homeostasis
• calcium ion import
• cell redox homeostasis
• cellular response to caffeine
• cellular response to oxidative stress
• collagen fibril organization
• diaphragm contraction
• energy reserve metabolic process
• gene expression
• L-ascorbic acid metabolic process
• L-ascorbic acid transmembrane transport
• lung alveolus development
• membrane biogenesis
• membrane organization
• membrane to membrane docking
• mitochondrial calcium ion transmembrane transport
• mitochondrion organization
• mitochondrion-endoplasmic reticulum membrane tethering
• multicellular organismal response to stress
• positive regulation of response to oxidative stress
• positive regulation of skeletal muscle cell proliferation
• regulation of ryanodine-sensitive calcium-release channel activity
• response to endoplasmic reticulum stress
• response to muscle activity involved in regulation of muscle adaptation
• skeletal muscle fiber development
• skeletal muscle satellite cell differentiation
• skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration
• transforming growth factor beta receptor signaling pathway

Molecular functions

• calcium ion binding
• oxidoreductase activity

Cellular components

• endoplasmic reticulum membrane
• mitochondria-associated endoplasmic reticulum membrane contact site
• mitochondrial membrane

Protein domainsUniProt · Pfam · InterPro

• EF-hand domain

KeywordsUniProt

• Desmin-related myopathy
• Endoplasmic reticulum
• Glycoprotein
• Membrane
• Myofibrillar myopathy
• Oxidoreductase
• Selenocysteine
• Signal

InteractionsUniProt · HPA

Protein binding partners of SELENON in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RYR1
• RYR2
• RYR3