SEPN1

Selenoprotein N, 1
Identifiers
Symbols	SEPN1 ; CFTD; MDRS1; RSMD1; RSS; SELN
External IDs	OMIM: 606210 HomoloGene: 10723 GeneCards: SEPN1 Gene
Gene ontology Molecular function • molecular_function • calcium ion binding • protein binding Cellular component • endoplasmic reticulum membrane Biological process • respiratory system process • mitochondrion organization • biological_process • skeletal muscle satellite cell differentiation • positive regulation of skeletal muscle cell proliferation • response to muscle activity involved in regulation of muscle adaptation • multicellular organismal response to stress • cellular response to oxidative stress • skeletal muscle tissue regeneration • lung alveolus development • skeletal muscle fiber development • cellular response to caffeine Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57190	74777
Ensembl	ENSG00000162430	ENSMUSG00000050989
UniProt	Q9NZV5	Q80UX9
RefSeq (mRNA)	NM_020451	NM_029100
RefSeq (protein)	NP_065184	NP_083376
Location (UCSC)	Chr 1: 25.8 – 25.82 Mb	Chr 4: 134.54 – 134.55 Mb
PubMed search

Selenoprotein N is a protein that in humans is encoded by the SEPN1 gene.^[1][2]

Function

This gene encodes a selenoprotein, which contains a selenocysteine (Sec) residue at its active site. The selenocysteine is encoded by the UGA codon that normally signals translation termination. The 3' UTR of selenoprotein genes have a common stem-loop structure, the sec insertion sequence (SECIS), that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Mutations in this gene cause the classical phenotype of multiminicore disease and congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.^[2]

Model organisms

Sepn1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Abnormal[3]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[4]
Citrobacter infection	Normal[5]
All tests and analysis from[6][7]

Model organisms have been used in the study of SEPN1 function. A conditional knockout mouse line, called Sepn1^{tm1a(KOMP)Wtsi[8][9]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] Twenty five tests were carried out on homozygous mutant mice and one significant abnormality was observed: than animals displayed vertebral fusion.^[6]

References

1. Lescure A, Gautheret D, Carbon P, Krol A (Dec 1999). "Novel selenoproteins identified in silico and in vivo by using a conserved RNA structural motif". The Journal of Biological Chemistry 274 (53): 38147–54. doi:10.1074/jbc.274.53.38147. PMID 10608886.
2. "Entrez Gene: SEPN1 selenoprotein N, 1".
3. "Radiography data for Sepn1". Wellcome Trust Sanger Institute.
4. "Salmonella infection data for Sepn1". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Sepn1". Wellcome Trust Sanger Institute.
6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
13. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Aho H, Schwemmer M, Tessman D, Murphy D, Mattei G, Engel W, Adham IM (Mar 1996). "Isolation, expression, and chromosomal localization of the human mitochondrial capsule selenoprotein gene (MCSP)". Genomics 32 (2): 184–90. doi:10.1006/geno.1996.0104. PMID 8833144.
• Moghadaszadeh B, Desguerre I, Topaloglu H, Muntoni F, Pavek S, Sewry C, Mayer M, Fardeau M, Tomé FM, Guicheney P (Jun 1998). "Identification of a new locus for a peculiar form of congenital muscular dystrophy with early rigidity of the spine, on chromosome 1p35-36". American Journal of Human Genetics 62 (6): 1439–45. doi:10.1086/301882. PMC 1377161. PMID 9585610.
• Moghadaszadeh B, Petit N, Jaillard C, Brockington M, Quijano Roy S, Merlini L, Romero N, Estournet B, Desguerre I, Chaigne D, Muntoni F, Topaloglu H, Guicheney P (Sep 2001). "Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome". Nature Genetics 29 (1): 17–8. doi:10.1038/ng713. PMID 11528383.
• Ferreiro A, Quijano-Roy S, Pichereau C, Moghadaszadeh B, Goemans N, Bönnemann C, Jungbluth H, Straub V, Villanova M, Leroy JP, Romero NB, Martin JJ, Muntoni F, Voit T, Estournet B, Richard P, Fardeau M, Guicheney P (Oct 2002). "Mutations of the selenoprotein N gene, which is implicated in rigid spine muscular dystrophy, cause the classical phenotype of multiminicore disease: reassessing the nosology of early-onset myopathies". American Journal of Human Genetics 71 (4): 739–49. doi:10.1086/342719. PMC 378532. PMID 12192640.
• Petit N, Lescure A, Rederstorff M, Krol A, Moghadaszadeh B, Wewer UM, Guicheney P (May 2003). "Selenoprotein N: an endoplasmic reticulum glycoprotein with an early developmental expression pattern". Human Molecular Genetics 12 (9): 1045–53. doi:10.1093/hmg/ddg115. PMID 12700173.
• Ferreiro A, Ceuterick-de Groote C, Marks JJ, Goemans N, Schreiber G, Hanefeld F, Fardeau M, Martin JJ, Goebel HH, Richard P, Guicheney P, Bönnemann CG (May 2004). "Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene". Annals of Neurology 55 (5): 676–86. doi:10.1002/ana.20077. PMID 15122708.
• Venance SL, Koopman WJ, Miskie BA, Hegele RA, Hahn AF (Jan 2005). "Rigid spine muscular dystrophy due to SEPN1 mutation presenting as cor pulmonale". Neurology 64 (2): 395–6. doi:10.1212/01.WNL.0000149755.85666.DB. PMID 15668457.
• Tajsharghi H, Darin N, Tulinius M, Oldfors A (Apr 2005). "Early onset myopathy with a novel mutation in the Selenoprotein N gene (SEPN1)". Neuromuscular Disorders 15 (4): 299–302. doi:10.1016/j.nmd.2004.11.004. PMID 15792869.
• D'Amico A, Haliloglu G, Richard P, Talim B, Maugenre S, Ferreiro A, Guicheney P, Menditto I, Benedetti S, Bertini E, Bonne G, Topaloglu H (Aug 2005). "Two patients with 'Dropped head syndrome' due to mutations in LMNA or SEPN1 genes". Neuromuscular Disorders 15 (8): 521–4. doi:10.1016/j.nmd.2005.03.006. PMID 15961312.
• Clarke NF, Kidson W, Quijano-Roy S, Estournet B, Ferreiro A, Guicheney P, Manson JI, Kornberg AJ, Shield LK, North KN (Mar 2006). "SEPN1: associated with congenital fiber-type disproportion and insulin resistance". Annals of Neurology 59 (3): 546–52. doi:10.1002/ana.20761. PMID 16365872.
• Allamand V, Richard P, Lescure A, Ledeuil C, Desjardin D, Petit N, Gartioux C, Ferreiro A, Krol A, Pellegrini N, Urtizberea JA, Guicheney P (Apr 2006). "A single homozygous point mutation in a 3'untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy". EMBO Reports 7 (4): 450–4. doi:10.1038/sj.embor.7400648. PMC 1456920. PMID 16498447.
• Okamoto Y, Takashima H, Higuchi I, Matsuyama W, Suehara M, Nishihira Y, Hashiguchi A, Hirano R, Ng AR, Nakagawa M, Izumo S, Osame M, Arimura K (Jul 2006). "Molecular mechanism of rigid spine with muscular dystrophy type 1 caused by novel mutations of selenoprotein N gene". Neurogenetics 7 (3): 175–83. doi:10.1007/s10048-006-0046-0. PMID 16779558.

External links

• GeneReviews/NCBI/NIH/UW entry on Congenital Muscular Dystrophy Overview
• GeneReviews/NCBI/NIH/UW entry on Multiminicore Disease