SEPN1
| Selenoprotein N, 1 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||
| Symbols | SEPN1 ; CFTD; MDRS1; RSMD1; RSS; SELN | ||||||||||||
| External IDs | OMIM: 606210 HomoloGene: 10723 GeneCards: SEPN1 Gene | ||||||||||||
| |||||||||||||
| 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: 26.13 – 26.14 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
| 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 Sepn1tm1a(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
- ↑ Lescure A, Gautheret D, Carbon P, Krol A (Feb 2000). "Novel selenoproteins identified in silico and in vivo by using a conserved RNA structural motif". J Biol Chem 274 (53): 38147–54. doi:10.1074/jbc.274.53.38147. PMID 10608886.
- ↑ 2.0 2.1 "Entrez Gene: SEPN1 selenoprotein N, 1".
- ↑ "Radiography data for Sepn1". Wellcome Trust Sanger Institute.
- ↑ "Salmonella infection data for Sepn1". Wellcome Trust Sanger Institute.
- ↑ "Citrobacter infection data for Sepn1". Wellcome Trust Sanger Institute.
- ↑ 6.0 6.1 6.2 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.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Further reading
- Aho H, Schwemmer M, Tessman D et al. (1997). "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 et al. (1998). "Identification of a new locus for a peculiar form of congenital muscular dystrophy with early rigidity of the spine, on chromosome 1p35-36.". Am. J. Hum. Genet. 62 (6): 1439–45. doi:10.1086/301882. PMC 1377161. PMID 9585610.
- Moghadaszadeh B, Petit N, Jaillard C et al. (2001). "Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome.". Nat. Genet. 29 (1): 17–8. doi:10.1038/ng713. PMID 11528383.
- Ferreiro A, Quijano-Roy S, Pichereau C et al. (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.". Am. J. Hum. Genet. 71 (4): 739–49. doi:10.1086/342719. PMC 378532. PMID 12192640.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Petit N, Lescure A, Rederstorff M et al. (2003). "Selenoprotein N: an endoplasmic reticulum glycoprotein with an early developmental expression pattern.". Hum. Mol. Genet. 12 (9): 1045–53. doi:10.1093/hmg/ddg115. PMID 12700173.
- Ferreiro A, Ceuterick-de Groote C, Marks JJ et al. (2004). "Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene.". Ann. Neurol. 55 (5): 676–86. doi:10.1002/ana.20077. PMID 15122708.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Venance SL, Koopman WJ, Miskie BA et al. (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 (2005). "Early onset myopathy with a novel mutation in the Selenoprotein N gene (SEPN1).". Neuromuscul. Disord. 15 (4): 299–302. doi:10.1016/j.nmd.2004.11.004. PMID 15792869.
- D'Amico A, Haliloglu G, Richard P et al. (2005). "Two patients with 'Dropped head syndrome' due to mutations in LMNA or SEPN1 genes.". Neuromuscul. Disord. 15 (8): 521–4. doi:10.1016/j.nmd.2005.03.006. PMID 15961312.
- Clarke NF, Kidson W, Quijano-Roy S et al. (2006). "SEPN1: associated with congenital fiber-type disproportion and insulin resistance.". Ann. Neurol. 59 (3): 546–52. doi:10.1002/ana.20761. PMID 16365872.
- Allamand V, Richard P, Lescure A et al. (2006). "A single homozygous point mutation in a 3'untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy.". EMBO Rep. 7 (4): 450–4. doi:10.1038/sj.embor.7400648. PMC 1456920. PMID 16498447.
- Gregory SG, Barlow KF, McLay KE et al. (2006). "The DNA sequence and biological annotation of human chromosome 1.". Nature 441 (7091): 315–21. doi:10.1038/nature04727. PMID 16710414.
- Okamoto Y, Takashima H, Higuchi I et al. (2007). "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.