SMN2
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| PDB 1g5v | |
Supervivencia de motoneurona 2, centromérica
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| Identificadores | |
| Símbolo | SMN2 |
| Símbolos alt. | BCD541; C-BCD541; GEMIN1; SMNC; TDRD16B |
| Entrez | 6607 |
| OMIM | |
| RefSeq | NP_059107 |
| UniProt | Q16637 |
| Outros datos | |
| Locus | Cr. 5 :(69.35 – 69.37 Mb) |
A proteína supervivencia de motoneurona 2, centromérica abreviada como SMN2 é unha proteína que nos humanos está codificada polo xene SMN2 do cromosoma 5.[1][2]
Xene
[editar | editar a fonte]O xene está situado no cromosoma 5 e ten unha variante telomérica chamada SMN1, e unha variante centromérica, que é o SMN2. Nótese que non están no centrómero e no telómero, senón na metade en dirección ao telómero e na metade en dirección ao centrómero dunha rexión con duplicacións invertidas de organización complexa do cromosoma 5, onde se atopan ditos xenes. As copias teloméricas (SMN1) e centroméricas (SMN2) deste xene son case idénticas (diferéncianse nun nucleótido no exón 7) e codifican a mesma proteína, pero mentres que as mutacións na variante telomérica están asociadas coa atrofia muscular espiñal, as da variante centromérica non. O exón 7 crese que é un amplificador de splicing do exón. Os nove exóns presentes neste xene, tanto na copia telomérica coma na centromérica designáronse historicamente como exón 1, 2a, 2b, e 3-8. Ambos os xenes poden estar implicados en conversións xénicas, o que fai que varíe o número de copias de cada xene.[2]
Función
[editar | editar a fonte]A proteína codificada polo xene encóntrase no núcleo e no citoplasma. No núcleo está asociado aos corpos subnucleares chamados GEMS, que están próximos aos corpos de Cajal, e conteñen snRNPs. Asóciase formando complexos con diversas proteínas como SIP1, GEMIN4, e a proteína hnRNP U e outras. Describíronse catro variantes de transcrición que dan lugar a distintas isoformas.[2]
Notas
[editar | editar a fonte]- ↑ Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M (January 1995). "Identification and characterization of a spinal muscular atrophy-determining gene". Cell 80 (1): 155–65. PMID 7813012. doi:10.1016/0092-8674(95)90460-3.
- ↑ 2,0 2,1 2,2 "Entrez Gene: survival of motor neuron 2, centromeric".
Véxase tamén
[editar | editar a fonte]Outros artigos
[editar | editar a fonte]Bibliografía
[editar | editar a fonte]- Watihayati MS, Fatemeh H, Marini M; et al. (2009). "Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy.". Brain Dev. 31 (1): 42–5. PMID 18842367. doi:10.1016/j.braindev.2008.08.012.
- Prior TW, Krainer AR, Hua Y; et al. (2009). "A positive modifier of spinal muscular atrophy in the SMN2 gene.". Am. J. Hum. Genet. 85 (3): 408–13. PMC 2771537. PMID 19716110. doi:10.1016/j.ajhg.2009.08.002.
- Coady TH, Baughan TD, Shababi M; et al. (2008). Valcarcel, Juan, ed. "Development of a single vector system that enhances trans-splicing of SMN2 transcripts.". PLoS ONE 3 (10): e3468. PMC 2565107. PMID 18941511. doi:10.1371/journal.pone.0003468.
- Elsheikh B, Prior T, Zhang X; et al. (2009). "An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy.". Muscle Nerve 40 (4): 652–6. PMID 19760790. doi:10.1002/mus.21350.
- Workman E, Saieva L, Carrel TL; et al. (2009). "A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice.". Hum. Mol. Genet. 18 (12): 2215–29. PMC 2685758. PMID 19329542. doi:10.1093/hmg/ddp157.
- Bose JK, Wang IF, Hung L; et al. (2008). "TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing.". J. Biol. Chem. 283 (43): 28852–9. PMC 2661999. PMID 18703504. doi:10.1074/jbc.M805376200.
- Hauke J, Riessland M, Lunke S; et al. (2009). "Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition.". Hum. Mol. Genet. 18 (2): 304–17. PMC 2638778. PMID 18971205. doi:10.1093/hmg/ddn357.
- Corcia P, Camu W, Praline J; et al. (2009). "The importance of the SMN genes in the genetics of sporadic ALS.". Amyotroph Lateral Scler 10 (5-6): 436–40. PMID 19922137. doi:10.3109/17482960902759162.
- Tiziano FD, Pinto AM, Fiori S; et al. (2010). "SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR.". Eur. J. Hum. Genet. 18 (1): 52–8. PMC 2987170. PMID 19603064. doi:10.1038/ejhg.2009.116.
- Jedrzejowska M, Milewski M, Zimowski J; et al. (2009). "Phenotype modifiers of spinal muscular atrophy: the number of SMN2 gene copies, deletion in the NAIP gene and probably gender influence the course of the disease.". Acta Biochim. Pol. 56 (1): 103–8. PMID 19287802.
- Arkblad E, Tulinius M, Kroksmark AK; et al. (2009). "A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy.". Acta Paediatr. 98 (5): 865–72. PMID 19154529. doi:10.1111/j.1651-2227.2008.01201.x.
- Paushkin S, Gubitz AK, Massenet S, Dreyfuss G (2002). "The SMN complex, an assemblyosome of ribonucleoproteins.". Curr. Opin. Cell Biol. 14 (3): 305–12. PMID 12067652. doi:10.1016/S0955-0674(02)00332-0.
- Farooq F, Balabanian S, Liu X; et al. (2009). "p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR.". Hum. Mol. Genet. 18 (21): 4035–45. PMID 19648294. doi:10.1093/hmg/ddp352.
- Hasanzad M, Golkar Z, Kariminejad R; et al. (2009). "Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy.". Ann. Acad. Med. Singap. 38 (2): 139–41. PMID 19271042.
- Martins de Araújo M, Bonnal S, Hastings ML; et al. (2009). "Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP.". RNA 15 (4): 515–23. PMC 2661831. PMID 19244360. doi:10.1261/rna.1273209.
- Song F, Qu YJ, Zou LP; et al. (2008). "[Molecular analysis of survival motor neuron gene in 338 suspicious children patients with spinal muscular atrophy]". Zhonghua Er Ke Za Zhi 46 (12): 919–23. PMID 19134255.
- Irimura S, Kitamura K, Kato N; et al. (2009). "HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1.". The Kobe journal of medical sciences 54 (5): E227–36. PMID 19628962.
- Yong J, Wan L, Dreyfuss G (2004). "Why do cells need an assembly machine for RNA-protein complexes?". Trends Cell Biol. 14 (5): 226–32. PMID 15130578. doi:10.1016/j.tcb.2004.03.010.
- Chen HH, Chang JG, Lu RM; et al. (2008). "The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene.". Mol. Cell. Biol. 28 (22): 6929–38. PMC 2573304. PMID 18794368. doi:10.1128/MCB.01332-08.
- Cogulu O, Durmaz B, Pehlivan S; et al. (2009). "Evaluation of the SMN and NAIP genes in a family: homozygous deletion of the SMN2 gene in the fetus and outcome of the pregnancy.". Genet Test Mol Biomarkers 13 (3): 287–8. PMID 19397406. doi:10.1089/gtmb.2008.0139.