SMN1
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| PDB 1g5v | |
Supervivencia de motoneurona 1, telomérica
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| Identificadores | |
| Símbolo | SMN1 |
| Símbolos alt. | BCD541; GEMIN1; SMA; SMA1; SMA2; SMA3; SMA4; SMA@; SMN; SMNT; T-BCD541; TDRD16A |
| Entrez | 6606 |
| OMIM | |
| RefSeq | NP_000335 |
| UniProt | Q16637 |
| Outros datos | |
| Locus | Cr. 5 :(69.35 – 69.37 Mb) |
A proteína supervivencia de motoneurona 1 tamén chamada compoñente de gems 1 ou GEMIN-1 é unha proteína que nos humanos está codificada no xene SMN1 do cromosoma 5.[1] Existen dúas variantes de transcrición deste xene.[2]
Xene
[editar | editar a fonte]Este xene é parte dunha duplicación invertida de 500 kb do cromosoma 5q13. Esta rexión duplicada contén polo menos catro xenes e elementos repetitivos, que a fan proclive a sufrir rearranxos e delecións. A repetitividade e complexidade da secuencia fixo difícil determinar a organización desta rexión xenómica. As copias teloméricas (SMN1) e centroméricas (SMN2) deste xene son case idénticas e codifican a mesma proteína.[2] (Nótese que non están no centrómero e no telómero, senón na metade en dirección ao telómero e na metade en dirección ao centrómero de dita rexión cromosómica).
Importancia clínica
[editar | editar a fonte]As mutacións na copia telomérica deste xene están asociadas coa atrofia muscular espiñal, pero as mutacións na copia centromérica (SMN2) non orixinan a doenza. A copia centromérica pode ser un modificador da doenza causada por mutación na copia telomérica. A secuencia crítica que diferencia estes dous xenes é un só nucleótido situado no exón 7 que se cre que é un amplificador de splicing do exón. Crese que estes eventos de conversión xénica poden implicar a ambos os xenes, o que orixina que varíe o número de copias de cada xene.[2]
Función
[editar | editar a fonte]A proteína codificada por este xene conténs dominios de unión a GEMIN-2, Tudor e YG-Box.[3] Localízase tanto no citoplasma coma no núcleo. No núcleo, a proteína localízase nos corpos subcelulares chamados GEMS que se encontran preto dos corpos enrolados ou de Cajal, que conteñen altas concentracións de ribonucleoproteínas pequenas nucleares (snRNPs). Esta proteína forma complexos heteroméricos con proteínas como SIP1 e GEMIN4, e tamén interacciona con varias proteínas que se sabe que están implicadas na bioxénese de snRNPs, como a proteína hnRNP U e a proteína de unión ao ARN nucleolar pequeno.[2]
Interaccións
[editar | editar a fonte]SMN1 presenta interaccións con:
- Bcl-2,[4]
- Coilina,[5][6]
- DDX20,[7][8][9][10]
- DHX9,[11]
- FBL,[12]
- FUBP1,[13]
- GAR1,[12]
- GEMIN2,[7][8][14]
- GEMIN4,[7][8]
- GEMIN5,[15]
- GEMIN7,[16][17]
- HNRNPR,[18][19]
- KPNB1,[20]
- P53,[21]
- SNRPD1,[8][14][22] e
- SNRPD2.[8]
Notas
[editar | editar a fonte]- ↑ Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M; et al. (February 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 2,3 "Entrez Gene: SMN1 survival of motor neuron 1, telomeric".
- ↑ Martin R., Gupta K, Ninan N S, Perry K, Van Duyne G D (August 2012). "The survival motor neuron protein forms soluble glycine zipper oligomers". Structure 20 (11): 1929–39. PMC 3519385. PMID 23022347. doi:10.1016/j.str.2012.08.024.
- ↑ Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (November 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature 390 (6658): 413–7. PMID 9389483. doi:10.1038/37144.
- ↑ Hebert MD, Shpargel Karl B, Ospina Jason K, Tucker Karen E, Matera A Gregory (September 2002). "Coilin methylation regulates nuclear body formation". Dev. Cell 3 (3): 329–37. PMID 12361597. doi:10.1016/S1534-5807(02)00222-8.
- ↑ Hebert MD, Szymczyk P W, Shpargel K B, Matera A G (October 2001). "Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein". Genes Dev. 15 (20): 2720–9. PMC 312817. PMID 11641277. doi:10.1101/gad.908401.
- ↑ 7,0 7,1 7,2 Carnegie GK, Sleeman Judith E, Morrice Nick, Hastie C James, Peggie Mark W, Philp Amanda, Lamond Angus I, Cohen Patricia T W (May 2003). "Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs". J. Cell. Sci. 116 (Pt 10): 1905–13. PMID 12668731. doi:10.1242/jcs.00409.
- ↑ 8,0 8,1 8,2 8,3 8,4 Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U (August 2000). "Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins". Hum. Mol. Genet. 9 (13): 1977–86. PMID 10942426. doi:10.1093/hmg/9.13.1977.
- ↑ Mourelatos Z, Dostie Josée, Paushkin Sergey, Sharma Anup, Charroux Bernard, Abel Linda, Rappsilber Juri, Mann Matthias, Dreyfuss Gideon (March 2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes Dev. 16 (6): 720–8. PMC 155365. PMID 11914277. doi:10.1101/gad.974702.
- ↑ Charroux B, Pellizzoni L, Perkinson R A, Shevchenko A, Mann M, Dreyfuss G (Dec 1999). "Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems". J. Cell Biol. 147 (6): 1181–94. PMC 2168095. PMID 10601333. doi:10.1083/jcb.147.6.1181.
- ↑ Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G (January 2001). "A functional interaction between the survival motor neuron complex and RNA polymerase II". J. Cell Biol. 152 (1): 75–85. PMC 2193649. PMID 11149922. doi:10.1083/jcb.152.1.75.
- ↑ 12,0 12,1 Pellizzoni L, Baccon J, Charroux B, Dreyfuss G (July 2001). "The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1". Curr. Biol. 11 (14): 1079–88. PMID 11509230. doi:10.1016/S0960-9822(01)00316-5.
- ↑ Williams BY, Hamilton S L, Sarkar H K (March 2000). "The survival motor neuron protein interacts with the transactivator FUSE binding protein from human fetal brain". FEBS Lett. 470 (2): 207–10. PMID 10734235. doi:10.1016/S0014-5793(00)01320-X.
- ↑ 14,0 14,1 Liu Q, Fischer U, Wang F, Dreyfuss G (September 1997). "The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins". Cell 90 (6): 1013–21. PMID 9323129. doi:10.1016/S0092-8674(00)80367-0.
- ↑ Gubitz AK, Mourelatos Zissimos, Abel Linda, Rappsilber Juri, Mann Matthias, Dreyfuss Gideon (February 2002). "Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins". J. Biol. Chem. 277 (7): 5631–6. PMID 11714716. doi:10.1074/jbc.M109448200.
- ↑ Baccon J, Pellizzoni Livio, Rappsilber Juri, Mann Matthias, Dreyfuss Gideon (August 2002). "Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex". J. Biol. Chem. 277 (35): 31957–62. PMID 12065586. doi:10.1074/jbc.M203478200.
- ↑ Pellizzoni L, Baccon Jennifer, Rappsilber Juri, Mann Matthias, Dreyfuss Gideon (March 2002). "Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component". J. Biol. Chem. 277 (9): 7540–5. PMID 11748230. doi:10.1074/jbc.M110141200.
- ↑ Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G (October 2001). "SMN interacts with a novel family of hnRNP and spliceosomal proteins". EMBO J. 20 (19): 5443–52. PMC 125643. PMID 11574476. doi:10.1093/emboj/20.19.5443.
- ↑ Rossoll W, Kröning Ann-Kathrin, Ohndorf Uta-Maria, Steegborn Clemens, Jablonka Sibylle, Sendtner Michael (January 2002). "Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons?". Hum. Mol. Genet. 11 (1): 93–105. PMID 11773003. doi:10.1093/hmg/11.1.93.
- ↑ Narayanan U, Ospina Jason K, Frey Mark R, Hebert Michael D, Matera A Gregory (July 2002). "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta". Hum. Mol. Genet. 11 (15): 1785–95. PMC 1630493. PMID 12095920. doi:10.1093/hmg/11.15.1785.
- ↑ Young PJ, Day Patricia M, Zhou Jianhua, Androphy Elliot J, Morris Glenn E, Lorson Christian L (January 2002). "A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy". J. Biol. Chem. 277 (4): 2852–9. PMID 11704667. doi:10.1074/jbc.M108769200.
- ↑ Friesen WJ, Dreyfuss G (August 2000). "Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN)". J. Biol. Chem. 275 (34): 26370–5. PMID 10851237. doi:10.1074/jbc.M003299200.
Véxase tamén
[editar | editar a fonte]Bibliografía
[editar | editar a fonte]- Hausmanowa-Petrusewicz I, Jedrzejowska M (2002). "Spinal muscular atrophy of childhood at the edge of the centuries.". Funct. Neurol. 16 (4 Suppl): 247–53. PMID 11996521.
- 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.
- van der Steege G, Draaijers TG, Grootscholten PM; et al. (1995). "A provisional transcript map of the spinal muscular atrophy (SMA) critical region.". Eur. J. Hum. Genet. 3 (2): 87–95. PMID 7552146.
- Bussaglia E, Clermont O, Tizzano E; et al. (1995). "A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients.". Nat. Genet. 11 (3): 335–7. PMID 7581461. doi:10.1038/ng1195-335.
- Gennarelli M, Lucarelli M, Capon F; et al. (1995). "Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients.". Biochem. Biophys. Res. Commun. 213 (1): 342–8. PMID 7639755. doi:10.1006/bbrc.1995.2135.
- Liu Q, Dreyfuss G (1996). "A novel nuclear structure containing the survival of motor neurons protein.". EMBO J. 15 (14): 3555–65. PMC 451956. PMID 8670859.
- van der Steege G, Grootscholten PM, Cobben JM; et al. (1996). "Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5.". Am. J. Hum. Genet. 59 (4): 834–8. PMC 1914786. PMID 8808598.
- Bürglen L, Lefebvre S, Clermont O; et al. (1997). "Structure and organization of the human survival motor neurone (SMN) gene.". Genomics 32 (3): 479–82. PMID 8838816. doi:10.1006/geno.1996.0147.
- Parsons DW, McAndrew PE, Monani UR; et al. (1997). "An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene.". Hum. Mol. Genet. 5 (11): 1727–32. PMID 8922999. doi:10.1093/hmg/5.11.1727.
- Talbot K, Ponting CP, Theodosiou AM; et al. (1997). "Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?". Hum. Mol. Genet. 6 (3): 497–500. PMID 9147655. doi:10.1093/hmg/6.3.497.
- Hahnen E, Schönling J, Rudnik-Schöneborn S; et al. (1997). "Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA).". Hum. Mol. Genet. 6 (5): 821–5. PMID 9158159. doi:10.1093/hmg/6.5.821.
- Coovert DD, Le TT, McAndrew PE; et al. (1997). "The survival motor neuron protein in spinal muscular atrophy.". Hum. Mol. Genet. 6 (8): 1205–14. PMID 9259265. doi:10.1093/hmg/6.8.1205.
- Battaglia G, Princivalle A, Forti F; et al. (1998). "Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system.". Hum. Mol. Genet. 6 (11): 1961–71. PMID 9302277. doi:10.1093/hmg/6.11.1961.
- Liu Q, Fischer U, Wang F, Dreyfuss G (1997). "The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins.". Cell 90 (6): 1013–21. PMID 9323129. doi:10.1016/S0092-8674(00)80367-0.
- Iwahashi H, Eguchi Y, Yasuhara N; et al. (1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy.". Nature 390 (6658): 413–7. PMID 9389483. doi:10.1038/37144.
- Chen Q, Baird SD, Mahadevan M; et al. (1998). "Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP.". Genomics 48 (1): 121–7. PMID 9503025. doi:10.1006/geno.1997.5141.
- Francis JW, Sandrock AW, Bhide PG; et al. (1998). "Heterogeneity of subcellular localization and electrophoretic mobility of survival motor neuron (SMN) protein in mammalian neural cells and tissues.". Proc. Natl. Acad. Sci. U.S.A. 95 (11): 6492–7. PMC 27826. PMID 9600994. doi:10.1073/pnas.95.11.6492.
- Gambardella A, Mazzei R, Toscano A; et al. (1998). "Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene.". Ann. Neurol. 44 (5): 836–9. PMID 9818944. doi:10.1002/ana.410440522.
- Parsons DW, McAndrew PE, Iannaccone ST; et al. (1999). "Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number.". Am. J. Hum. Genet. 63 (6): 1712–23. PMC 1377643. PMID 9837824. doi:10.1086/302160.
