SMN1

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survival of motor neuron 1, telomeric
Protein SMN1 PDB 1g5v.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases SMN1, BCD541, GEMIN1, SMA, SMA1, SMA2, SMA3, SMA4, SMA@, SMN, SMNT, T-BCD541, TDRD16A
External IDs HomoloGene: 292 GeneCards: 6606
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000344
NM_001297715
NM_022874

n/a

RefSeq (protein)

n/a

Location (UCSC) Chr 5: 70.05 – 70.08 Mb n/a
PubMed search [1] n/a
Wikidata
View/Edit Human

Survival of motor neuron 1 (SMN1), also known as component of gems 1 or GEMIN1, is a gene that encodes the SMN protein in humans.[1][2]

Gene[edit]

SMN1 is the telomeric copy of the gene encoding the SMN protein; the centromeric copy is termed SMN2. SMN1 and SMN2 are part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. SMN1 and SMN2 are nearly identical and encode the same protein.[2] The critical sequence difference between the two is a single nucleotide in exon 7 which is thought to be an exon splice enhancer. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene.[2]

Clinical significance[edit]

Mutations in SMN1 are associated with spinal muscular atrophy. Mutations in SMN2 alone do not lead to disease, although mutations in both SMN1 and SMN2 result in embryonic death.

Function[edit]

Survival of motor neuron (SMN), the protein encoded by this gene, contains GEMIN2-binding, Tudor and YG-Box domains.[3] It localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as SIP1 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein.[2]

Interactions[edit]

SMN1 has been shown to interact with:

References[edit]

  1. ^ 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. doi:10.1016/0092-8674(95)90460-3. PMID 7813012. 
  2. ^ a b c d "Entrez Gene: SMN1 survival of motor neuron 1, telomeric". 
  3. ^ Martin R, Gupta K, Ninan NS, Perry K, Van Duyne GD (November 2012). "The survival motor neuron protein forms soluble glycine zipper oligomers". Structure 20 (11): 1929–39. doi:10.1016/j.str.2012.08.024. PMC 3519385. PMID 23022347. 
  4. ^ 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. doi:10.1038/37144. PMID 9389483. 
  5. ^ Hebert MD, Shpargel KB, Ospina JK, Tucker KE, Matera AG (September 2002). "Coilin methylation regulates nuclear body formation". Developmental Cell 3 (3): 329–37. doi:10.1016/S1534-5807(02)00222-8. PMID 12361597. 
  6. ^ Hebert MD, Szymczyk PW, Shpargel KB, Matera AG (October 2001). "Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein". Genes & Development 15 (20): 2720–9. doi:10.1101/gad.908401. PMC 312817. PMID 11641277. 
  7. ^ a b c Carnegie GK, Sleeman JE, Morrice N, Hastie CJ, Peggie MW, Philp A, Lamond AI, Cohen PT (May 2003). "Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs". Journal of Cell Science 116 (Pt 10): 1905–13. doi:10.1242/jcs.00409. PMID 12668731. 
  8. ^ a b c d e 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". Human Molecular Genetics 9 (13): 1977–86. doi:10.1093/hmg/9.13.1977. PMID 10942426. 
  9. ^ Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G (March 2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes & Development 16 (6): 720–8. doi:10.1101/gad.974702. PMC 155365. PMID 11914277. 
  10. ^ Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G (December 1999). "Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems". The Journal of Cell Biology 147 (6): 1181–94. doi:10.1083/jcb.147.6.1181. PMC 2168095. PMID 10601333. 
  11. ^ 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". The Journal of Cell Biology 152 (1): 75–85. doi:10.1083/jcb.152.1.75. PMC 2193649. PMID 11149922. 
  12. ^ a b 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". Current Biology 11 (14): 1079–88. doi:10.1016/S0960-9822(01)00316-5. PMID 11509230. 
  13. ^ Williams BY, Hamilton SL, Sarkar HK (March 2000). "The survival motor neuron protein interacts with the transactivator FUSE binding protein from human fetal brain". FEBS Letters 470 (2): 207–10. doi:10.1016/S0014-5793(00)01320-X. PMID 10734235. 
  14. ^ a b 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. doi:10.1016/S0092-8674(00)80367-0. PMID 9323129. 
  15. ^ Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G (February 2002). "Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins". The Journal of Biological Chemistry 277 (7): 5631–6. doi:10.1074/jbc.M109448200. PMID 11714716. 
  16. ^ Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G (August 2002). "Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex". The Journal of Biological Chemistry 277 (35): 31957–62. doi:10.1074/jbc.M203478200. PMID 12065586. 
  17. ^ Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G (March 2002). "Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component". The Journal of Biological Chemistry 277 (9): 7540–5. doi:10.1074/jbc.M110141200. PMID 11748230. 
  18. ^ Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G (October 2001). "SMN interacts with a novel family of hnRNP and spliceosomal proteins". The EMBO Journal 20 (19): 5443–52. doi:10.1093/emboj/20.19.5443. PMC 125643. PMID 11574476. 
  19. ^ Rossoll W, Kröning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M (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?". Human Molecular Genetics 11 (1): 93–105. doi:10.1093/hmg/11.1.93. PMID 11773003. 
  20. ^ Narayanan U, Ospina JK, Frey MR, Hebert MD, Matera AG (July 2002). "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta". Human Molecular Genetics 11 (15): 1785–95. doi:10.1093/hmg/11.15.1785. PMC 1630493. PMID 12095920. 
  21. ^ Young PJ, Day PM, Zhou J, Androphy EJ, Morris GE, Lorson CL (January 2002). "A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy". The Journal of Biological Chemistry 277 (4): 2852–9. doi:10.1074/jbc.M108769200. PMID 11704667. 
  22. ^ 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)". The Journal of Biological Chemistry 275 (34): 26370–5. doi:10.1074/jbc.M003299200. PMID 10851237. 

Further reading[edit]

  • Hausmanowa-Petrusewicz I, Jedrzejowska M (2002). "Spinal muscular atrophy of childhood at the edge of the centuries". Functional Neurology 16 (4 Suppl): 247–53. PMID 11996521. 
  • Paushkin S, Gubitz AK, Massenet S, Dreyfuss G (June 2002). "The SMN complex, an assemblyosome of ribonucleoproteins". Current Opinion in Cell Biology 14 (3): 305–12. doi:10.1016/S0955-0674(02)00332-0. PMID 12067652. 
  • van der Steege G, Draaijers TG, Grootscholten PM, Osinga J, Anzevino R, Velonà I, Den Dunnen JT, Scheffer H, Brahe C, van Ommen GJ (1995). "A provisional transcript map of the spinal muscular atrophy (SMA) critical region". European Journal of Human Genetics 3 (2): 87–95. PMID 7552146. 
  • Bussaglia E, Clermont O, Tizzano E, Lefebvre S, Bürglen L, Cruaud C, Urtizberea JA, Colomer J, Munnich A, Baiget M (November 1995). "A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients". Nature Genetics 11 (3): 335–7. doi:10.1038/ng1195-335. PMID 7581461. 
  • Gennarelli M, Lucarelli M, Capon F, Pizzuti A, Merlini L, Angelini C, Novelli G, Dallapiccola B (August 1995). "Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients". Biochemical and Biophysical Research Communications 213 (1): 342–8. doi:10.1006/bbrc.1995.2135. PMID 7639755. 
  • Liu Q, Dreyfuss G (July 1996). "A novel nuclear structure containing the survival of motor neurons protein". The EMBO Journal 15 (14): 3555–65. PMC 451956. PMID 8670859. 
  • van der Steege G, Grootscholten PM, Cobben JM, Zappata S, Scheffer H, den Dunnen JT, van Ommen GJ, Brahe C, Buys CH (October 1996). "Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5". American Journal of Human Genetics 59 (4): 834–8. PMC 1914786. PMID 8808598. 
  • Bürglen L, Lefebvre S, Clermont O, Burlet P, Viollet L, Cruaud C, Munnich A, Melki J (March 1996). "Structure and organization of the human survival motor neurone (SMN) gene". Genomics 32 (3): 479–82. doi:10.1006/geno.1996.0147. PMID 8838816. 
  • Parsons DW, McAndrew PE, Monani UR, Mendell JR, Burghes AH, Prior TW (November 1996). "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". Human Molecular Genetics 5 (11): 1727–32. doi:10.1093/hmg/5.11.1727. PMID 8922999. 
  • Talbot K, Ponting CP, Theodosiou AM, Rodrigues NR, Surtees R, Mountford R, Davies KE (March 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?". Human Molecular Genetics 6 (3): 497–500. doi:10.1093/hmg/6.3.497. PMID 9147655. 
  • Hahnen E, Schönling J, Rudnik-Schöneborn S, Raschke H, Zerres K, Wirth B (May 1997). "Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA)". Human Molecular Genetics 6 (5): 821–5. doi:10.1093/hmg/6.5.821. PMID 9158159. 
  • Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AH (August 1997). "The survival motor neuron protein in spinal muscular atrophy". Human Molecular Genetics 6 (8): 1205–14. doi:10.1093/hmg/6.8.1205. PMID 9259265. 
  • Battaglia G, Princivalle A, Forti F, Lizier C, Zeviani M (October 1997). "Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system". Human Molecular Genetics 6 (11): 1961–71. doi:10.1093/hmg/6.11.1961. PMID 9302277. 
  • 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. doi:10.1016/S0092-8674(00)80367-0. PMID 9323129. 
  • 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. doi:10.1038/37144. PMID 9389483. 
  • Chen Q, Baird SD, Mahadevan M, Besner-Johnston A, Farahani R, Xuan J, Kang X, Lefebvre C, Ikeda JE, Korneluk RG, MacKenzie AE (February 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. doi:10.1006/geno.1997.5141. PMID 9503025. 
  • Francis JW, Sandrock AW, Bhide PG, Vonsattel JP, Brown RH (May 1998). "Heterogeneity of subcellular localization and electrophoretic mobility of survival motor neuron (SMN) protein in mammalian neural cells and tissues". Proceedings of the National Academy of Sciences of the United States of America 95 (11): 6492–7. doi:10.1073/pnas.95.11.6492. PMC 27826. PMID 9600994. 
  • Gambardella A, Mazzei R, Toscano A, Annesi G, Pasqua A, Annesi F, Quattrone F, Oliveri RL, Valentino P, Bono F, Aguglia U, Zappia M, Vita G, Quattrone A (November 1998). "Spinal muscular atrophy due to an isolated deletion of exon 8 of the telomeric survival motor neuron gene". Annals of Neurology 44 (5): 836–9. doi:10.1002/ana.410440522. PMID 9818944. 
  • Parsons DW, McAndrew PE, Iannaccone ST, Mendell JR, Burghes AH, Prior TW (December 1998). "Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number". American Journal of Human Genetics 63 (6): 1712–23. doi:10.1086/302160. PMC 1377643. PMID 9837824. 

External links[edit]

  • Prior TW, Russman BS (2013). Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Fong CT, Mefford HC, Smith RJ, Stephens K, eds. "Spinal Muscular Atrophy". GeneReviews [Internet]. PMID 20301526. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.