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Survival motor neuron protein
Tudor domain from human SMN. PDB 1g5v [1]
Identifiers
SymbolSMN
Pfam PF06003
Pfam clan CL0049
InterPro IPR010304
SCOP2 1mhn / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Survival of motor neuron or survival motor neuron (SMN) is a protein that in humans is encoded by the SMN1 and SMN2 genes.

SMN is found in the cytoplasm of all animal cells and also in the nuclear gems. It functions in transcriptional regulation, telomerase regeneration and cellular trafficking. [2] SMN deficiency, primarily due to mutations in SMN1, results in widespread splicing defects, especially in spinal motor neurons, and is one cause of spinal muscular atrophy. Research also showed a possible role of SMN in neuronal migration and/or differentiation. [3]

Function

The SMN protein contains GEMIN2-binding, Tudor and YG-Box domains. [4] 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 GEMIN2 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. [5]

SMN complex

SMN complex refers to the entire multi-protein complex involved in the assembly of snRNPs, the essential components of spliceosomal machinery. [6] The complex, apart from the "proper" survival of motor neuron protein, includes at least six other proteins ( gem-associated protein 2, 3, 4, 5, 6 and 7. [6]

Interactions

SMN has been shown to interact with:

Evolutionary conservation

SMN is evolutionarily conserved including the Fungi kingdom, though only fungal organisms with a great number of introns have the Smn gene (or the splicing factor spf30 paralogue). Surprisingly, these are filamentous fungus which have mycelia, so suggesting analogy to the neuronal axons. [25]

See also

References

  1. ^ Selenko P, Sprangers R, Stier G, Bühler D, Fischer U, Sattler M (January 2001). "SMN tudor domain structure and its interaction with the Sm proteins". Nature Structural Biology. 8 (1): 27–31. doi: 10.1038/83014. PMID  11135666.
  2. ^ Singh NN, Shishimorova M, Cao LC, Gangwani L, Singh RN (2009). "A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy". RNA Biology. 6 (3): 341–50. doi: 10.4161/rna.6.3.8723. PMC  2734876. PMID  19430205.
  3. ^ Giavazzi A, Setola V, Simonati A, Battaglia G (March 2006). "Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system". Journal of Neuropathology and Experimental Neurology. 65 (3): 267–77. doi: 10.1097/01.jnen.0000205144.54457.a3. PMID  16651888.
  4. ^ 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.
  5. ^ "Entrez Gene: SMN1 survival of motor neuron 1, telomeric".
  6. ^ a b Gubitz AK, Feng W, Dreyfuss G (May 2004). "The SMN complex". Experimental Cell Research. 296 (1): 51–6. doi: 10.1016/j.yexcr.2004.03.022. PMID  15120993.
  7. ^ 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. Bibcode: 1997Natur.390..413I. doi: 10.1038/37144. PMID  9389483.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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. Bibcode: 2001CBio...11.1079P. doi: 10.1016/S0960-9822(01)00316-5. PMID  11509230.
  15. ^ 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. Bibcode: 2000FEBSL.470..207W. doi: 10.1016/S0014-5793(00)01320-X. PMID  10734235.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ Mier P, Pérez-Pulido AJ (January 2012). "Fungal Smn and Spf30 homologues are mainly present in filamentous fungi and genomes with many introns: implications for spinal muscular atrophy". Gene. 491 (2): 135–41. doi: 10.1016/j.gene.2011.10.006. PMID  22020225.

External links

Retrieved from " https://en.wikipedia.org/?title=Survival_of_motor_neuron&oldid=1228193980"
From Wikipedia, the free encyclopedia
Survival motor neuron protein
Tudor domain from human SMN. PDB 1g5v [1]
Identifiers
SymbolSMN
Pfam PF06003
Pfam clan CL0049
InterPro IPR010304
SCOP2 1mhn / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Survival of motor neuron or survival motor neuron (SMN) is a protein that in humans is encoded by the SMN1 and SMN2 genes.

SMN is found in the cytoplasm of all animal cells and also in the nuclear gems. It functions in transcriptional regulation, telomerase regeneration and cellular trafficking. [2] SMN deficiency, primarily due to mutations in SMN1, results in widespread splicing defects, especially in spinal motor neurons, and is one cause of spinal muscular atrophy. Research also showed a possible role of SMN in neuronal migration and/or differentiation. [3]

Function

The SMN protein contains GEMIN2-binding, Tudor and YG-Box domains. [4] 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 GEMIN2 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. [5]

SMN complex

SMN complex refers to the entire multi-protein complex involved in the assembly of snRNPs, the essential components of spliceosomal machinery. [6] The complex, apart from the "proper" survival of motor neuron protein, includes at least six other proteins ( gem-associated protein 2, 3, 4, 5, 6 and 7. [6]

Interactions

SMN has been shown to interact with:

Evolutionary conservation

SMN is evolutionarily conserved including the Fungi kingdom, though only fungal organisms with a great number of introns have the Smn gene (or the splicing factor spf30 paralogue). Surprisingly, these are filamentous fungus which have mycelia, so suggesting analogy to the neuronal axons. [25]

See also

References

  1. ^ Selenko P, Sprangers R, Stier G, Bühler D, Fischer U, Sattler M (January 2001). "SMN tudor domain structure and its interaction with the Sm proteins". Nature Structural Biology. 8 (1): 27–31. doi: 10.1038/83014. PMID  11135666.
  2. ^ Singh NN, Shishimorova M, Cao LC, Gangwani L, Singh RN (2009). "A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy". RNA Biology. 6 (3): 341–50. doi: 10.4161/rna.6.3.8723. PMC  2734876. PMID  19430205.
  3. ^ Giavazzi A, Setola V, Simonati A, Battaglia G (March 2006). "Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system". Journal of Neuropathology and Experimental Neurology. 65 (3): 267–77. doi: 10.1097/01.jnen.0000205144.54457.a3. PMID  16651888.
  4. ^ 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.
  5. ^ "Entrez Gene: SMN1 survival of motor neuron 1, telomeric".
  6. ^ a b Gubitz AK, Feng W, Dreyfuss G (May 2004). "The SMN complex". Experimental Cell Research. 296 (1): 51–6. doi: 10.1016/j.yexcr.2004.03.022. PMID  15120993.
  7. ^ 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. Bibcode: 1997Natur.390..413I. doi: 10.1038/37144. PMID  9389483.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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. Bibcode: 2001CBio...11.1079P. doi: 10.1016/S0960-9822(01)00316-5. PMID  11509230.
  15. ^ 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. Bibcode: 2000FEBSL.470..207W. doi: 10.1016/S0014-5793(00)01320-X. PMID  10734235.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ Mier P, Pérez-Pulido AJ (January 2012). "Fungal Smn and Spf30 homologues are mainly present in filamentous fungi and genomes with many introns: implications for spinal muscular atrophy". Gene. 491 (2): 135–41. doi: 10.1016/j.gene.2011.10.006. PMID  22020225.

External links

Retrieved from " https://en.wikipedia.org/?title=Survival_of_motor_neuron&oldid=1228193980"

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