- 関
- 脊髄性筋萎縮症
- 294アミノ酸からなるRNA結合タンパクで、効率の良いsnRNP(小粒子核リボ蛋白複合体)の組み立てに必要である。機能欠損遺伝子のホモ接合により脊髄筋萎縮症を発症する(つまり常染色体劣性遺伝)。
参考
- 1. SURVIVAL OF MOTOR NEURON 1; SMN1
- http://omim.org/entry/600354
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/30 19:03:44」(JST)
[Wiki en表示]
| Survival of motor neuron 1, telomeric |
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PDB rendering based on 1g5v[1].
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| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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1G5V, 1MHN, 2LEH, 3S6N, 4A4E, 4A4G, 4GLI, 4NL6, 4NL7, 4QQ6
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| Identifiers |
| Symbols |
SMN1 ; BCD541; GEMIN1; SMA; SMA1; SMA2; SMA3; SMA4; SMA@; SMN; SMNT; T-BCD541; TDRD16A |
| External IDs |
OMIM: 600354 MGI: 109257 HomoloGene: 292 ChEMBL: 1293232 GeneCards: SMN1 Gene |
| Gene ontology |
| Molecular function |
• RNA binding
• protein binding
• identical protein binding
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| Cellular component |
• nucleus
• nucleoplasm
• spliceosomal complex
• cytoplasm
• cytosol
• Cajal body
• Z disc
• SMN complex
• SMN-Sm protein complex
• Gemini of coiled bodies
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| Biological process |
• spliceosomal complex assembly
• spliceosomal snRNP assembly
• nervous system development
• gene expression
• ncRNA metabolic process
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| Sources: Amigo / QuickGO |
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| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
6606 |
20595 |
| Ensembl |
ENSG00000172062 |
ENSMUSG00000021645 |
| UniProt |
Q16637 |
P97801 |
| RefSeq (mRNA) |
NM_000344 |
NM_001252629 |
| RefSeq (protein) |
NP_000335 |
NP_001239558 |
| Location (UCSC) |
Chr 5:
70.05 – 70.08 Mb |
Chr 13:
100.12 – 100.14 Mb |
| PubMed search |
[1] |
[2] |
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Survival motor neuron protein also known as component of gems 1 or gemin-1 is a protein that in humans is encoded by the SMN1 gene.[2] Two transcript variants are produced by this gene.[3]
Contents
- 1 Gene
- 2 Clinical significance
- 3 Function
- 4 Interactions
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Gene
This gene is 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. The telomeric and centromeric copies of this gene are nearly identical and encode the same protein.[3]
Clinical significance
Mutations in the telomeric copy of this gene are associated with spinal muscular atrophy; mutations in the centromeric copy do not lead to disease. The centromeric copy may be a modifier of disease caused by mutation in the telomeric copy. The critical sequence difference between the two genes 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.[3]
Function
The protein encoded by this gene 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 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.[3]
Interactions
SMN1 has been shown to interact with:
- Bcl-2,[5]
- Coilin,[6][7]
- DDX20,[8][9][10][11]
- DHX9,[12]
- FBL,[13]
- FUBP1,[14]
- GAR1,[13]
- GEMIN2,[8][9][15]
- GEMIN4,[8][9]
- GEMIN5,[16]
- GEMIN7,[17][18]
- HNRNPR,[19][20]
- KPNB1,[21]
- P53,[22]
- SNRPD1,[9][15][23] and
- SNRPD2.[9]
See also
- SMN2
- Spinal muscular atrophy
- Survival of motor neuron
References
- ^ Sattler, M.; Selenko, P.; Sprangers, R.; Stier, G.; Bühler, D.; Fischer, U. (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. edit
- ^ 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. doi:10.1016/0092-8674(95)90460-3. PMID 7813012.
- ^ a b c d "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. doi:10.1016/j.str.2012.08.024. PMC 3519385. PMID 23022347.
- ^ 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.
- ^ 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. doi:10.1016/S1534-5807(02)00222-8. PMID 12361597.
- ^ 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. doi:10.1101/gad.908401. PMC 312817. PMID 11641277.
- ^ a b c 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. doi:10.1242/jcs.00409. PMID 12668731.
- ^ 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". Hum. Mol. Genet. 9 (13): 1977–86. doi:10.1093/hmg/9.13.1977. PMID 10942426.
- ^ 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. doi:10.1101/gad.974702. PMC 155365. PMID 11914277.
- ^ 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. doi:10.1083/jcb.147.6.1181. PMC 2168095. PMID 10601333.
- ^ 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. doi:10.1083/jcb.152.1.75. PMC 2193649. PMID 11149922.
- ^ 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". Curr. Biol. 11 (14): 1079–88. doi:10.1016/S0960-9822(01)00316-5. PMID 11509230.
- ^ 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. doi:10.1016/S0014-5793(00)01320-X. PMID 10734235.
- ^ 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.
- ^ 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. doi:10.1074/jbc.M109448200. PMID 11714716.
- ^ 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. doi:10.1074/jbc.M203478200. PMID 12065586.
- ^ 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. doi:10.1074/jbc.M110141200. PMID 11748230.
- ^ 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. doi:10.1093/emboj/20.19.5443. PMC 125643. PMID 11574476.
- ^ 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. doi:10.1093/hmg/11.1.93. PMID 11773003.
- ^ 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. doi:10.1093/hmg/11.15.1785. PMC 1630493. PMID 12095920.
- ^ 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. doi:10.1074/jbc.M108769200. PMID 11704667.
- ^ 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. doi:10.1074/jbc.M003299200. PMID 10851237.
Further reading
- 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. doi:10.1016/S0955-0674(02)00332-0. PMID 12067652.
- 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. doi:10.1038/ng1195-335. PMID 7581461.
- 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. doi:10.1006/bbrc.1995.2135. PMID 7639755.
- 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. doi:10.1006/geno.1996.0147. PMID 8838816.
- 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. doi:10.1093/hmg/5.11.1727. PMID 8922999.
- 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. doi:10.1093/hmg/6.3.497. PMID 9147655.
- 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. doi:10.1093/hmg/6.5.821. PMID 9158159.
- 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. doi:10.1093/hmg/6.8.1205. PMID 9259265.
- 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. doi:10.1093/hmg/6.11.1961. PMID 9302277.
- 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. doi:10.1016/S0092-8674(00)80367-0. PMID 9323129.
- 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. doi:10.1038/37144. PMID 9389483.
- 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. doi:10.1006/geno.1997.5141. PMID 9503025.
- 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. doi:10.1073/pnas.95.11.6492. PMC 27826. PMID 9600994.
- 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. doi:10.1002/ana.410440522. PMID 9818944.
- 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. doi:10.1086/302160. PMC 1377643. PMID 9837824.
External links
- GeneReviews/NCBI/NIH/UW entry on Spinal Muscular Atrophy including Arthrogryposis Multiplex Congenita-Spinal Muscular Atrophy (AMC-SMA); Spinal Muscular Atrophy I (Werdnig-Hoffmann Disease, SMA1); Spinal Muscular Atrophy II (SMA II); Spinal Muscular Atrophy III (Kugelberg-Welander Disease, SMA III); Spinal Muscular Atrophy IV (SMA IV)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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PDB gallery
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1g5v: SOLUTION STRUCTURE OF THE TUDOR DOMAIN OF THE HUMAN SMN PROTEIN
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1mhn: High resolution crystal structure of the SMN Tudor domain
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UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Solving the puzzle of spinal muscular atrophy: What are the missing pieces?
- Tiziano FD, Melki J, Simard LR.SourceIstituto di Genetica Medica, Università Cattolica del Sacro Cuore, Roma, Italy.
- American journal of medical genetics. Part A.Am J Med Genet A.2013 Nov;161(11):2836-45. doi: 10.1002/ajmg.a.36251. Epub 2013 Oct 3.
- Spinal muscular atrophy (SMA) is an autosomal recessive, lower motor neuron disease. Clinical heterogeneity is pervasive: three infantile (type I-III) and one adult-onset (type IV) forms are recognized. Type I SMA is the most common genetic cause of death in infancy and accounts for about 50% of all
- PMID 24124019
- Spinal muscular atrophy: new findings for an old pathology.
- Bottai D, Adami R.SourceDepartment of Science Health, University of Milan, Milano, Italy.
- Brain pathology (Zurich, Switzerland).Brain Pathol.2013 Nov;23(6):613-22. doi: 10.1111/bpa.12071. Epub 2013 Jun 28.
- Understanding the events that are responsible for a disease is mandatory for setting up a therapeutic strategy. Although spinal muscular atrophy (SMA) is considered a rare neurodegenerative pathology, its impact in our society is really devastating as it strikes young people from birth onward, and i
- PMID 23750936
- Diabetic Ketoacidosis in an Adult Patient With Spinal Muscular Atrophy Type II: Further Evidence of Extraneural Pathology Due to Survival Motor Neuron 1 Mutation?
- Lamarca NH, Golden L, John RM, Naini A, Vivo DC, Sproule DM.Source1Columbia University Medical Center, New York, NY.
- Journal of child neurology.J Child Neurol.2013 Nov;28(11):1517-1520. Epub 2012 Oct 3.
- Spinal muscular atrophy is an autosomal recessive neurodegenerative disease caused by homozygous mutation to the survival motor neuron 1 (SMN1) gene. Historically, spinal muscular atrophy has been considered to almost exclusively affect the function and survival of alpha motor neurons of the spinal
- PMID 23034979
Japanese Journal
- A new method for SMN1 and hybrid SMN gene analysis in spinal muscular atrophy using long-range PCR followed by sequencing
- Modeling the early phenotype at the neuromuscular junction of spinal muscular atrophy using patient-derived iPSCs.
- 日本小児神経学会推薦総説 脊髄性筋萎縮症 遺伝子診断から治療戦略まで
- 日本小児科学会雑誌 = The journal of the Japan Pediatric Society 118(9), 1315-1323, 2014-09
- NAID 40020215577
Related Links
- SMN1 遺伝子とSMN2遺伝子の配列の違いはイントロン6、7、エクソン7 、8における5塩基のみである （図3）。その差を利用して、遺伝子診断で ...
- The official name of this gene is “survival of motor neuron 1, telomeric.” SMN1 is the gene's official symbol. The SMN1 gene is also known by other names, listed below. Read more about gene names and symbols on the About ...
Related Pictures
★リンクテーブル★
[★]
- 英
- spinal muscular atrophy, SMA
- 同？
- 脊髄進行性筋萎縮症 progressive spinal muscular atrophy
- 関
- 筋萎縮、運動ニューロン疾患, motor neuron disease, MND
運動ニューロン病
- BET.439
- 上位運動ニューロン and/or 下位運動ニューロンが選択的に傷害される疾患の総称
遺伝形式
原因遺伝子
症状
- 下位運動ニューロンの脱落・変性
- 近位筋優位の筋萎縮 ← 神経原性の筋萎縮なのに・・・ (cf. 筋萎縮)
参考
uptodate
- 1. [charged] 脊髄性筋萎縮症 - uptodate [1]
OMIM
- 1. SPINAL MUSCULAR ATROPHY, TYPE I; SMA1, Gene map locus 5q12.2-q13.3
- http://omim.org/entry/253300
- 2. SPINAL MUSCULAR ATROPHY, TYPE II; SMA2, Gene map locus 5q12.2-q13.3
- http://omim.org/entry/253550
- 3. SPINAL MUSCULAR ATROPHY, TYPE III; SMA3, Gene map locus 5q12.2-q13.3, 5q12.2-q13.3
- http://omim.org/entry/253400
- 4. SPINAL MUSCULAR ATROPHY, TYPE IV; SMA4, Gene map locus 5q12.2-q13.3
- http://omim.org/entry/271150
[★]