survival of motor neuron 1 protein

Summary

Summary: An SMN complex protein that contains a TUDOR DOMAIN and is essential for the function of the SMN protein complex. In humans, the protein is encoded by a single gene found near the inversion TELOMERE of a large inverted region of CHROMOSOME 5. Mutations in the gene coding for survival of motor neuron 1 protein may result in SPINAL MUSCULAR ATROPHIES OF CHILDHOOD.

Top Publications

  1. . [SMN1 Gene Point Mutations in Type I-IV Proximal Spinal Muscular Atrophy Patients with a Single Copy of SMN1]. Genetika. 2015;51:1075-82 pubmed
    ..Only one mutation, c.43C > T (p.Gln15X), emerged de novo in a genital cell of the child's father. ..
  2. Tejero R, Lopez Manzaneda M, Arumugam S, Tabares L. Synaptotagmin-2, and -1, linked to neurotransmission impairment and vulnerability in Spinal Muscular Atrophy. Hum Mol Genet. 2016;25:4703-4716 pubmed publisher
    ..Together, we propose that the strong reduction of Syt2 and SV2B are key factors of the functional synaptic alteration and that the physiological downregulation of Syt1 plays a determinant role in muscle vulnerability in SMA. ..
  3. Fletcher E, Simon C, Pagiazitis J, Chalif J, Vukojicic A, Drobac E, et al. Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy. Nat Neurosci. 2017;20:905-916 pubmed publisher
    ..Our results demonstrate a key role of excitatory synaptic drive in shaping the function of motor neurons during development and the contribution of its disruption to a neurodegenerative disease. ..
  4. Hendrickson B, Donohoe C, Akmaev V, Sugarman E, Labrousse P, Boguslavskiy L, et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 2009;46:641-4 pubmed publisher
    ..This study provides an accurate assessment of allele frequencies and estimates of adjusted genetic risk that were previously unavailable to clinicians and patients considering testing. ..
  5. Rage F, Boulisfane N, Rihan K, Neel H, Gostan T, Bertrand E, et al. Genome-wide identification of mRNAs associated with the protein SMN whose depletion decreases their axonal localization. RNA. 2013;19:1755-66 pubmed publisher
    ..Moreover, they localize in cell processes in an SMN-dependent manner. Thus, low SMN levels might result in localization deficiencies of mRNAs required for axonogenesis. ..
  6. Solov ev A, Grishchenko N, Livshits L. [Spinal muscular atrophy carrier frequency in Ukraine]. Genetika. 2013;49:1126-8 pubmed
    ..The carrier frequency for this group of Ukrainians was estimated as 3.24% (1/31). The results of our study showing the high prevalence of carriers warrant the importance of population screening for SMA in Ukraine. ..
  7. Zarkov M, Stojadinović A, Sekulić S, Barjaktarović I, Perić S, Keković G, et al. Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene. Vojnosanit Pregl. 2015;72:859-63 pubmed
    ..05). In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected. ..
  8. Kim E, Choi E. SMN1 functions as a novel inhibitor for TRAF6-mediated NF-?B signaling. Biochim Biophys Acta Mol Cell Res. 2017;1864:760-770 pubmed publisher
    ..Our results thus suggest that SMN functions as a natural inhibitor for IL-1?-induced NF-?B signaling by targeting TRAF6 and the IKK complex. ..
  9. Rihan K, Antoine E, Maurin T, Bardoni B, Bordonné R, Soret J, et al. A new cis-acting motif is required for the axonal SMN-dependent Anxa2 mRNA localization. RNA. 2017;23:899-909 pubmed publisher
    ..Altogether, our studies show that this G-motif represents a novel and essential determinant for axonal localization of the Anxa2 mRNA mediated by the SMN complex. ..

More Information

Publications18

  1. Martin J, Nguyen T, Grunseich C, Nofziger J, Lee P, Fields D, et al. Decreased Motor Neuron Support by SMA Astrocytes due to Diminished MCP1 Secretion. J Neurosci. 2017;37:5309-5318 pubmed publisher
    ..This study reveals a novel aspect of astrocyte dysfunction in SMA and indicates a possible approach for improving motor neuron growth and survival in this disease. ..
  2. Mendell J, Al Zaidy S, Shell R, Arnold W, Rodino Klapac L, Prior T, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017;377:1713-1722 pubmed publisher
    ..Further studies are necessary to confirm the safety and efficacy of this gene therapy. (Funded by AveXis and others; ClinicalTrials.gov number, NCT02122952 .). ..
  3. Paton D. Nusinersen: antisense oligonucleotide to increase SMN protein production in spinal muscular atrophy. Drugs Today (Barc). 2017;53:327-337 pubmed publisher
    ..In addition, there have been significant extensions in life expectancy. These findings led to the U.S. and European approval of nusinersen for use in SMA patients of all ages. ..
  4. Li W. How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?. PLoS ONE. 2017;12:e0178519 pubmed publisher
    ..From the computational analysis, it is also possible that SMN's Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface. ..
  5. Rietz A, Li H, Quist K, Cherry J, Lorson C, Burnett B, et al. Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy. J Med Chem. 2017;60:4594-4610 pubmed publisher
    ..This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA. ..
  6. Boyd P, Tu W, Shorrock H, Groen E, Carter R, Powis R, et al. Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy. PLoS Genet. 2017;13:e1006744 pubmed publisher
    ..We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo. ..
  7. Li L, Zhou W, Fang P, Zhong Z, Xie J, Yan T, et al. Evaluation and comparison of three assays for molecular detection of spinal muscular atrophy. Clin Chem Lab Med. 2017;55:358-367 pubmed publisher
    ..The CNVplex assay could be used to detect SMAs with complicated gene structures. The assays were reliable and could be used as alternative methods for clinical diagnosis of SMA. ..
  8. Wishart T, Mutsaers C, Riessland M, Reimer M, Hunter G, Hannam M, et al. Dysregulation of ubiquitin homeostasis and ?-catenin signaling promote spinal muscular atrophy. J Clin Invest. 2014;124:1821-34 pubmed publisher
  9. Custer S, Todd A, Singh N, Androphy E. Dilysine motifs in exon 2b of SMN protein mediate binding to the COPI vesicle protein ?-COP and neurite outgrowth in a cell culture model of spinal muscular atrophy. Hum Mol Genet. 2013;22:4043-52 pubmed publisher
    ..We conclude that the interaction between SMN and ?-COP serves an important function in the growth and maintenance of motor neuron processes and may play a significant role in the pathogenesis of SMA. ..