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FLASH GENE
Symbol SMN2 contributors: shn/pgu - updated : 31-08-2016
HGNC name survival of motor neuron 2, centromeric
HGNC id 11118
EXPRESSION
Type ubiquitous
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthtongue  highly
 stomach   highly
Lymphoid/Immunethymus   highly
Reproductivefemale systemuteruscervix highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a proline-rich motif at the C terminus
  • Tudor domain
  • HOMOLOGY
    interspecies ortholog to SMN2, Pan troglodytes
    Homologene
    FAMILY
  • SMN family
  • CATEGORY motor/contractile , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,coiled bodies (Cajal)
    text localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs)
    basic FUNCTION
  • important roles in RNA metabolism
  • may be a modifier of disease caused by mutation in the telomeric copy
  • expresses only limited amounts of full-length transcript due to skipping of exon 7 caused by disruption of an SF2/ASF binding ESE (exonic splicing enhancer)
  • truncated protein that lacks exon 7, unstable and quickly degraded, however maintains the ability to rescue viability but cannot overcome neurological defects
  • CELLULAR PROCESS nucleotide, RNA splicing
    PHYSIOLOGICAL PROCESS
    text
  • SMN2 is not fully functional compared with normal SMN1 protein, including a diminished oligomerization and binding to protein substrates such as the snRNP Sm proteins
  • degraded by the proteasome
  • PATHWAY
    metabolism
    signaling
    a component
  • heteromeric complexes with proteins such as SIP1 and GEMIN4
  • forming sub-complexes with gemin proteins, complexes that localise to both stationary and dynamic neurite granules
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HDAC1 and HDAC2
  • SMN1
  • SYNCRIP
  • GAR1
  • binding KHDRBS1, through its UUUUA consensus site in SMN2 exon-7 (binding of KHDRBS1 to the UUUUA consensus in the SMN2 exon-7 is required for efficient skipping)
  • interacting with HNRNPA1 (HNRNPA1 can inhibit splicing of SMN2 exon 7 by direct binding to the 3prime ss sequence)
  • HNRNPM promotes exon 7 inclusion of SMN1 and SMN2 pre-mRNA through targeting an enhancer on exon 7 through recruiting U2AF2
  • cell & other
    REGULATION
    induced by inhibition of an individual HDAC which is sufficient to increase SMN2 transcription as well as promote the inclusion of exon 7
    Other transcriptional regulation during cellular differentiation and development
    modulated expression of SMN2 by histone acetylation (through HDAC2 or HDAC1)
    ASSOCIATED DISORDERS
    corresponding disease(s) AMCSMA1 , SMA , SMA2 , SMA3 , SMA4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in one case with spinal muscular atrophy, without any detectable lesion of SMN1
    constitutional   deletion    
    homozygously deleted in sporadic SLA with shorter time of survival
    Susceptibility
  • to spinal muscular amyotrophy
  • splicing defect in SMN2 causes SMN deficiency because it fortuitously creates a degron resulting in major perturbations in RNA metabolism
  • Variant & Polymorphism
    Candidate gene
  • an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but probably not the only one
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularspinal muscular atrophy 
    in SMN-deficient mice expression of an increasing copy number of SMN2 cDNA transgenes proportionately lessens SMA severity
    neuromuscularspinal muscular atrophy 
    inhibition of SMN2 gene silencing conferred by DNA methylation might represent a promising strategy for pharmacologic SMA therapy
    neuromuscularspinal muscular atrophy 
    potential therapeutic benefit in increasing the SMN2 gene expression in order to decrease the severity of the SMA
    neuromuscularspinal muscular atrophy 
    use of single-stranded oligonucleotides to direct genetic conversion of SMN2 to SMN1 in human cells from SMA patients
    neuromuscularspinal muscular atrophy 
    inhibition of KHDRBS1 activity, through competition with dominant-negative mutants, provides a valuable approach for the rescue of SMN activity
    ANIMAL & CELL MODELS