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Symbol SMN1 contributors: shn/npt/pgu - updated : 15-10-2013
HGNC name survival of motor neuron 1, telomeric
HGNC id 11117
  • GEMIN2 binding domain
  • self association domain
  • lysine rich domain (K-rich)
  • Tudor domains bound to symmetric and asymmetric dimethylated arginine (DMA) that is inherent in the RNP complexes (PMID;
  • proline-rich domain (P-rich)
  • conserved YG box
  • conjugated GlycoP
    mono polymer heteromer , oligo
    interspecies ortholog to Smn1, Rattus norvegicus
    ortholog to Smn1, Mus musculus
    ortholog to smn1, Danio rerio
    intraspecies paralog to SMN2
  • important member of the insulin-like growth factor (IGF) system
  • CATEGORY signaling cytokine growth factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,coiled bodies (Cajal)
  • generally located both in the cytoplasm and the nucleus where it is highly associated with gem-like (gemini of coiled bodies) structures
  • localizes diffusely throughout the cytoplasm, and in nuclear bodies called Cajal bodies, which are believed to be ribonucleoprotein (RNP) processing and storage sites
  • colocalizes in ribonucleoprotein granules within neurites and at growth cones
  • basic FUNCTION
  • inhibites the onset of apoptosis in NGF/dBcAMP-deprived or UV-treated co-differentiated PC12 cells by preventing cytochrome c release and caspase-3 activation, indicating that its effects are through suppression of the mitochondrial apoptotic pathway
  • role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development
  • role at the neuromuscular junction
  • plays a neuron-specific role during development
  • enhancer of apoptosis in malignant prostate cells
  • playing a key role in neurite outgrowth, via its possible involvement in nucleocytoplasmic and dendritic transport
  • important roles in RNA metabolism
  • SMN complex activity in snRNP assembly is regulated and point to a differential requirement for SMN function during development and cellular differentiation
  • being essential for the biogenesis of small nuclear RNA-ribonucleoproteins, the major components of the pre-mRNA splicing machinery
  • implicated in the biogenesis of the spliceosomal small nuclear ribonucleoproteins (snRNPs)
  • prolonging the half-life of the IGFs and altering their interaction with cell surface receptors, by binding to the first one
  • acting as an inhibitor of IGF-induced bone cell proliferation
  • acting as a transport protein for IGF-I and IGF-II and modulating their biological effects
  • being a novel dB-cAMP-induced anti-angiogenic and anti-tumorigenic mediator
  • enhancing cardiomyocyte differentiation
  • a role in axonogenesis
  • Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN down-regulation in motor neurons of SMA mouse embryos and in zebrafish
  • a key role for the SMN complex in RNA metabolism and in splicing regulation indicating that SMA is a general splicing disease that is not restricted to motor neurons
  • SMN1-GEMIN2 complex plays a role in homologous recombination, in addition to spliceosomal snRNP assembly
  • role of IGFBP4 in regulating IGF bioavailability
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, RNA splicing
    PHYSIOLOGICAL PROCESS development , locomotion , nervous system
  • regulation of cell growth
  • skeletal system development
    signaling signal transduction
    a component
  • part of the SMN complex (SMN protein and GEMIN2 to 7)
  • 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
  • SMN1-GEMIN2 complex constitutes part of the large SMN complex, which promotes the assembly of the spliceosomal small nuclear ribonucleoprotein (snRNP)
    RNA binding
    small molecule
  • proteins involved in the biogenesis of snRNPs
  • survival of motor neuron protein interacting protein 1, SIP1 (
  • B-cell CLL/lymphoma 2, BCL2 (
  • DEAD (Asp-Glu-Ala-Asp) box polypeptide 20, DDX20 (GEMIN3) (
  • STRAP to influencing intracellular localization of SMN1
  • SIN3A by its SIN3A-interacting domain to the exon 6 region
  • IGF2 more than IGF1
  • FZD8 and LRP6
  • DNA transactivator FUSE binding protein, FBP (
  • small nuclear ribonucleoprotein polypeptides B,-D1, and -D3
  • LSM4 homolog, U6 small nuclear RNA associated (S. cerevisiae), LSM4
  • LSM6 homolog, U6 small nuclear RNA associated (S. cerevisiae), LSM6
  • GAR1 (SMN1 interaction requires the arginine- and glycine-rich domains of both fibrillarin and GAR1 and is defective in SMN mutants found in some SMA patients) (
  • osteoclast stimulating factor 1, OSTF1
  • zinc finger protein ZPR1
  • hnRNP Q proteins
  • hnRNP-R and gry-rbp/hnRNP-Q (
  • coilin, COIL (
  • gem (nuclear organelle) associated protein 4, GEMIN4
  • gem (nuclear organelle) associated protein 5, GEMIN5 (
  • gem (nuclear organelle) associated protein 6, GEMIN6 (
  • gem (nuclear organelle) associated protein 7, GEMIN7 (
  • snurportin1, SNUPN and karyopherin (importin) beta 1, KPNB1
  • tumor suppressor protein p53, (
  • TAF4 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 135kDa, TAF4
  • protein phosphatase 4 (formerly X), catalytic subunit, PPP4C (
  • processing of precursor 7, ribonuclease P/MRP subunit (S. cerevisiae), POP7 (
  • transcription corepressor mSin3A (
  • profilin 1, PFN1
  • Lsm10 and Lsm11 (
  • fragile X mental retardation 1, FMR1
  • plastin 3, PLS3. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN down-regulation in motor neurons of SMA mouse embryos and in zebrafish
  • physically interacted with FZD8, and a Wnt co-receptor, LRP6, and inhibited the binding of WNT3A to FZD8 and LRP6
  • ELAVL4 interacts with SMN1 and can rescue spinal muscular atrophy-like neuronal defects
  • SMN1 is a novel target of ELK1, and the ETS motifs in the SMN1 promoter are involved in this regulation
  • GEMIN2 (
  • is directly interacting with profilin2a (PFN2 binds to a stretch of proline residues in SMN, which is heavily impaired by a novel SMN2 missense mutation)
  • interferes with the ROCK pathway via PFN2, providing a mechanistic basis to explain axonal defects in SMA pathogenesis
  • differentially inhibits angiogenesis induced by distinct growth factor signaling pathways as IGFBP4 inhibited FGF2- and IGF1-stimulated angiogenesis
  • SOX9 is a transcriptional regulator of IGFBP4 and SOX9-induced activation of IGFBP4 may be one of the mechanisms by which SOX9 suppresses cell proliferation and progression of colon cancer
  • PAPPA cleaves IGF binding protein IGFBP4 and IGFBP5
  • COPA is a SMN1-binding partner, implicating this protein complex in normal SMN1 function, and this interaction serves an important function in the growth and maintenance of motor neuron processes and may play a significant role in the pathogenesis of SMA
  • HNRNPM promotes exon 7 inclusion of SMN1 and SMN2 pre-mRNA through targeting an enhancer on exon 7 through recruiting U2AF2
  • cell & other
    repressed by late in posnatal life to a basal level, which is then maintained throughout life and this downregulation takes place in the spinal cord earlier than in the brain and coincides with the onset of myelination
    Other coregulated with SIP1
    transcriptional regulation during cellular differentiation and development
    gene modifier ZNF259
    corresponding disease(s) AMCSMA1 , SMA , SMA2 , SMA3 , SMA4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   amplification    
    abnormal gene copy number increases the susceptibility to amyotrophic lateral sclerosis
    Susceptibility to amyotrophic lateral sclerosis (ALS)
    Variant & Polymorphism other one copy of SMN1 was associated with an increased risk of developing ALS
    Candidate gene
    Therapy target use of single-stranded oligonucleotides to direct genetic conversion of SMN2 to SMN1 in human cells from SMA patients
  • Smn-/- mice died during the peri-implantation stage, whereas transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients
  • mouse lacking the C-terminus of SMN lack nuclear targeting in the motor neuron of the SMN protein
  • Drosophila smn mutant show abnormal motor behavior, excitatory post-synaptic currents are reduced while synaptic motor neuron boutons are disorganized indicating defects at the neuromuscular junction
  • Caenorhabditis elegans with deletion of smn-1 display locomotor dysfunction, late larval arrest, reduced lifespan sterility and impaired pharyngeal activity