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FLASH GENE
Symbol SMN1 contributors: shn/npt/pgu - updated : 15-10-2013
HGNC name survival of motor neuron 1, telomeric
HGNC id 11117
Corresponding disease
AMCSMA1 arthrogryposis multiplex congenita-spinal muscular atrophy1
SMA spinal muscular atrophy, type 1
SMA2 spinal muscular atrophy, type 2, intermediate type
SMA3 spinal muscular atrophy, type 3
SMA4 spinal muscular atrophy, type 4
Location 5q13.2      Physical location : 69.345.349 - 70.248.836
Synonym name
  • gemin 1
  • component of gems 1
  • gemin-1
  • survival motor neuron protein
  • Synonym symbol(s) SMNT, BCD541, SMA@, SMN, SMA1, SMA, SMA2, SMA3, SMA4, T-BCD541
    DNA
    TYPE anonymous DNA segment
    SPECIAL FEATURE arranged in tandem
    text telomeric copy, part of an inverted duplicated region
    STRUCTURE 28.07 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • down-regulation of SMN promoter activity during cellular differentiation
  • potential binding sites for transcription factors ( Sp1, Ap1, zeste and RXRB )
  • nine amino acid motif within exon 2b, PAKKNKSQK, not only playing an integral role in Cajal body targeting, but also encoding the self-association domain.
  • MAPPING cloned Y linked N status confirmed
    Map cen - D5S1967 - D5S629 - SMN1 - D5S1999 - D5S637 - qter
    Physical map
    EEF1B3 5q12-q14 eukaryotic translation elongation factor 1 beta 3 PIK3R1 5q12-q13 phosphoinositide-3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) SLC30A5 5q12.1 solute carrier family 30 (zinc transporter), member 5 CCNB1 5q11-q12 cyclin B1 CENPH 5p15.2 centromere protein H MRPS36 5q13.3 mitochondrial ribosomal protein S36 CDK7 2p15-pcen cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase) KENAE 5q13.1 Kenae LOC285653 5q13.1 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein TAF9 5q12 TAF9 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 32kDa RAD17 5q12-q13.1 RAD17 homolog (S. pombe) FLJ30532 5q13.1 hypothetical protein FLJ30532 OCLN 5q13.1 occludin GTF2H2 5q13.1 general transcription factor IIH, polypeptide 2, 44kDa BIRC1 5q13.1 baculoviral IAP repeat-containing 1 SMN1 5q13.1 survival of motor neuron 1, telomeric LOC391791 5 similar to cadherin 12, type 2 preproprotein; Br-cadherin; cadherin-12; N-cadherin 2; brain-cadherin; neuronal cadherin 2; cadherin, neural type, 2 SMA3 5q13 SMA3 LOC389294 5 similar to bA110H4.2 (similar to membrane protein) LOC391792 5 similar to SMA3 protein LOC340089 5q13.2 similar to bA110H4.2 (similar to membrane protein) LOC391793 5 similar to cadherin 12, type 2 preproprotein; Br-cadherin; cadherin-12; N-cadherin 2; brain-cadherin; neuronal cadherin 2; cadherin, neural type, 2 SERF1A 5q13.1 small EDRK-rich factor 1A (telomeric) SMN2 5q13.1 survival of motor neuron 2, centromeric LOC389295 5 LOC389295 LOC389296 5 similar to Beta-glucuronidase precursor (Beta-G1) LOC389297 5 similar to bA110H4.2 (similar to membrane protein) LOC389298 5 similar to bA110H4.2 (similar to membrane protein) LOC389299 5 similar to Beta-glucuronidase precursor (Beta-G1) LOC391794 5 similar to cadherin 12, type 2 preproprotein; Br-cadherin; cadherin-12; N-cadherin 2; brain-cadherin; neuronal cadherin 2; cadherin, neural type, 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 1641 38 294 throughout cerebral and spinal cord areas - nucleoplasm and cytoplasm of both mature and developing motor neurons 1997 9302277
    An isoform of SMN comprising only the amino terminus (exons 13 and a part of intron 3) found only in axons (Setola et al, 2007)
    8 splicing 1545 28.3 262 throughout cerebral and spinal cord areas - nucleoplasm and cytoplasm of both mature and developing motor neurons 1997 9302277
  • lacking exon 5
  • - - - 18 - . axonal isoform detectable only during motoneuronal development and was down-regulated after birth . in spinal cord and brain 2007 17261814
  • stop codons truncating the reading frame shortly after the exon 3/intron 3 boundary; FL-SMN and a-SMN have identical N-terminal regions and diverge for the C-terminal tails
  • stimulates axonogenesis
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Nervousbrain   highly
     spinal cord   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
     fibroblast
    Lymphoid/Immunelymphocyte
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text predominantly, in tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    HOMOLOGY
    interspecies ortholog to Smn1, Rattus norvegicus
    ortholog to Smn1, Mus musculus
    ortholog to smn1, Danio rerio
    intraspecies paralog to SMN2
    Homologene
    FAMILY
  • important member of the insulin-like growth factor (IGF) system
  • CATEGORY signaling cytokine growth factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus,nucleoplasm,nuclear bodies,coiled bodies (Cajal)
    text
  • 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
    text
  • regulation of cell growth
  • skeletal system development
  • PATHWAY
    metabolism
    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)
  • INTERACTION
    DNA
    RNA binding
    small molecule
    protein
  • 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
    REGULATION
    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
    ASSOCIATED DISORDERS
    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
    Marker
    Therapy target use of single-stranded oligonucleotides to direct genetic conversion of SMN2 to SMN1 in human cells from SMA patients
    ANIMAL & CELL MODELS
  • 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