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FLASH GENE
Symbol PABPN1 contributors: mct/shn - updated : 20-12-2014
HGNC name poly(A) binding protein, nuclear 1
HGNC id 8565
Corresponding disease
OPMD oculopharyngeal muscular dystrophy
Location 14q11.2      Physical location : 23.789.396 - 23.795.367
Synonym name
  • polyadenylate-binding protein 2
  • poly(A)-binding protein, nuclear 1
  • oculopharyngeal muscular dystrophy
  • Synonym symbol(s) PABP2, PAB2, PABP-2, PABII, OPMD, PABII, Poly
    DNA
    TYPE functioning gene
    STRUCTURE 5.98 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence
    text structure a 5' polymorphic,unstable GCG (alanine) repeat, from 6 to 8-13 copies
    MAPPING cloned Y linked N status confirmed
    Map cen - D14S283 - D14S990 - PABPN1 - D14S581 - D14S972 - qter
    RNA
    TRANSCRIPTS type messenger
    text multiple splice variants
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 3080 32.7 306 - 2008 18343218
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Nervousbrain    
     nerve   highly
    Reproductivemale systemprostate   
     male systemtestis  highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an acidic N terminal domain with trinucleotide expansion, with possible role in PABPN1 nucleo-cytoplasmic transport
  • one putative RNA binding domain of the RNP type
  • a C terminal basic domain
  • mono polymer complex
    HOMOLOGY
    interspecies ortholog to Pabpn1, Mus musculus
    ortholog to Pabpn1, Rattus norvegicus
    ortholog to PABPN1, Pan troglodytes
    ortholog to pabpn1, danio rerio
    Homologene
    FAMILY
    CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,nucleolus
    text
  • germinal center of lymph nodule
  • possible role of the N-terminal polyalanine tract in PABPN1 nucleo-cytoplasmic transport
  • basic FUNCTION
  • required for progressive and efficient polymerization of poly(A) tail on the 3' end and controlling its size to abot 240 nucleotides
  • involved in muscular contraction
  • provides some protection to cells against pro-apoptotic insults distinct from the OPMD mutation such as staurosporine treatment and Bax expression
  • likely exerting its anti-apoptotic effect through the regulation of BIRC4 levels
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CPSF (160, 100, 73, 30)/PARN/PABPN1
  • INTERACTION
    DNA
    RNA binds with high affinity to nascent poly(A) tails
    small molecule
    protein
  • SKIP
  • CARM1
  • hnRNP A1 and hnRNP A/B
  • CPSF1, binding the polyadenylation signal AAUAAA, and PABPN1, binding the growing poly(A) tail, cooperatively stimulate poly(A) polymerase such that a complete poly(A) tail is synthesized in one processive event, which terminates at a length of approximately 250 nucleotides
  • ARIH2 E3-ligase regulates PABPN1 protein accumulation and aggregation
  • cell & other
    REGULATION
    Other upregulating MYOD1
    ASSOCIATED DISORDERS
    corresponding disease(s) OPMD
    Susceptibility
    Variant & Polymorphism repeat polyalanine expansion leading to the formation of nuclear aggregates (intranuclear inclusions)
    Candidate gene
    Marker
    Therapy target
  • anti-aggregation therapy (trehalose), reducing aggregate formation, may prove effective in the treatment of OPMD
  • a single-domain intracellular antibody, preventing oculopharyngeal muscular dystrophy-associated aggregation of nuclear polyA-binding protein
  • Sir2 and AMPK inhibition as therapeutic strategies for muscle protection in OPMD
  • Wild-type PABPN1 over-expression can reduce mutant PABPN1 toxicity in both cell and mouse models of OPMD
  • ANIMAL & CELL MODELS
  • Transgenic miceexpressing high levels of expanded hPABPN1 with a 13-alanine stretch showed an apparent myopathy phenotype, especially in old age
  • PABPN1 knockdown makes cells more susceptible to apoptotic stimuli
  • transcriptomic analysis revealed a massive gene deregulation in mouse model of OPMD (A17.1), display a significant deregulation of pathways associated with muscle atrophy