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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
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