Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol LIN28A contributors: mct/ - updated : 12-02-2015
HGNC name lin-28 homolog A (C. elegans)
HGNC id 15986
Location 1p36.11      Physical location : 26.737.268 - 26.756.218
Synonym name
  • RNA-binding protein LIN-28
  • zinc finger, CCHC domain containing 1
  • lin-28 homolog
  • protein lin-28 homolog A
  • Synonym symbol(s) LIN-28, FLJ12457, ZCCHC1, CSDD1, LIN28
    DNA
    TYPE functioning gene
    STRUCTURE 18.95 kb     4 Exon(s)    1 Copie(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 4014 - 209 - 2009 19578360
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegerm cell Homo sapiensFetal
    cell lineage
    cell lines ovarian cancer, pluripotent germ cell tumor (NT2, PA-1)
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text placenta and early embryonal cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a PIN domain
  • a cold-shock DNA binding (CSD) domain
  • a GGAGA(U) motif within LIN28A mRNA-binding sites
  • HOMOLOGY
    interspecies homolog to murine Lin28
    intraspecies paralog to LIN28B
    Homologene
    FAMILY
  • lin-28 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus,nucleolus
    text
  • abundant in undifferentiated cells
  • accumulates in the nucleus, suggesting that it normally shuttles from nucleus to cytoplasm bound to RNA
  • is localized to the periendoplasmic reticulum (ER) area and inhibits translation of mRNAs that are destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins
  • basic FUNCTION
  • has an important developmental role
  • involved in translation or RNA processing
  • influences the translation or stability of specific mRNAs during differentiation
  • may be a natural target for microRNA mediated regulation
  • act mainly in the cytoplasm by inducing uridylation of precursor let-7 (pre-let-7) at its 3prime end
  • Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis
  • negative regulator of let-7 microRNA processing, essential for proper primordial germ cells development
  • mediates post-transcriptional regulation of POU5F1 expression in embryonic stem cells by direct binding to POU5F1 mRNA
  • in mice may coordinate the rapid growth and metabolism of early embryogenesis and in turn delay the phenotypes associated with adulthood
  • LIN28A and LIN28B are important and essential regulators of glucose homeostasis
  • is both necessary and sufficient to influence glucose metabolism through the regulation of insulin-PI3K-MTOR signaling
  • LIN28A/LIN28B may regulate metabolism through direct mRNA-binding as well as MIRLET7A1 targets
  • important roles for this protein in the maintenance of the germline stem cell state and the regulation of microRNA activity in the developing human ovary
  • is reactivated in about 10p100 of epithelial tumors and promotes cell cycle progression by regulation of both mRNA translation (let-7-independent) and miRNA biogenesis (let-7-dependent)
  • is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis
  • important regulatory functions of LIN28A via direct mRNA interactions
  • plays important roles in development, stem cell maintenance, oncogenesis and metabolism
  • LIN28A-dependent stimulation of translation of target mRNAs may, in part, serve to compensate for their intrinsic instability, thereby ensuring optimal levels of expression of genes critical for cell viability, metabolism and pluripotency
  • role of LIN28A as a global suppressor of genes in the secretory pathway
  • is an essential factor of nucleologenesis during early embryonic development
  • role for LIN28A in prostate carcinoma development and activation of the AR axis
  • has a functional role in regulating trophoblast differentiation and function
  • RNA-binding protein expressed during embryogenesis, playing roles in development, pluripotency, and metabolism
  • enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics
  • LIN28A, LIN28B are novel regulators of innate immune function and new proteins of interest in Mast cells (MCs) disease
  • LIN28A and LIN28B have overlapping functions in temporally regulating neural progenitor cells (NPCs) proliferation during early brain development
  • LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency
  • in human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs)
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
  • LIN28A preferentially interacts directly with mRNA transcripts at GGAGA(U) sequence motifs within regions of unpaired secondary structure
  • LIN28A autoregulation by direct binding to its own mRNA
  • small molecule
    protein
  • promote malignancy by inhibiting MIRLET7A1 biogenesis
  • DROSHA mediates destabilization of LIN28A mRNA targets
  • binds to BMP4 mRNA in epithelial ovarian carcinoma cells, thereby promoting BMP4 expression at the post-transcriptional level
  • bound to and enhanced the translation of mRNAs for several metabolic enzymes, thereby increasing glycolysis and oxidative phosphorylation (OxPhos)
  • LARP7 interacts with a poly(A) polymerase TUT1 to maintain LIN28A mRNA stability
  • might play a crucial role in sustaining stemness and chemoresistance of liver cancer stem cells (CSCs) via LIN28A-dependent manner in hepatocellular crcinoma
  • cell & other
    REGULATION
    Other its down-regulation is required for/or a consequence of cell differenciation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in primary tumors and cancer cell lines and overexpression is linked to repression of let-7 family miRNAs and derepression of let-7 targets
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    enhancing LIN28A function or abrogating MIRLET7A1 may be therapeutically promising for diseases like obesity and diabetes
    ANIMAL & CELL MODELS
  • Lin28a transgenic mice have increased body size, a phenotype associated with genetic variation in the human LIN28B locus
  • muscle-specific loss of Lin28a or overexpression of Mirlet7a1 results in insulin resistance and impaired glucose tolerance