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FLASH GENE
Symbol ONECUT1 contributors: mct - updated : 11-04-2013
HGNC name one cut domain, family member 1
HGNC id 8138
Location 15q21.3      Physical location : 53.049.352 - 53.082.209
Synonym name
  • Hepatocyte nuclear factor 6
  • Synonym symbol(s) HNF6, HNF6A, OC-1
    DNA
    TYPE functioning gene
    STRUCTURE 32.86 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text two isoforms with different DNA binding properties
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1925 - 465 - 1998 9593691
    HNF-6 alpha
    - splicing - - 491 - 1998 9593691
    insertion in the linker domains
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver     Homo sapiensFetal
    Endocrinepancreas     Homo sapiensFetal
    Nervousspinal cordanterior horn    Homo sapiensFetal
    Reproductivemale systemtestis  lowly
    Visualeyeretina    Mus musculusFetal
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral    Homo sapiensFetal
    Nervousperipherous    Homo sapiensFetal
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestivehepatocyte
    Endocrineislet cell (alpha,beta...)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a polyglutamine tract
  • a STP box
  • a polyhistidine tract
  • a Drosophila cut-like
  • a peculiar helix-turn-helix (homeo)-DNA binding domain, bipartite onecut-homeodomain sequence
  • mono polymer monomer
    HOMOLOGY
    interspecies ortholog to rattus Onecut1
    ortholog to murine Onecut1
    intraspecies paralog to ONECUT2, ONECUT3
    Homologene
    FAMILY Onecut (OC) family of transcription factors
    CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    text utilizes the bipartite onecut-homeodomain sequence to localize ONECUT1 protein to the nuclear compartment
    basic FUNCTION
  • regulator of hepatocyte specific genes
  • may be involved in epithelial cell differentiation of gut endoderm
  • participating to the control of organ development from the forgut and midgut endoderm
  • inhibiting the glucocorticoid-induced stimulation of two genes of the glucose metabolism
  • stimulating hepatocyte nuclear factor 3B and TTR promoter
  • antagonizing 6 phosphofructo-2-kinase (PFKFB1), PEPCK (PCK1, PCK2)
  • ONECUT2 and ONECUT3 play redundant roles with ONECUT1 in pancreas development
  • required during embryogenesis for pancreatic specification, morphogenesis and endocrine differentiation
  • key regulatory factor in pancreatic development, endocrine differentiation and the formation of the biliary tract, as well as glucose metabolism
  • has both early and late functions in the developing pancreas and is essential for maintenance of NEUROG3 expression and proper pancreatic duct morphology
  • one of liver-enriched transcription factors
  • its function is correlated to cell proliferation, cell cycle regulation, cell differentiation and organogenesis, cell migration and cell-matrix adhesion, glucose metabolism, bile homeostasis, inflammation
  • ONECUT1, ONECUT2, ONECUT3 are required at early developmental stages for differentiation of the mesencephalic trigeminal nucleus neurons that are in turn necessary for maintenance of the Locus Coeruleus
  • role in the control of normal beta cell differentiation and its involvement in beta cell dysfunction under diabetic conditions by suppressing MAFA gene expression
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
    INTERACTION
    DNA
  • binding to the consensus sequence 5'-DHWATTGAYTWWD-3' on a variety of gene promoters such as those of HNF3B and TTR
  • RNA
    small molecule
    protein
  • is a novel target of NR0B2 in the regulation of gluconeogenesis
  • in developing pancreas, directly activates the pro-endocrine transcription factor, NEUROG3
  • binds to specific DNA sequences of numerous target gene promoters
  • GLIS3 can interact directly with ONECUT1 (N-terminus in GLIS3 and the homeodomain of ONECUT1 are critical for this interaction)
  • ONECUT1 and ONECUT2 transcription factors are the missing hemophilia B Leyden regulators that operate through the -5/-6 site
  • suppresses the promoter activity of MAFA through the FOXA2-binding cis-element on the MAFA enhancer region (named area A)
  • ONECUT1 interacts with LMX1A to promote ventral midbrain neural stem cells (vmNSCs)differentiation into dopamine neuron through WNT1-LMX1A pathway
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in pancreatic cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • ONECUT1 and SOX9 are new biomarkers of acinar-to-ductal metaplasia (ADM) and constitute candidate targets for preventive treatment in cases when ADM may lead to cancer
  • Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    HNF6-mediated pathways represent attractive therapeutic targets for the treatment of the relative diseases such as cholestasis
    ANIMAL & CELL MODELS
  • mice deficient in ONECUT1, ONECUT2, or both exhibit depleted levels of F9