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FLASH GENE
Symbol ONECUT1 contributors: mct - updated : 04-01-2023
HGNC name one cut domain, family member 1
HGNC id 8138
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
Urinarykidney     Homo sapiens
Visualeyeretina    Mus musculusFetal
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Nervouscentral    Homo sapiensFetal
Nervousperipherous    Homo sapiensFetal
cells
SystemCellPubmedSpeciesStageRna symbol
Digestivehepatocyte
Endocrineislet cell (alpha,beta...)
Visualganglion cell Homo sapiens
Visualhorizontal association cell Homo sapiens
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,chromatin/chromosome
    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
  • ONECUT1, ONECUT2 redundantly regulate early retinal cell fates during development
  • ONECUT1 transcription factor is a factor that influences the gene regulatory networks specific to cones and rods, but not those that are common to both.
  • is an important regulator of both duct and acinar cell development in the embryonic pancreas
  • ONECUT1, ONECUT2 are involved in dose-dependent regulation of retinal horizontal cell fate
  • OTX2, ONECUT1 and possibly other Onecut proteins have likely a broad role in coordinating cone development and function
  • controls a transcriptional and epigenetic machinery regulating endocrine development, involved in a spectrum of diabetes
  • is a crucial fate regulator in pancreas progenitors and likely is also involved in preparing pancreatic progenitors for later endocrine specification
  • 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) PHGAD
    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