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FLASH GENE
Symbol PDX1 contributors: mct/pgu - updated : 04-10-2014
HGNC name pancreatic and duodenal homeobox 1
HGNC id 6107
Corresponding disease
MODY4 maturity onset diabetes of the young, type IV
PHYC pancreatic hypoplasia congenital
Location 13q12.2      Physical location : 28.494.167 - 28.500.451
Synonym name
  • somatostatin transactivating factor 1
  • insulin promoter factor 1, homeodomain transcription factor
  • pancreatic-duodenal homeobox factor 1
  • glucose- sensitive factor
  • pancreatic-duodenal homeobox factor 1
  • pyruvate dehydrogenase complex, component X
  • islet/duodenum homeobox-1
  • Synonym symbol(s) STF1, IDX1, IUF1, IPF1, GSF, MODY4, PAGEN1, PDX-1, STF-1
    DNA
    TYPE functioning gene
    STRUCTURE 6.28 kb     2 Exon(s)
    regulatory sequence Promoter
    Binding site   enhancer   HRE
    text structure
  • a region of the promoter between - 2715 and - 1960 which was essential to direct pancreatic islet-cell-specific expression
  • GG2 element, despite its divergence from the core homeodomain consensus binding motif, is a site for IPF1 activation in the insulin gene
  • a proximal E-box, located at 105 bp is highly conserved between species,and has been proposed to confer beta-cell specificity to the PDX1 promoter
  • ATF3-responsive element in the PDX1 promoter
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2573 30.6 283 - 1996 8635654
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestineduodenum highly Homo sapiensAdult
     intestinelarge intestinecolon  
     stomach   highly Homo sapiens
    Endocrinepancreas   highly Homo sapiensAdult
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningepidermisstratum basale 
    Epithelialsecretoryglandularendocrine  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    cell lineage down-regulated in the ductal and acinar cell lineages
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal transactivation domain
  • an homeodomain responsible for DNA binding
  • a nuclear localization signal (NLS)
  • a conserved C terminus that is mutated in human diabetes
  • HOMOLOGY
    interspecies homolog to murine Pax1
    Homologene
    FAMILY
  • ANTP homeobox family
  • IPF1/XlHbox-8 subfamily
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • key regulator of pancreatic islet development and insulin gene transcription
  • involved in islet beta cell function and formation
  • playing a critical role for the initiation of all pancreatic lineages
  • may inhibit the ductal differentiation program in the pancreatic endocrine compartment, particularly beta cells
  • transcription factor, necessary for differentiation of exocrine and endocrine pancreas, and regulating insulin gene transcription
  • regulates cell proliferation and invasion in human pancreatic cancer cells
  • plays a crucial role in pancreas development and beta-cell differentiation, and maintaining mature beta-cell function
  • functions as a putative tumor suppressor in gastric cancer
  • transcription factor that critically regulates early pancreas formation and multiple aspects of mature beta cell function, including insulin secretion, mitochondrial metabolism, and cell survival
  • homeodomain transcription factor, that serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity
  • recruits EP300 and enhances the transcriptional activity of PDX1, which results in the stimulation of insulin secretion in response to high glucose levels
  • MAFA, PDX1 and NEUROG3 (an upstream regulator of Beta2/NEUROD1) leads to the effective reprogramming of acinar cells into insulin-producing beta cells
  • is not necessary for the postnatal formation of &
  • 946;-cells but is essential for their full maturation to glucose-responsive beta-cells
  • key regulator of pancreas and foregut development
  • key role in maintaining the integrity and function of insulin-secreting beta cells in the adult pancreas
  • PDX1, NEUROG3 and MAFA, are very important in pancreatic development
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • WIFTCF3 and NEUROD1
  • negatively regulates the pancreatic ductal cell-specific keratin 19 promoter
  • interacting with SPOP (targets PDX1 for ubiquitination and proteasomal degradation
  • substrate for protein CSNK2A1
  • potential role for NKX6-1 in promoting PDX1 reprogrammed cells maturation along the beta-cell-like lineage
  • ATF2 interacts with beta-cell-enriched transcription factors, MAFA, PDX1, and NEUROD1, and activates insulin gene transcription
  • RB1 associates with and stabilizes pancreatic duodenal homeobox-1 (PDX1) that is essential for embryonic pancreas development and adult beta-cell function
  • ATF3 interacted with PDX1, and effectively inhibited EP300-mediated transcriptional coactivation of the PBE-containing promoter, whereas C-terminal domain-deleted ATF3 did not inhibit the transcoactivation of EP300
  • PDX1 is important for GPR27 effect on the insulin promoter and insulin secretion
  • key role of PPARG in regulating pancreatic beta-cell function by improving the stability of PDX1 and MAFA proteins
  • PDX1 contributes to the transcriptional transactivation of ALX3 in pancreatic beta-cells by acting in co-ordination with USF1 and USF2 (pMID: 25040025)
  • cell & other
    REGULATION
    inhibited by C20orf67 (interaction that may regulate normal beta cell differentiation)
    ATF3, that negatively regulated PDX1 expression in pancreatic beta-cells
    repressed by MLXIPL
    Other regulated by HNF1A and HNF3B
    regulated by glucose, GLP-1, insulin, T(3), HB-EGF, and TNF-alpha in pancreatic beta cells
    regulation of its expression by FOXA1 and FOXA2 is a key early event controlling the expansion and differentiation of the pancreatic primordia
    regulated by MAFA, MAFB (regulate PDX1 transcription in pancreatic beta cells)
    regulated by KLF11
    ASSOCIATED DISORDERS
    corresponding disease(s) MODY4 , PHYC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer / benign prostate tissue
    constitutional       loss of function
    with MAFA in beta-cells of diabetic patient (leads to suppression of insulin biosynthesis and secretion)
    constitutional       loss of function
    leads to a failure of &946; cell compensation for insulin resistance at least in part by impairing critical functions of the ER
    constitutional     --low  
    gastric expression is down-regulated in H. pylori infection and incisural antralisation
    tumoral     --low  
    in intestinal metaplasia
    tumoral     --low  
    in gastric cancer
    constitutional     --low  
    plays an important role in development of type 2 diabetes
    constitutional germinal mutation      
    Biallelic PDX1 mutations causing neonatal diabetes without exocrine pancreatic insufficiency
    Susceptibility for early and late-onset type 2 diabetes
    Variant & Polymorphism other polymorphisms increasing the risk of late-onset type 2 diabetes
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    down-regulation of PDX1 expression inhibits pancreatic cancer cell growth implying its use as a potential therapeutic target for the treatment of pancreatic cancer
    diabete  
    PDX1 regulation of ER homeostasis is a potential therapeutic target for type 2 diabetes
    ANIMAL & CELL MODELS