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FLASH GENE
Symbol FOXA1 contributors: mct - updated : 25-03-2015
HGNC name forkhead box A1
HGNC id 5021
Location 14q21.1      Physical location : 38.059.192 - 38.064.489
Synonym name
  • hepatocyte nuclear factor 3, alpha
  • transcription factor 3A
  • Synonym symbol(s) FKHL11A, FOXL1, HNF3A, TCF3A, MGC33105, HNF-3-alpha
    DNA
    TYPE functioning gene
    STRUCTURE 5.70 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC390468 14 similar to Plasmodium falciparum trophozoite antigen r45-like protein LOC390469 14 similar to interleukin enhancer binding factor 2 MBIP 14q13 similar to interleukin enhancer binding factor 2 LOC387985 14 hypothetical gene supported by AY102071 TITF1 14q13.1-q13.2 thyroid transcription factor 1 PHKBP2 14q13.2 phosphorylase kinase, beta pseudogene 2 NKX2-8 14q13.1-p13.2 NK2 transcription factor related, locus 8 (Drosophila) PAX9 14q12-q13.1 paired box gene 9 SLC25A21 14q11.2 solute carrier family 25 (mitochondrial oxodicarboxylate carrier), member 21 MIPOL1 14q13.3 solute carrier family 25 (mitochondrial oxodicarboxylate carrier), member 21 FOXA1 14q12-q13 forkhead box A1 TTC6 14q13.2 tetratricopeptide repeat domain 6 LOC387986 14 LOC387986 SSTR1 14q13.3 somatostatin receptor 1 C14orf27 14q13.3 chromosome 14 open reading frame 27 LOC390470 14 similar to KRT8 protein SEC23A 14q13.2 Sec23 homolog A (S. cerevisiae) PPIAP4 14 peptidylprolyl isomerase A (cyclophilin A) pseudogene 4 SIP1 14q13-q21 survival of motor neuron protein interacting protein 1 TRAPPC6B 14q13.3 trafficking protein particle complex 6B LOC390471 14 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) PNN 14q13 pinin, desmosome associated protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3124 - 472 - 2008 18336786[
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     liver    
     mouthtongue   
     stomach    
    Reproductivefemale systembreastmammary gland   Homo sapiensAdult
     male systemprostate  predominantly Homo sapiensAdult
    Respiratoryrespiratory tracttrachea  highly
    Urinarybladder    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text endodermal cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a forkhead (FH, winged helix) domain
  • two loops-wings on the C-terminal side of helix-turn-helix homeo domain
  • HOMOLOGY
    interspecies homolog to Drosophila homeo forkhead DNA binding domain
    Homologene
    FAMILY
  • protein-tyrosine phosphatase family
  • non-receptor class dual specificity subfamily
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • activator of gene expression in hepatocytes, respiratory and intestinal epithelia
  • cooperating with GRL to activate genes that code for proteins involved in glucose homeostasis, namely PEPCK (PCK1, PCK2), TAT, IGFBP1, unlikely to be a common cause of NIDDM
  • involved in mediating an estrogen response via ESR1
  • important regulator of MUC2 expression in the intestine
  • playing an important role in MUC2 mucin expression in the intestine during goblet cell differentiation
  • controls downstream transcription of oestrogen receptor (ER)-regulated genes
  • independent prognostic significance in breast cancer
  • cooperate with FOXA2 during liver and lung morphogenesis
  • up-regulating HSPA1A in MCF7 breast cancer cell line
  • regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner
  • role for HDAC7 and FOXA1 in estrogen repression of RPRM, a mechanism which could potentially be generalized to many more estrogen-repressed genes and hence be important in both normal physiology and pathological processes
  • critical for the androgenic regulation of prostate-specific promoters
  • directly regulates HOXB13 in human prostate epithelial cells
  • contributes to gene regulation by its ability to act as a pioneer factor that binds to nucleosomal DNA
  • critical for the androgenic regulation of prostate-specific promoters
  • major determinant of estrogen-ESR1 activity and endocrine response in breast cancer cells
  • sufficient to permit ESR1-chromatin interactions and transcriptional activity in diverse target tissues
  • plays a suppressive role in the early phase of adipogenesis, acting under the control of CEBPB, and might be involved in the regulation of the rate of progression of the early phase of adipogenesis
  • critical mediator of nuclear steroid receptor signalling, manifest at least in part through regulation of androgen receptor and oestrogen receptor activity
  • major role for FOXA1 in modulating nuclear steroid receptor activity in breast and prostate cancer, and FOXA1 may significantly contribute to pro-tumourigenic phenotypes
  • the role of FOXA1 in androgen signalling and prostate cancer is distinctly different from that in oestrogen signalling and breast cancer
  • required for postnatal survival due to its essential role in controlling pancreatic and renal function
  • play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue
  • potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways
  • FOXA1, FOXA2 are required for activation of SHH in the notochord
  • critical interacting partner of the nuclear hormone receptors, ESR1 and androgen receptor (AR), which are major drivers of the two most common cancers, namely breast and prostate cancer (
  • a later role for FOXA1, FOXA2 genes in regulating the maintenance of dopaminergic phenotype in mesodiencephalic dopaminergic (mDA) neurons
  • FOXA1 and FOXA2 control glucagon biosynthesis and secretion as well as alpha-cell differentiation with both common and unique target genes
  • FOXA1 recruits likely the chromatin modifier KMT2C to facilitate the deposition of H3K4me1 histone marks, subsequently demarcating active enhancer elements
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
    INTERACTION
    DNA
  • binding to HSPA1A promoter
  • RNA
    small molecule
    protein
  • interacts physically and functionally with NKX2-1 (interaction is inhibitory and occurs through the NKX2.1 homeodomain in a DNA-independent manner)
  • direct protein-protein interaction occurs between FOXA1 and androgen receptor
  • interaction with USF2 (interaction is mediated via the forkhead DNA-binding domain of FOXA1 and the DNA-binding domain of USF2)
  • binds at the same enhancer regions, where it functions as a pioneer factor to mediate ER association with compacted DNA
  • interaction with CTCF (can influence FOXA1 activity)
  • is a potent enhancer of NR3C1-induced transcription
  • NKX3-1, AR, and FOXA1 promote prostate cancer cell survival by directly upregulating RAB3B
  • represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake
  • FOXA1, but not ESR1, is essential for AHR-dependent regulation of CCNG2, assigning a role for FOXA1 in AHR action
  • FOXA1 binding leads to a decrease in nucleosome density at the CDKN2A promoter in senescent fibroblasts
  • KDM5B is required for GATA3 recruitment to the FOXA1 promoter to activate FOXA1 expression
  • NR5A2 cooperates with FOXA1 and binds directly to CDKN1A promoter and a distal regulatory region found at -62&
  • 8201;kb from its transcriptional start sites, allowing repression of CDKN1A transcription
  • TRPS1 acting as a transcription activator, directly induced FOXA1 transcription by binding to the FOXA1 promoter
  • FOXA1 recruits KMT2C to chromatin
  • FOXA1 is a negative regulator of SEMA3C and SEMA3C is a novel target of AR, GATA2, and FOXA1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal squamous cell carcinoma and in breast cancer
    tumoral     --low  
    is associated with better survival in the breast cancer
    constitutional       gain of function
    in both replicative and oncogene-induced senescence, and in turn activates transcription of CDKN2A through multiple mechanisms (
    tumoral somatic mutation      
    in prostate cancer
    Susceptibility to breast cancer
    Variant & Polymorphism SNP
  • many of the SNPs associated with breast cancer risk may be modulating the same biological process, namely, DNA affinity for FOXA1, a key regulator of ER activity
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    target fo breast cancer
    diabete  
    could be a novel therapeutic target for insulin resistance
    digestiveliver 
    could be a novel therapeutic target for nonalcoholic fatty liver disease
    ANIMAL & CELL MODELS