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P35582

- FOXA1_MOUSE

UniProt

P35582 - FOXA1_MOUSE

Protein

Hepatocyte nuclear factor 3-alpha

Gene

Foxa1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 2 (01 Nov 1997)
      Previous versions | rss
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    Functioni

    Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' By similarity. Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas, lungs and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles. Plays a role in prostate morphogenesis and epithelial cell differentiation. FOXA1 and FOXA2 are essential for hepatic specification. FOXA1 and FOXA2 are required for morphogenesis and cell differentiation during formation of the lung. FOXA1 and FOXA2 are involved in bile duct formation; they positively regulate the binding of glucocorticoid receptor/NR3C1 to the IL6 promoter. FOXA1 and FOXA2 regulate multiple phases of midbrain dopaminergic neuron development; they regulate expression of NEUROG2 at the beginning of mDA neurogenesis and of NR4A2 and EN1 in immature mDA neurons. Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription. Inhibits NKX2-1-mediated transcription from the SFTPC promoter in lung epithel independently from DNA-binding. Involved in regulation of apoptosis. Involved in cell cycle regulation. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; activates the GCG promoter.By similarity9 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi169 – 26092Fork-headPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. sequence-specific DNA binding Source: MGI
    3. sequence-specific DNA binding transcription factor activity Source: MGI
    4. transcription regulatory region DNA binding Source: Ensembl

    GO - Biological processi

    1. anatomical structure formation involved in morphogenesis Source: MGI
    2. chromatin remodeling Source: UniProtKB
    3. connective tissue development Source: MGI
    4. dorsal/ventral neural tube patterning Source: MGI
    5. epithelial cell maturation involved in prostate gland development Source: MGI
    6. epithelial-mesenchymal signaling involved in prostate gland development Source: MGI
    7. epithelial tube branching involved in lung morphogenesis Source: MGI
    8. glucose homeostasis Source: MGI
    9. hormone metabolic process Source: MGI
    10. lung development Source: MGI
    11. lung epithelial cell differentiation Source: MGI
    12. negative regulation of epithelial to mesenchymal transition Source: Ensembl
    13. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    14. neuron fate specification Source: MGI
    15. positive regulation of intracellular estrogen receptor signaling pathway Source: Ensembl
    16. positive regulation of mitotic cell cycle Source: Ensembl
    17. positive regulation of neuron differentiation Source: MGI
    18. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
    19. positive regulation of smoothened signaling pathway Source: MGI
    20. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    21. prostate gland epithelium morphogenesis Source: MGI
    22. prostate gland stromal morphogenesis Source: MGI
    23. regulation of cell cycle Source: MGI
    24. regulation of gene expression Source: MGI
    25. response to estradiol Source: Ensembl
    26. secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development Source: MGI
    27. transcription, DNA-templated Source: UniProtKB-KW
    28. tube morphogenesis Source: MGI

    Keywords - Molecular functioni

    Activator, Chromatin regulator, Developmental protein, Repressor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hepatocyte nuclear factor 3-alpha
    Short name:
    HNF-3-alpha
    Short name:
    HNF-3A
    Alternative name(s):
    Forkhead box protein A1
    Gene namesi
    Name:Foxa1
    Synonyms:Hnf3a, Tcf-3a, Tcf3a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:1347472. Foxa1.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. microvillus Source: MGI
    2. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    The prostate shows a severely altered ductal pattern that resembles primitive epithelial cords surrounded by thick stromal layers; no differentiated or mature luminal epithelial cells are found. Dehydration and electrolyte imbalance, development of mild nephrogenic diabetes insipidus. Severe hypoglycemia due to at least in part diminished expression of GCG. Mice deficient for Fox1a and deficient for Foxa2 in the endoderm from E8.5 onwards do not show hepatic bud formation. Mice deficient for Fox1a and deficient for Foxa2 in the midbrain from E10.5 onwards show almost complete loss of mDA neurons. Mice deficient for Fox1a and deficient for Foxa2 in the embryonic liver show hyperplasia of the biliary tree due to at least in part activation of IL-6 expression, a proliferative signal for cholangiocytes.3 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 468468Hepatocyte nuclear factor 3-alphaPRO_0000091793Add
    BLAST

    Proteomic databases

    PRIDEiP35582.

    PTM databases

    PhosphoSiteiP35582.

    Expressioni

    Tissue specificityi

    Restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine). Expressed in the prostate.1 Publication

    Developmental stagei

    Most abundant in midgestation embryos (day 9.5). In embryonic lung expressed at E12 and E18 with highest levels in proximal airways and lowest levels in the distal lung.1 Publication

    Gene expression databases

    BgeeiP35582.
    CleanExiMM_FOXA1.
    GenevestigatoriP35582.

    Interactioni

    Subunit structurei

    Binds DNA as a monomer. Interacts with FOXA2. Interacts with NKX2-1. Interacts with HDAC7. Interacts with the histone H3-H4 heterodimer. Associates with nucleosomes containing histone H2A. Interacts with AR. Interacts with NR0B2 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi200351. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP35582.
    SMRiP35582. Positions 168-267.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni251 – 28838Essential for DNA bindingAdd
    BLAST

    Sequence similaritiesi

    Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5025.
    GeneTreeiENSGT00740000115483.
    HOGENOMiHOG000231817.
    HOVERGENiHBG006621.
    InParanoidiQ4VA63.
    KOiK09387.
    OMAiMNTMNTY.
    OrthoDBiEOG7C8GHD.
    PhylomeDBiP35582.
    TreeFamiTF316127.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR013638. Fork-head_N.
    IPR018533. Forkhead_box_C.
    IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF00250. Fork_head. 1 hit.
    PF08430. Fork_head_N. 1 hit.
    PF09354. HNF_C. 1 hit.
    [Graphical view]
    PRINTSiPR00053. FORKHEAD.
    SMARTiSM00339. FH. 1 hit.
    [Graphical view]
    PROSITEiPS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P35582-1 [UniParc]FASTAAdd to Basket

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    MLGTVKMEGH ESNDWNSYYA DTQEAYSSVP VSNMNSGLGS MNSMNTYMTM    50
    NTMTTSGNMT PASFNMSYAN TGLGAGLSPG AVAGMPGASA GAMNSMTAAG 100
    VTAMGTALSP GGMGSMGAQP ATSMNGLGPY AAAMNPCMSP MAYAPSNLGR 150
    SRAGGGGDAK TFKRSYPHAK PPYSYISLIT MAIQQAPSKM LTLSEIYQWI 200
    MDLFPYYRQN QQRWQNSIRH SLSFNDCFVK VARSPDKPGK GSYWTLHPDS 250
    GNMFENGCYL RRQKRFKCEK QPGAGGGSGG GGSKGGPESR KDPSGPGNPS 300
    AESPLHRGVH GKASQLEGAP APGPAASPQT LDHSGATATG GASELKSPAS 350
    SSAPPISSGP GALASVPPSH PAHGLAPHES QLHLKGDPHY SFNHPFSINN 400
    LMSSSEQQHK LDFKAYEQAL QYSPYGATLP ASLPLGSASV ATRSPIEPSA 450
    LEPAYYQGVY SRPVLNTS 468
    Length:468
    Mass (Da):48,854
    Last modified:November 1, 1997 - v2
    Checksum:i8513D17623D434FD
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti121 – 1211A → V in CAA52890. (PubMed:8034310)Curated
    Sequence conflicti307 – 3071R → W in CAA52890. (PubMed:8034310)Curated
    Sequence conflicti389 – 3891H → R in AAA86760. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X74936 mRNA. Translation: CAA52890.1.
    U44752 mRNA. Translation: AAA86760.1.
    BC096524 mRNA. Translation: AAH96524.1.
    CCDSiCCDS25926.1.
    PIRiA54258.
    RefSeqiNP_032285.2. NM_008259.3.
    XP_006515542.1. XM_006515479.1.
    XP_006515543.1. XM_006515480.1.
    XP_006515544.1. XM_006515481.1.
    XP_006515545.1. XM_006515482.1.
    XP_006515546.1. XM_006515483.1.
    UniGeneiMm.4578.

    Genome annotation databases

    EnsembliENSMUST00000044380; ENSMUSP00000041118; ENSMUSG00000035451.
    GeneIDi15375.
    KEGGimmu:15375.
    UCSCiuc007nps.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X74936 mRNA. Translation: CAA52890.1 .
    U44752 mRNA. Translation: AAA86760.1 .
    BC096524 mRNA. Translation: AAH96524.1 .
    CCDSi CCDS25926.1.
    PIRi A54258.
    RefSeqi NP_032285.2. NM_008259.3.
    XP_006515542.1. XM_006515479.1.
    XP_006515543.1. XM_006515480.1.
    XP_006515544.1. XM_006515481.1.
    XP_006515545.1. XM_006515482.1.
    XP_006515546.1. XM_006515483.1.
    UniGenei Mm.4578.

    3D structure databases

    ProteinModelPortali P35582.
    SMRi P35582. Positions 168-267.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200351. 2 interactions.

    PTM databases

    PhosphoSitei P35582.

    Proteomic databases

    PRIDEi P35582.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000044380 ; ENSMUSP00000041118 ; ENSMUSG00000035451 .
    GeneIDi 15375.
    KEGGi mmu:15375.
    UCSCi uc007nps.1. mouse.

    Organism-specific databases

    CTDi 3169.
    MGIi MGI:1347472. Foxa1.

    Phylogenomic databases

    eggNOGi COG5025.
    GeneTreei ENSGT00740000115483.
    HOGENOMi HOG000231817.
    HOVERGENi HBG006621.
    InParanoidi Q4VA63.
    KOi K09387.
    OMAi MNTMNTY.
    OrthoDBi EOG7C8GHD.
    PhylomeDBi P35582.
    TreeFami TF316127.

    Miscellaneous databases

    NextBioi 288026.
    PROi P35582.
    SOURCEi Search...

    Gene expression databases

    Bgeei P35582.
    CleanExi MM_FOXA1.
    Genevestigatori P35582.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR013638. Fork-head_N.
    IPR018533. Forkhead_box_C.
    IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF00250. Fork_head. 1 hit.
    PF08430. Fork_head_N. 1 hit.
    PF09354. HNF_C. 1 hit.
    [Graphical view ]
    PRINTSi PR00053. FORKHEAD.
    SMARTi SM00339. FH. 1 hit.
    [Graphical view ]
    PROSITEi PS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The HNF-3 gene family of transcription factors in mice: gene structure, cDNA sequence, and mRNA distribution."
      Kaestner K., Hiemisch H., Luckow B., Schuetz G.
      Genomics 20:377-385(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    2. Farrington S.M., Baron M.H.
      Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6.
    4. "Inactivation of the winged helix transcription factor HNF3alpha affects glucose homeostasis and islet glucagon gene expression in vivo."
      Kaestner K.H., Katz J., Liu Y., Drucker D.J., Schutz G.
      Genes Dev. 13:495-504(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION IN GLUCOSE HOMEOSTASIS.
    5. "Transcription factor FoxA (HNF3) on a nucleosome at an enhancer complex in liver chromatin."
      Chaya D., Hayamizu T., Bustin M., Zaret K.S.
      J. Biol. Chem. 276:44385-44389(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH NUCLEOSOMES.
    6. "Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4."
      Cirillo L.A., Lin F.R., Cuesta I., Friedman D., Jarnik M., Zaret K.S.
      Mol. Cell 9:279-289(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CHROMATIN OPENING, INTERACTION WITH HISTONES H3 AND H4.
    7. "Mild nephrogenic diabetes insipidus caused by Foxa1 deficiency."
      Behr R., Brestelli J., Fulmer J.T., Miyawaki N., Kleyman T.R., Kaestner K.H.
      J. Biol. Chem. 279:41936-41941(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    8. "Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation."
      Gao N., Ishii K., Mirosevich J., Kuwajima S., Oppenheimer S.R., Roberts R.L., Jiang M., Yu X., Shappell S.B., Caprioli R.M., Stoffel M., Hayward S.W., Matusik R.J.
      Development 132:3431-3443(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PROSTATE DEVELOPMENT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
    9. "FoxA1 binding to the MMTV LTR modulates chromatin structure and transcription."
      Holmqvist P.H., Belikov S., Zaret K.S., Wrange O.
      Exp. Cell Res. 304:593-603(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CHROMATIN OPENING.
    10. Cited for: FUNCTION IN LUNG DEVELOPMENT.
    11. "The initiation of liver development is dependent on Foxa transcription factors."
      Lee C.S., Friedman J.R., Fulmer J.T., Kaestner K.H.
      Nature 435:944-947(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN LIVER DEVELOPMENT.
    12. "Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner."
      Ferri A.L., Lin W., Mavromatakis Y.E., Wang J.C., Sasaki H., Whitsett J.A., Ang S.L.
      Development 134:2761-2769(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN NEURON DEVELOPMENT.
    13. "Physical and functional interactions between homeodomain NKX2.1 and winged helix/forkhead FOXA1 in lung epithelial cells."
      Minoo P., Hu L., Xing Y., Zhu N.L., Chen H., Li M., Borok Z., Li C.
      Mol. Cell. Biol. 27:2155-2165(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEVELOPMENTAL STAGE.
    14. "Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development."
      Gao N., LeLay J., Vatamaniuk M.Z., Rieck S., Friedman J.R., Kaestner K.H.
      Genes Dev. 22:3435-3448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PANCREAS DEVELOPMENT.
    15. "Foxa1 and Foxa2 regulate bile duct development in mice."
      Li Z., White P., Tuteja G., Rubins N., Sackett S., Kaestner K.H.
      J. Clin. Invest. 119:1537-1545(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN BILE DUCT DEVELOPMENT.

    Entry informationi

    Entry nameiFOXA1_MOUSE
    AccessioniPrimary (citable) accession number: P35582
    Secondary accession number(s): Q4VA63, Q61108
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: November 1, 1997
    Last modified: October 1, 2014
    This is version 133 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3