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Protein

Hepatocyte nuclear factor 3-alpha

Gene

Foxa1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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'. Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Involved in glucose homeostasis; activates the GCG promoter. 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. Modulates the transcriptional activity of nuclear hormone receptors. Is required for maximal gene activation mediated by AR in the prostate. Negatively regulates AR transactivation via competition with coactivators such as NCOA2. Is involved in ESR1-mediated transcription. 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.4 Publications

Regions

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

GO - Molecular functioni

  • double-stranded DNA binding Source: RGD
  • protein domain specific binding Source: RGD
  • sequence-specific DNA binding Source: RGD
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: MGI
  • transcription factor binding Source: MGI

GO - Biological processi

  • chromatin modification Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
Complete GO annotation...

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2807. Foxa1.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 466466Hepatocyte nuclear factor 3-alphaPRO_0000091794Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei303 – 3031PhosphoserineCombined sources
Modified residuei327 – 3271PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP23512.

PTM databases

iPTMnetiP23512.
PhosphoSiteiP23512.

Expressioni

Tissue specificityi

Liver.

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 (By similarity). Interacts with AR. Interacts with NR0B2.By similarity5 Publications

GO - Molecular functioni

  • protein domain specific binding Source: RGD
  • transcription factor binding Source: MGI

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009940.

Structurei

3D structure databases

ProteinModelPortaliP23512.
SMRiP23512. Positions 170-260.
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

eggNOGiKOG3563. Eukaryota.
COG5025. LUCA.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiP23512.
KOiK09387.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR013638. Fork-head_N.
IPR001766. Fork_head_dom.
IPR018533. Forkhead_box_C.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
PF08430. Forkhead_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P23512-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGTVKMEGH ESNDWNSYYA DTQEAYSSVP VSNMNSGLGS MNSMNTYMTM
60 70 80 90 100
NTMTTSGNMT PASFNMSYAN PGLGAGLSPG AVAGMPGGSA GAMNSMTAAG
110 120 130 140 150
VTAMGAALSP GGMGSMGAQP AASMNGLGPY AAAMNPCMSP MAYAPSNLGR
160 170 180 190 200
SRAGGGGDAK TFKRSYPHAK PPYSYISLIT MAIQQAPSKM LTLSEIYQWI
210 220 230 240 250
MDLFPYYRQN QQRWQNSIRH SLSFNACFVK VARSPDKPGK GSYWTLHPDS
260 270 280 290 300
GNMFENGCYL RRQKRFKCEK QPGAGGGSGG GGSKGVPENR KDPSGPVNPS
310 320 330 340 350
AESPIHRGVH GKASQLEGAP APGPAASPQT LDHSGATATG GGSELKSPAS
360 370 380 390 400
SSAPPISSGP GGWICTPLSP TWLAPHESQL HLKGAPHYSF NHPFSINNLM
410 420 430 440 450
SSSEQQHKLD FKAYEQALQY SPYGATLPAS LPLGGASVAT RSPIEPSALE
460
PAYYQGVYSR PVLNTS
Length:466
Mass (Da):48,775
Last modified:November 1, 1991 - v1
Checksum:i06555BA74BD9B7DC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55955 mRNA. Translation: CAA39418.1.
PIRiA36674.
RefSeqiNP_036874.1. NM_012742.1.
UniGeneiRn.10470.

Genome annotation databases

GeneIDi25098.
KEGGirno:25098.
UCSCiRGD:2807. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55955 mRNA. Translation: CAA39418.1.
PIRiA36674.
RefSeqiNP_036874.1. NM_012742.1.
UniGeneiRn.10470.

3D structure databases

ProteinModelPortaliP23512.
SMRiP23512. Positions 170-260.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009940.

PTM databases

iPTMnetiP23512.
PhosphoSiteiP23512.

Proteomic databases

PaxDbiP23512.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25098.
KEGGirno:25098.
UCSCiRGD:2807. rat.

Organism-specific databases

CTDi3169.
RGDi2807. Foxa1.

Phylogenomic databases

eggNOGiKOG3563. Eukaryota.
COG5025. LUCA.
HOGENOMiHOG000231817.
HOVERGENiHBG006621.
InParanoidiP23512.
KOiK09387.

Miscellaneous databases

PROiP23512.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR013638. Fork-head_N.
IPR001766. Fork_head_dom.
IPR018533. Forkhead_box_C.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
PF08430. Forkhead_N. 1 hit.
PF09354. HNF_C. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally."
    Lai E., Prezioso V.R., Smith E., Litvin O., Costa R.H., Darnell J.E. Jr.
    Genes Dev. 4:1427-1436(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 313-337 AND 413-434.
    Tissue: Liver.
  2. "The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and androgen receptor in transcriptional regulation of prostatic genes."
    Gao N., Zhang J., Rao M.A., Case T.C., Mirosevich J., Wang Y., Jin R., Gupta A., Rennie P.S., Matusik R.J.
    Mol. Endocrinol. 17:1484-1507(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PROSTATE AR ACTIVATION, INTERACTION WITH AR.
  3. "Orphan nuclear receptor small heterodimer partner represses hepatocyte nuclear factor 3/Foxa transactivation via inhibition of its DNA binding."
    Kim J.Y., Kim H.J., Kim K.T., Park Y.Y., Seong H.A., Park K.C., Lee I.K., Ha H., Shong M., Park S.C., Choi H.S.
    Mol. Endocrinol. 18:2880-2894(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH NR0B2.
  4. "Specific interactions of the wing domains of FOXA1 transcription factor with DNA."
    Cirillo L.A., Zaret K.S.
    J. Mol. Biol. 366:720-724(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DNA-BINDING, SUBUNIT.
  5. "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: FUNCTION, INTERACTION WITH NKX2-1.
  6. "Hepatocyte nuclear factor-3 alpha (HNF-3alpha) negatively regulates androgen receptor transactivation in prostate cancer cells."
    Lee H.J., Hwang M., Chattopadhyay S., Choi H.S., Lee K.
    Biochem. Biophys. Res. Commun. 367:481-486(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PROSTATE AR ACTIVATION, INTERACTION WITH AR.
  7. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiFOXA1_RAT
AccessioniPrimary (citable) accession number: P23512
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: July 6, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.