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P22449

- HNF4A_RAT

UniProt

P22449 - HNF4A_RAT

Protein

Hepatocyte nuclear factor 4-alpha

Gene

Hnf4a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 146 (01 Oct 2014)
      Sequence version 3 (29 May 2007)
      Previous versions | rss
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    Functioni

    Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi57 – 13276Nuclear receptorPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri60 – 8021NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri96 – 12025NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: RGD
    2. fatty acid binding Source: RGD
    3. fatty-acyl-CoA binding Source: RGD
    4. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: InterPro
    5. palmitoyl-CoA hydrolase activity Source: RGD
    6. protein binding Source: IntAct
    7. protein homodimerization activity Source: RGD
    8. repressing transcription factor binding Source: BHF-UCL
    9. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    10. sequence-specific DNA binding Source: RGD
    11. sequence-specific DNA binding transcription factor activity Source: RGD
    12. steroid hormone receptor activity Source: RGD
    13. transcription factor binding Source: RGD
    14. zinc ion binding Source: InterPro

    GO - Biological processi

    1. acyl-CoA metabolic process Source: RGD
    2. cell-cell junction organization Source: RGD
    3. cell differentiation Source: RGD
    4. establishment of tissue polarity Source: RGD
    5. negative regulation of cell proliferation Source: RGD
    6. negative regulation of mitotic cell cycle Source: RGD
    7. negative regulation of peptidyl-tyrosine phosphorylation Source: RGD
    8. negative regulation of protein import into nucleus, translocation Source: RGD
    9. negative regulation of sequence-specific DNA binding transcription factor activity Source: RGD
    10. negative regulation of tyrosine phosphorylation of Stat5 protein Source: RGD
    11. positive regulation of fatty acid biosynthetic process Source: RGD
    12. positive regulation of gluconeogenesis Source: RGD
    13. positive regulation of transcription, DNA-templated Source: BHF-UCL
    14. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    15. regulation of microvillus assembly Source: RGD
    16. regulation of transcription, DNA-templated Source: RGD
    17. response to cAMP Source: RGD
    18. response to drug Source: RGD
    19. response to glucose Source: RGD

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hepatocyte nuclear factor 4-alpha
    Short name:
    HNF-4-alpha
    Alternative name(s):
    Nuclear receptor subfamily 2 group A member 1
    Transcription factor 14
    Short name:
    TCF-14
    Transcription factor HNF-4
    Gene namesi
    Name:Hnf4a
    Synonyms:Hnf-4, Hnf4, Nr2a1, Tcf14
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2810. Hnf4a.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: RGD
    2. nucleus Source: BHF-UCL
    3. transcription factor complex Source: RGD

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi142 – 1432SS → AG: Loss of phosphorylation, no effect on DNA-binding. 1 Publication
    Mutagenesisi142 – 1432SS → LE: Loss of phosphorylation, no effect on DNA-binding. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 474474Hepatocyte nuclear factor 4-alphaPRO_0000053560Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei142 – 1421Phosphoserine; by PKA1 Publication
    Modified residuei143 – 1431Phosphoserine; by PKA1 Publication
    Modified residuei166 – 1661PhosphothreonineBy similarity
    Modified residuei167 – 1671PhosphoserineBy similarity
    Cross-linki234 – 234Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki307 – 307Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei313 – 3131Phosphoserine; by AMPKBy similarity
    Modified residuei429 – 4291PhosphothreonineBy similarity
    Modified residuei432 – 4321PhosphothreonineBy similarity
    Modified residuei436 – 4361PhosphoserineBy similarity
    Modified residuei458 – 4581N6-acetyllysineBy similarity

    Post-translational modificationi

    Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA By similarity. Phosphorylated in the recognition sequence R-R-S-S near the DNA-binding domain; phosphorylation results in decrease in DNA-binding activity. Phosphorylation of HNF4 depends on the diet and is decreased by a carbohydrate-rich diet and is increased by fasting.By similarity1 Publication
    The N-terminus is blocked.
    Acetylation at Lys-458 lowers transcriptional activation by about two-fold.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP22449.

    PTM databases

    PhosphoSiteiP22449.

    Expressioni

    Tissue specificityi

    Liver, kidney and intestine.

    Gene expression databases

    GenevestigatoriP22449.

    Interactioni

    Subunit structurei

    Homodimerization is required for HNF4-alpha to bind to its recognition site. Interacts with PER2.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Fabp1P026923EBI-5261592,EBI-1209448

    Protein-protein interaction databases

    BioGridi247763. 1 interaction.
    IntActiP22449. 3 interactions.

    Structurei

    Secondary structure

    1
    474
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi152 – 16413
    Helixi184 – 20320
    Helixi206 – 2094
    Helixi213 – 22210
    Helixi224 – 23411
    Turni235 – 2384
    Beta strandi239 – 2446
    Beta strandi250 – 2545
    Helixi256 – 2583
    Turni259 – 2613
    Helixi262 – 27110
    Helixi273 – 2797
    Helixi283 – 29412
    Helixi305 – 32420
    Beta strandi326 – 3283
    Helixi333 – 3386
    Helixi341 – 36020
    Helixi368 – 3736

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1M7WX-ray2.80A/B/C/D142-391[»]
    ProteinModelPortaliP22449.
    SMRiP22449. Positions 59-134, 151-376.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22449.

    Family & Domainsi

    Sequence similaritiesi

    Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri60 – 8021NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri96 – 12025NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG241134.
    HOGENOMiHOG000260822.
    HOVERGENiHBG005606.
    InParanoidiP22449.
    KOiK07292.
    PhylomeDBiP22449.

    Family and domain databases

    Gene3Di1.10.565.10. 1 hit.
    3.30.50.10. 1 hit.
    InterProiIPR003068. COUP_TF.
    IPR008946. Nucl_hormone_rcpt_ligand-bd.
    IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
    IPR001723. Str_hrmn_rcpt.
    IPR001628. Znf_hrmn_rcpt.
    IPR013088. Znf_NHR/GATA.
    [Graphical view]
    PfamiPF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view]
    PRINTSiPR01282. COUPTNFACTOR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTiSM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view]
    SUPFAMiSSF48508. SSF48508. 1 hit.
    PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Long (identifier: P22449-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MRLSKTLADM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGANLNS    50
    SNSLGVSALC AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR 100
    QCVVDKDKRN QCRYCRLKKC FRAGMKKEAV QNERDRISTR RSSYEDSSLP 150
    SINALLQAEV LSQQITSPIS GINGDIRAKK IANITDVCES MKEQLLVLVE 200
    WAKYIPAFCE LLLDDQVALL RAHAGEHLLL GATKRSMVFK DVLLLGNDYI 250
    VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYACLK AIIFFDPDAK 300
    GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ 350
    MIEQIQFIKL FGMAKIDNLL QEMLLGGSAS DAPHAHHPLH PHLMQEHMGT 400
    NVIVANTMPS HLSNGQMCEW PRPRGQAATP ETPQPSPPSG SGSESYKLLP 450
    GAITTIVKPP SAIPQPTITK QEAI 474
    Length:474
    Mass (Da):52,712
    Last modified:May 29, 2007 - v3
    Checksum:iE6DECA74FEA65E75
    GO
    Isoform Short (identifier: P22449-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         418-428: CEWPRPRGQAA → S

    Show »
    Length:464
    Mass (Da):51,546
    Checksum:i6B0961382FB9A0F7
    GO

    Sequence cautioni

    The sequence BAA01411.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence CAA40412.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti180 – 1801K → R in CAA40412. (PubMed:2279702)Curated
    Sequence conflicti183 – 1831N → S in CAA40412. (PubMed:2279702)Curated
    Sequence conflicti378 – 3781S → L in ABM69090. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei418 – 42811CEWPRPRGQAA → S in isoform Short. 2 PublicationsVSP_003677Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10554 mRNA. Translation: BAA01411.1. Different initiation.
    X57133 mRNA. Translation: CAA40412.1. Different initiation.
    EF193392 mRNA. Translation: ABM69090.1.
    PIRiA36471.
    S23502.
    RefSeqiNP_071516.2. NM_022180.2.
    UniGeneiRn.12238.

    Genome annotation databases

    GeneIDi25735.
    KEGGirno:25735.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10554 mRNA. Translation: BAA01411.1 . Different initiation.
    X57133 mRNA. Translation: CAA40412.1 . Different initiation.
    EF193392 mRNA. Translation: ABM69090.1 .
    PIRi A36471.
    S23502.
    RefSeqi NP_071516.2. NM_022180.2.
    UniGenei Rn.12238.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1M7W X-ray 2.80 A/B/C/D 142-391 [» ]
    ProteinModelPortali P22449.
    SMRi P22449. Positions 59-134, 151-376.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 247763. 1 interaction.
    IntActi P22449. 3 interactions.

    PTM databases

    PhosphoSitei P22449.

    Proteomic databases

    PRIDEi P22449.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 25735.
    KEGGi rno:25735.

    Organism-specific databases

    CTDi 3172.
    RGDi 2810. Hnf4a.

    Phylogenomic databases

    eggNOGi NOG241134.
    HOGENOMi HOG000260822.
    HOVERGENi HBG005606.
    InParanoidi P22449.
    KOi K07292.
    PhylomeDBi P22449.

    Miscellaneous databases

    EvolutionaryTracei P22449.
    NextBioi 607871.
    PROi P22449.

    Gene expression databases

    Genevestigatori P22449.

    Family and domain databases

    Gene3Di 1.10.565.10. 1 hit.
    3.30.50.10. 1 hit.
    InterProi IPR003068. COUP_TF.
    IPR008946. Nucl_hormone_rcpt_ligand-bd.
    IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
    IPR001723. Str_hrmn_rcpt.
    IPR001628. Znf_hrmn_rcpt.
    IPR013088. Znf_NHR/GATA.
    [Graphical view ]
    Pfami PF00104. Hormone_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view ]
    PRINTSi PR01282. COUPTNFACTOR.
    PR00398. STRDHORMONER.
    PR00047. STROIDFINGER.
    SMARTi SM00430. HOLI. 1 hit.
    SM00399. ZnF_C4. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48508. SSF48508. 1 hit.
    PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily."
      Sladek F.M., Zhong W., Lai E., Darnell J.E. Jr.
      Genes Dev. 4:2353-2365(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), PARTIAL PROTEIN SEQUENCE.
      Tissue: Liver.
    2. "A novel isoform of rat hepatocyte nuclear factor 4 (HNF-4)."
      Hata S., Tsukamoto T., Osumi T.
      Biochim. Biophys. Acta 1131:211-213(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), ALTERNATIVE SPLICING.
      Strain: Wistar.
      Tissue: Liver.
    3. "Expression of HNF4 alpha 3 in pancreatic islets and Ins-1 beta cells."
      Huang J., Karakucuk V., Levitsky L.L., Rhoads D.B.
      Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-378 (ISOFORMS LONG AND SHORT).
      Strain: New England Deaconess Hospital.
      Tissue: Liver.
    4. "Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4."
      Viollet B., Kahn A., Raymondjean M.
      Mol. Cell. Biol. 17:4208-4219(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS, PHOSPHORYLATION AT SER-142 AND SER-143.
    5. "Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand."
      Dhe-Paganon S., Duda K., Iwamoto M., Chi Y.I., Shoelson S.E.
      J. Biol. Chem. 277:37973-37976(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 142-391, FATTY ACID BINDING.

    Entry informationi

    Entry nameiHNF4A_RAT
    AccessioniPrimary (citable) accession number: P22449
    Secondary accession number(s): A2ICG9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: May 29, 2007
    Last modified: October 1, 2014
    This is version 146 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    DNA-binding activity of phosphorylated protein is reduced by fasting and by inducers of intracellular cyclic AMP.
    Binds fatty acids.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3