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P49698

- HNF4A_MOUSE

UniProt

P49698 - HNF4A_MOUSE

Protein

Hepatocyte nuclear factor 4-alpha

Gene

Hnf4a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 2 (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: MGI
    2. fatty acid binding Source: Ensembl
    3. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: InterPro
    4. protein binding Source: UniProtKB
    5. RNA polymerase II activating transcription factor binding Source: BHF-UCL
    6. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
    7. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
    8. sequence-specific DNA binding Source: MGI
    9. sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    10. steroid hormone receptor activity Source: InterPro
    11. transcription regulatory region DNA binding Source: BHF-UCL
    12. zinc ion binding Source: InterPro

    GO - Biological processi

    1. blood coagulation Source: Ensembl
    2. endocrine pancreas development Source: Reactome
    3. glucose homeostasis Source: BHF-UCL
    4. lipid metabolic process Source: MGI
    5. negative regulation of cell growth Source: Ensembl
    6. negative regulation of cell proliferation Source: Ensembl
    7. ornithine metabolic process Source: Ensembl
    8. phospholipid homeostasis Source: BHF-UCL
    9. positive regulation of cholesterol homeostasis Source: BHF-UCL
    10. positive regulation of transcription, DNA-templated Source: MGI
    11. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    12. regulation of gastrulation Source: MGI
    13. regulation of insulin secretion Source: BHF-UCL
    14. regulation of lipid metabolic process Source: Ensembl
    15. regulation of transcription, DNA-templated Source: MGI
    16. regulation of transcription from RNA polymerase II promoter Source: MGI
    17. response to glucose Source: BHF-UCL
    18. sex differentiation Source: MGI
    19. signal transduction involved in regulation of gene expression Source: MGI
    20. SMAD protein signal transduction Source: MGI
    21. transcription from RNA polymerase II promoter Source: GOC
    22. triglyceride homeostasis Source: BHF-UCL
    23. xenobiotic metabolic process Source: Ensembl

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_214529. Regulation of gene expression in beta cells.

    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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:109128. Hnf4a.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 474474Hepatocyte nuclear factor 4-alphaPRO_0000053559Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei142 – 1421PhosphoserineBy similarity
    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 – 4291Phosphothreonine1 Publication
    Modified residuei432 – 4321Phosphothreonine1 Publication
    Modified residuei436 – 4361PhosphoserineBy similarity
    Modified residuei458 – 4581N6-acetyllysineBy similarity

    Post-translational modificationi

    Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA By similarity.By similarity
    Acetylation at Lys-458 lowers transcriptional activation by about two-fold.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP49698.
    PaxDbiP49698.
    PRIDEiP49698.

    PTM databases

    PhosphoSiteiP49698.

    Expressioni

    Gene expression databases

    ArrayExpressiP49698.
    BgeeiP49698.
    CleanExiMM_HNF4A.
    GenevestigatoriP49698.

    Interactioni

    Subunit structurei

    Homodimerization is required for HNF4-alpha to bind to its recognition site. Interacts with PER2.1 Publication

    Protein-protein interaction databases

    BioGridi200354. 4 interactions.
    IntActiP49698. 3 interactions.
    MINTiMINT-5027670.

    Structurei

    3D structure databases

    ProteinModelPortaliP49698.
    SMRiP49698. Positions 58-377.
    ModBaseiSearch...
    MobiDBiSearch...

    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.
    GeneTreeiENSGT00740000115493.
    HOGENOMiHOG000260822.
    HOVERGENiHBG005606.
    InParanoidiP49698.
    KOiK07292.
    OMAiANTMPSH.
    PhylomeDBiP49698.
    TreeFamiTF352097.

    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: P49698-1) [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

    MRLSKTLAGM 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 DAPHTHHPLH PHLMQEHMGT 400
    NVIVANTMPS HLSNGQMCEW PRPRGQAATP ETPQPSPPSG SGSESYKLLP 450
    GAITTIVKPP SAIPQPTITK QEAI 474
    Length:474
    Mass (Da):52,684
    Last modified:May 29, 2007 - v2
    Checksum:i10843D528EAE87EE
    GO
    Isoform Short (identifier: P49698-2) [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):51,518
    Checksum:i4C293463C33B2D76
    GO

    Sequence cautioni

    The sequence BAA06101.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti55 – 551G → S in BAA06101. (PubMed:7999795)Curated
    Sequence conflicti365 – 3651K → R in BAE25624. (PubMed:16141072)Curated
    Sequence conflicti378 – 3781S → L in ABM69091. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei418 – 42811CEWPRPRGQAA → S in isoform Short. 1 PublicationVSP_003676Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D29015 mRNA. Translation: BAA06101.1. Different initiation.
    AY902317 Genomic DNA. Translation: AAX90602.1.
    AK143948 mRNA. Translation: BAE25624.1.
    AL591488 Genomic DNA. No translation available.
    BC039220 mRNA. Translation: AAH39220.1.
    EF193393 mRNA. Translation: ABM69091.1.
    CCDSiCCDS17012.1. [P49698-1]
    PIRiS52074.
    RefSeqiNP_032287.2. NM_008261.2. [P49698-1]
    XP_006498850.1. XM_006498787.1. [P49698-2]
    UniGeneiMm.202383.

    Genome annotation databases

    EnsembliENSMUST00000018094; ENSMUSP00000018094; ENSMUSG00000017950. [P49698-1]
    GeneIDi15378.
    KEGGimmu:15378.
    UCSCiuc008nta.2. mouse. [P49698-1]
    uc012cit.1. mouse. [P49698-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D29015 mRNA. Translation: BAA06101.1 . Different initiation.
    AY902317 Genomic DNA. Translation: AAX90602.1 .
    AK143948 mRNA. Translation: BAE25624.1 .
    AL591488 Genomic DNA. No translation available.
    BC039220 mRNA. Translation: AAH39220.1 .
    EF193393 mRNA. Translation: ABM69091.1 .
    CCDSi CCDS17012.1. [P49698-1 ]
    PIRi S52074.
    RefSeqi NP_032287.2. NM_008261.2. [P49698-1 ]
    XP_006498850.1. XM_006498787.1. [P49698-2 ]
    UniGenei Mm.202383.

    3D structure databases

    ProteinModelPortali P49698.
    SMRi P49698. Positions 58-377.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200354. 4 interactions.
    IntActi P49698. 3 interactions.
    MINTi MINT-5027670.

    PTM databases

    PhosphoSitei P49698.

    Proteomic databases

    MaxQBi P49698.
    PaxDbi P49698.
    PRIDEi P49698.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000018094 ; ENSMUSP00000018094 ; ENSMUSG00000017950 . [P49698-1 ]
    GeneIDi 15378.
    KEGGi mmu:15378.
    UCSCi uc008nta.2. mouse. [P49698-1 ]
    uc012cit.1. mouse. [P49698-2 ]

    Organism-specific databases

    CTDi 3172.
    MGIi MGI:109128. Hnf4a.

    Phylogenomic databases

    eggNOGi NOG241134.
    GeneTreei ENSGT00740000115493.
    HOGENOMi HOG000260822.
    HOVERGENi HBG005606.
    InParanoidi P49698.
    KOi K07292.
    OMAi ANTMPSH.
    PhylomeDBi P49698.
    TreeFami TF352097.

    Enzyme and pathway databases

    Reactomei REACT_214529. Regulation of gene expression in beta cells.

    Miscellaneous databases

    ChiTaRSi HNF4A. mouse.
    NextBioi 288038.
    PROi P49698.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49698.
    Bgeei P49698.
    CleanExi MM_HNF4A.
    Genevestigatori P49698.

    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. "Identification of two splice isoforms of mRNA for mouse hepatocyte nuclear factor 4 (HNF-4)."
      Hata S., Inoue T., Kosuga K., Nakashima T., Tsukamoto T., Osumi T.
      Biochim. Biophys. Acta 1260:55-61(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
      Strain: C57BL/6 X CBA.
      Tissue: Liver.
    2. "Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains."
      Farber C.R., Corva P.M., Medrano J.F.
      BMC Genomics 7:102-102(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: CAST/Ei.
      Tissue: Liver.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Kidney.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    5. "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: FVB/N.
      Tissue: Kidney.
    6. "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.
      Strain: C57BL/6.
      Tissue: Liver.
    7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-429 AND THR-432, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    8. "The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors."
      Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.
      Genes Dev. 24:345-357(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PER2.

    Entry informationi

    Entry nameiHNF4A_MOUSE
    AccessioniPrimary (citable) accession number: P49698
    Secondary accession number(s): A2A5I5
    , A2ICH0, Q3UNX3, Q8CFY1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: May 29, 2007
    Last modified: October 1, 2014
    This is version 141 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Binds fatty acids.By similarity

    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