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P22361

- HNF1A_MOUSE

UniProt

P22361 - HNF1A_MOUSE

Protein

Hepatocyte nuclear factor 1-alpha

Gene

Hnf1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 149 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi199 – 27981Homeobox; HNF1-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB
    2. double-stranded DNA binding Source: Ensembl
    3. protein binding Source: UniProtKB
    4. protein dimerization activity Source: UniProtKB
    5. protein heterodimerization activity Source: MGI
    6. protein homodimerization activity Source: MGI
    7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
    8. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
    9. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    10. transcription regulatory region DNA binding Source: UniProtKB

    GO - Biological processi

    1. bile acid and bile salt transport Source: MGI
    2. bile acid biosynthetic process Source: MGI
    3. blastocyst development Source: MGI
    4. bone resorption Source: MGI
    5. cholesterol metabolic process Source: MGI
    6. chromatin remodeling Source: UniProtKB
    7. embryonic limb morphogenesis Source: MGI
    8. endocrine pancreas development Source: MGI
    9. fatty acid biosynthetic process Source: MGI
    10. fatty acid transport Source: MGI
    11. glucose homeostasis Source: UniProtKB
    12. glucose import Source: UniProtKB
    13. heme biosynthetic process Source: MGI
    14. insulin secretion Source: MGI
    15. liver development Source: MGI
    16. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    17. paraxial mesoderm formation Source: MGI
    18. placenta development Source: MGI
    19. positive regulation of transcription, DNA-templated Source: UniProtKB
    20. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    21. protein localization Source: MGI
    22. regulation of hormone secretion Source: MGI
    23. regulation of insulin secretion Source: MGI
    24. regulation of transcription, DNA-templated Source: MGI
    25. regulation of transcription from RNA polymerase II promoter Source: MGI
    26. regulation of Wnt signaling pathway Source: MGI
    27. renal glucose absorption Source: UniProtKB
    28. reproductive structure development Source: MGI
    29. response to glucose Source: MGI
    30. response to oxidative stress Source: MGI
    31. reverse cholesterol transport Source: MGI
    32. SMAD protein signal transduction Source: MGI

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_214529. Regulation of gene expression in beta cells.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hepatocyte nuclear factor 1-alpha
    Short name:
    HNF-1-alpha
    Short name:
    HNF-1A
    Alternative name(s):
    Liver-specific transcription factor LF-B1
    Short name:
    LFB1
    Transcription factor 1
    Short name:
    TCF-1
    Gene namesi
    Name:Hnf1a
    Synonyms:Hnf-1, Hnf-1a, Tcf1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:98504. Hnf1a.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. nucleus Source: UniProtKB
    3. photoreceptor outer segment Source: MGI
    4. pronucleus Source: MGI
    5. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice are born at less than half of the expected frequency. Neonates are slightly smaller than normal and do not grow normally. After 5 weeks mice weigh only 50 to 60% as much as their littermates. Mice develop non-insulin-dependent diabetes mellitus (NIDDM) 2 weeks after birth. Mice exhibit elevated levels of blood glucose, combined with reduced blood levels of insulin and insulin-like growth factor I (IGFI). Males and females are sterile.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 628628Hepatocyte nuclear factor 1-alphaPRO_0000049116Add
    BLAST

    Proteomic databases

    MaxQBiP22361.
    PaxDbiP22361.
    PRIDEiP22361.

    PTM databases

    PhosphoSiteiP22361.

    Expressioni

    Tissue specificityi

    Liver.

    Gene expression databases

    ArrayExpressiP22361.
    BgeeiP22361.
    CleanExiMM_HNF1A.
    GenevestigatoriP22361.

    Interactioni

    Subunit structurei

    Binds DNA as a dimer. Interacts with PCBD1. Heterotetramer with PCBD1; formed by a dimer of dimers.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Sirt1Q923E45EBI-5272860,EBI-1802585

    Protein-protein interaction databases

    BioGridi203999. 8 interactions.
    IntActiP22361. 2 interactions.
    MINTiMINT-4097610.
    STRINGi10090.ENSMUSP00000031535.

    Structurei

    Secondary structure

    1
    628
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi4 – 1815
    Helixi23 – 308

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1F93X-ray2.60E/F/G/H1-32[»]
    1G2YX-ray1.00A/B/C/D1-32[»]
    1G2ZX-ray1.15A/B1-32[»]
    1G39X-ray1.22A/B/C/D1-32[»]
    1JB6X-ray1.70A/B1-33[»]
    ProteinModelPortaliP22361.
    SMRiP22361. Positions 2-31, 85-286.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22361.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 3131DimerizationAdd
    BLAST
    Regioni130 – 1323Interaction with DNABy similarity
    Regioni143 – 1497Interaction with DNABy similarity
    Regioni155 – 1584Interaction with DNABy similarity
    Regioni203 – 2064Interaction with DNABy similarity
    Regioni263 – 2653Interaction with DNABy similarity
    Regioni270 – 2734Interaction with DNABy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi197 – 2059Nuclear localization signalSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi71 – 8010Asp/Glu-rich (acidic; potential involvement with transcription)

    Sequence similaritiesi

    Belongs to the HNF1 homeobox family.Curated
    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG79356.
    GeneTreeiENSGT00730000110937.
    HOGENOMiHOG000015305.
    HOVERGENiHBG005980.
    InParanoidiP22361.
    KOiK08036.
    OMAiSHVAQSP.
    OrthoDBiEOG769ZJ9.
    TreeFamiTF320327.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    1.10.260.40. 1 hit.
    InterProiIPR006899. HNF-1_N.
    IPR023219. HNF1_dimer_dom.
    IPR006898. HNF1a_C.
    IPR006897. HNF1b_C.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    IPR010982. Lambda_DNA-bd_dom.
    [Graphical view]
    PfamiPF04814. HNF-1_N. 1 hit.
    PF04813. HNF-1A_C. 1 hit.
    PF04812. HNF-1B_C. 1 hit.
    PF00046. Homeobox. 1 hit.
    [Graphical view]
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF100957. SSF100957. 1 hit.
    SSF46689. SSF46689. 1 hit.
    SSF47413. SSF47413. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P22361-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVSKLSQLQT ELLAALLESG LSKEALIQAL GEPGPYLMVG EGPLDKGESC    50
    GGSRGDLTEL PNGLGETRGS EDDTDDDGED FAPPILKELE NLSPEEAAHQ 100
    KAVVESLLQE DPWRVAKMVK SYLQQHNIPQ REVVDTTGLN QSHLSQHLNK 150
    GTPMKTQKRA ALYTWYVRKQ REVAQQFTHA GQGGLIEEPT GDELPTKKGR 200
    RNRFKWGPAS QQILFQAYER QKNPSKEERE TLVEECNRAE CIQRGVSPSQ 250
    AQGLGSNLVT EVRVYNWFAN RRKEEAFRHK LAMDTYNGPP PGPGPGPALP 300
    AHSSPGLPTT TLSPSKVHGV RYGQSATSEA AEVPSSSGGP LVTVSAALHQ 350
    VSPTGLEPSS LLSTEAKLVS ATGGPLPPVS TLTALHSLEQ TSPGLNQQPQ 400
    NLIMASLPGV MTIGPGEPAS LGPTFTNTGA STLVIGLAST QAQSVPVINS 450
    MGSSLTTLQP VQFSQPLHPS YQQPLMPPVQ SHVAQSPFMA TMAQLQSPHA 500
    LYSHKPEVAQ YTHTSLLPQT MLITDTNLST LASLTPTKQV FTSDTEASSE 550
    PGLHEPPSPA TTIHIPSQDP SNIQHLQPAH RLSTSPTVSS SSLVLYQSSD 600
    SNGHSHLLPS NHSVIETFIS TQMASSSQ 628
    Length:628
    Mass (Da):67,253
    Last modified:July 27, 2011 - v2
    Checksum:i737920D47BA1F081
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti89 – 891L → P in AAA37821. (PubMed:2263635)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M57966 mRNA. Translation: AAA37821.1.
    AC116500 Genomic DNA. No translation available.
    CCDSiCCDS19577.1.
    PIRiA39262.
    RefSeqiNP_033353.2. NM_009327.3.
    UniGeneiMm.332607.

    Genome annotation databases

    EnsembliENSMUST00000031535; ENSMUSP00000031535; ENSMUSG00000029556.
    GeneIDi21405.
    KEGGimmu:21405.
    UCSCiuc008zcz.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M57966 mRNA. Translation: AAA37821.1 .
    AC116500 Genomic DNA. No translation available.
    CCDSi CCDS19577.1.
    PIRi A39262.
    RefSeqi NP_033353.2. NM_009327.3.
    UniGenei Mm.332607.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1F93 X-ray 2.60 E/F/G/H 1-32 [» ]
    1G2Y X-ray 1.00 A/B/C/D 1-32 [» ]
    1G2Z X-ray 1.15 A/B 1-32 [» ]
    1G39 X-ray 1.22 A/B/C/D 1-32 [» ]
    1JB6 X-ray 1.70 A/B 1-33 [» ]
    ProteinModelPortali P22361.
    SMRi P22361. Positions 2-31, 85-286.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 203999. 8 interactions.
    IntActi P22361. 2 interactions.
    MINTi MINT-4097610.
    STRINGi 10090.ENSMUSP00000031535.

    PTM databases

    PhosphoSitei P22361.

    Proteomic databases

    MaxQBi P22361.
    PaxDbi P22361.
    PRIDEi P22361.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000031535 ; ENSMUSP00000031535 ; ENSMUSG00000029556 .
    GeneIDi 21405.
    KEGGi mmu:21405.
    UCSCi uc008zcz.2. mouse.

    Organism-specific databases

    CTDi 6927.
    MGIi MGI:98504. Hnf1a.

    Phylogenomic databases

    eggNOGi NOG79356.
    GeneTreei ENSGT00730000110937.
    HOGENOMi HOG000015305.
    HOVERGENi HBG005980.
    InParanoidi P22361.
    KOi K08036.
    OMAi SHVAQSP.
    OrthoDBi EOG769ZJ9.
    TreeFami TF320327.

    Enzyme and pathway databases

    Reactomei REACT_214529. Regulation of gene expression in beta cells.

    Miscellaneous databases

    EvolutionaryTracei P22361.
    NextBioi 300672.
    PROi P22361.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P22361.
    Bgeei P22361.
    CleanExi MM_HNF1A.
    Genevestigatori P22361.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    1.10.260.40. 1 hit.
    InterProi IPR006899. HNF-1_N.
    IPR023219. HNF1_dimer_dom.
    IPR006898. HNF1a_C.
    IPR006897. HNF1b_C.
    IPR001356. Homeobox_dom.
    IPR009057. Homeodomain-like.
    IPR010982. Lambda_DNA-bd_dom.
    [Graphical view ]
    Pfami PF04814. HNF-1_N. 1 hit.
    PF04813. HNF-1A_C. 1 hit.
    PF04812. HNF-1B_C. 1 hit.
    PF00046. Homeobox. 1 hit.
    [Graphical view ]
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF100957. SSF100957. 1 hit.
    SSF46689. SSF46689. 1 hit.
    SSF47413. SSF47413. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1."
      Kuo C.J., Conley P.B., Hsieh C.L., Francke U., Crabtree G.R.
      Proc. Natl. Acad. Sci. U.S.A. 87:9838-9842(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "Structure of the gene encoding hepatocyte nuclear factor 1 (HNF1)."
      Bach I., Pontoglio M., Yaniv M.
      Nucleic Acids Res. 20:4199-4204(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: GENE STRUCTURE.
    4. "Laron dwarfism and non-insulin-dependent diabetes mellitus in the Hnf-1alpha knockout mouse."
      Lee Y.H., Sauer B., Gonzalez F.J.
      Mol. Cell. Biol. 18:3059-3068(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    5. "Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis."
      Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.
      J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    6. "Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver."
      Servitja J.M., Pignatelli M., Maestro M.A., Cardalda C., Boj S.F., Lozano J., Blanco E., Lafuente A., McCarthy M.I., Sumoy L., Guigo R., Ferrer J.
      Mol. Cell. Biol. 29:2945-2959(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "High-resolution structure of the HNF-1alpha dimerization domain."
      Rose R.B., Endrizzi J.A., Cronk J.D., Holton J., Alber T.
      Biochemistry 39:15062-15070(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1-32, SUBUNIT.
    8. "Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha."
      Rose R.B., Bayle J.H., Endrizzi J.A., Cronk J.D., Crabtree G.R., Alber T.
      Nat. Struct. Biol. 7:744-748(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-32 IN COMPLEX WITH PCBD1, SUBUNIT, FUNCTION.
    9. "The dimerization domain of HNF-1alpha: structure and plasticity of an intertwined four-helix bundle with application to diabetes mellitus."
      Narayana N., Hua Q., Weiss M.A.
      J. Mol. Biol. 310:635-658(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2-32, SUBUNIT.

    Entry informationi

    Entry nameiHNF1A_MOUSE
    AccessioniPrimary (citable) accession number: P22361
    Secondary accession number(s): E9QP86
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1991
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 149 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

    3D-structure, Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3