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P52946

- PDX1_MOUSE

UniProt

P52946 - PDX1_MOUSE

Protein

Pancreas/duodenum homeobox protein 1

Gene

Pdx1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    Functioni

    Activates insulin and somatostatin gene transcription. Key regulator of islet peptide hormone expression but also responsible for the development of the pancreas, most probably by determining maturation and differentiation of common pancreatic precursor cells in the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3'.2 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi147 – 20660HomeoboxPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin binding Source: MGI
    2. core promoter sequence-specific DNA binding Source: Ensembl
    3. DNA binding Source: MGI
    4. protein binding Source: IntAct
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    7. sequence-specific DNA binding Source: MGI
    8. sequence-specific DNA binding transcription factor activity Source: MGI

    GO - Biological processi

    1. cell differentiation Source: MGI
    2. central nervous system development Source: Ensembl
    3. detection of glucose Source: Ensembl
    4. digestive tract development Source: MGI
    5. endocrine pancreas development Source: MGI
    6. exocrine pancreas development Source: MGI
    7. glucose homeostasis Source: MGI
    8. glucose metabolic process Source: MGI
    9. insulin secretion Source: Ensembl
    10. liver development Source: MGI
    11. morphogenesis of embryonic epithelium Source: MGI
    12. negative regulation of cell proliferation Source: MGI
    13. negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: MGI
    14. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    15. negative regulation of type B pancreatic cell apoptotic process Source: MGI
    16. nitric oxide mediated signal transduction Source: Ensembl
    17. organ regeneration Source: Ensembl
    18. organ senescence Source: Ensembl
    19. pancreas development Source: MGI
    20. positive regulation of cell death Source: Ensembl
    21. positive regulation of cell proliferation Source: MGI
    22. positive regulation of DNA binding Source: Ensembl
    23. positive regulation of insulin secretion Source: Ensembl
    24. positive regulation of transcription, DNA-templated Source: MGI
    25. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
    26. regulation of cell proliferation Source: MGI
    27. regulation of transcription from RNA polymerase II promoter Source: MGI
    28. response to chlorate Source: Ensembl
    29. response to cytokine Source: Ensembl
    30. response to drug Source: Ensembl
    31. response to fatty acid Source: Ensembl
    32. response to glucocorticoid Source: Ensembl
    33. response to iron(II) ion Source: Ensembl
    34. response to leucine Source: Ensembl
    35. response to nicotine Source: Ensembl
    36. response to vitamin Source: Ensembl
    37. response to wounding Source: Ensembl
    38. smoothened signaling pathway Source: Ensembl
    39. stem cell differentiation Source: Ensembl
    40. transdifferentiation Source: Ensembl
    41. type B pancreatic cell differentiation Source: Ensembl

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_208465. Regulation of gene expression in early pancreatic precursor cells.
    REACT_214529. Regulation of gene expression in beta cells.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pancreas/duodenum homeobox protein 1
    Alternative name(s):
    Insulin promoter factor 1
    Short name:
    IPF-1
    Islet/duodenum homeobox 1
    Short name:
    IDX-1
    Somatostatin-transactivating factor 1
    Short name:
    STF-1
    Gene namesi
    Name:Pdx1
    Synonyms:Ipf1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:102851. Pdx1.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation. Cytoplasmcytosol 1 Publication

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. intracellular Source: MGI
    3. nucleoplasm Source: Reactome
    4. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi152 – 1521T → D or E: Displays a more cytosolic distribution. 1 Publication
    Mutagenesisi269 – 2691S → A: Reduced phosphorylation by HIPK2. 1 Publication
    Mutagenesisi269 – 2691S → E: Abnormal subnuclear localization upon glucose accumulation. 1 Publication

    Keywords - Diseasei

    Diabetes mellitus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 284284Pancreas/duodenum homeobox protein 1PRO_0000049149Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei152 – 1521Phosphothreonine; by PASK1 Publication
    Modified residuei269 – 2691Phosphoserine; by HIPK21 Publication

    Post-translational modificationi

    Phosphorylated by the SAPK2 pathway at high intracellular glucose concentration. Phosphorylated by HIPK2 on Ser-269 upon glucose accumulation. This phoyphorylation mediates subnuclear localization shifting. Phosphorylation by PASK may lead to translocation into the cytosol.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiP52946.

    PTM databases

    PhosphoSiteiP52946.

    Expressioni

    Tissue specificityi

    Duodenum and pancreas (Langerhans islet beta cells and small subsets of endocrine non-beta-cells, at low levels in acinar cells).

    Developmental stagei

    At 8.5 dpc, detected in the gut epithelium from which the pancreatic buds are formed. Transient expression in pancreatic ducts, endocrine and acinar cells. Down-regulated around 10.5 dpc when expression becomes restricted to differentiated beta-cells.

    Gene expression databases

    ArrayExpressiP52946.
    BgeeiP52946.
    CleanExiMM_PDX1.
    GenevestigatoriP52946.

    Interactioni

    Subunit structurei

    Interacts with the basic helix-loop-helix domains of TCF3(E47) and NEUROD1 and with HMG-I(Y). Interacts with the methyltransferase SETD7 By similarity. Interacts with SPOP. Part of a PDX1:PBX1b:MEIS2b complex.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Rb1P134052EBI-7128945,EBI-971782
    SpopQ6ZWS85EBI-7128945,EBI-7128920

    Protein-protein interaction databases

    BioGridi202101. 4 interactions.
    IntActiP52946. 2 interactions.
    MINTiMINT-3982089.

    Structurei

    3D structure databases

    ProteinModelPortaliP52946.
    SMRiP52946. Positions 147-206.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni13 – 7361Transactivation domainBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi119 – 1246Antp-type hexapeptide
    Motifi198 – 2047Nuclear localization signal

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi42 – 487Poly-Pro
    Compositional biasi217 – 2215Poly-Gly

    Domaini

    The Antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter.By similarity
    The homeodomain, which contains the nuclear localization signal, not only mediates DNA-binding, but also acts as a protein-protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y).By similarity

    Sequence similaritiesi

    Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Homeobox

    Phylogenomic databases

    eggNOGiNOG271681.
    GeneTreeiENSGT00750000117486.
    HOGENOMiHOG000115484.
    HOVERGENiHBG004525.
    InParanoidiQ3ZB03.
    KOiK07594.
    OMAiCLYMSRQ.
    OrthoDBiEOG744TB4.
    PhylomeDBiP52946.
    TreeFamiTF326223.

    Family and domain databases

    Gene3Di1.10.10.60. 1 hit.
    InterProiIPR017995. Homeobox_antennapedia.
    IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR020479. Homeobox_metazoa.
    IPR009057. Homeodomain-like.
    [Graphical view]
    PfamiPF00046. Homeobox. 1 hit.
    [Graphical view]
    PRINTSiPR00025. ANTENNAPEDIA.
    PR00024. HOMEOBOX.
    SMARTiSM00389. HOX. 1 hit.
    [Graphical view]
    SUPFAMiSSF46689. SSF46689. 1 hit.
    PROSITEiPS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P52946-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNSEEQYYAA TQLYKDPCAF QRGPVPEFSA NPPACLYMGR QPPPPPPPQF    50
    TSSLGSLEQG SPPDISPYEV PPLASDDPAG AHLHHHLPAQ LGLAHPPPGP 100
    FPNGTEPGGL EEPNRVQLPF PWMKSTKAHA WKGQWAGGAY TAEPEENKRT 150
    RTAYTRAQLL ELEKEFLFNK YISRPRRVEL AVMLNLTERH IKIWFQNRRM 200
    KWKKEEDKKR SSGTPSGGGG GEEPEQDCAV TSGEELLAVP PLPPPGGAVP 250
    PGVPAAVREG LLPSGLSVSP QPSSIAPLRP QEPR 284
    Length:284
    Mass (Da):30,999
    Last modified:October 1, 1996 - v1
    Checksum:iA57D04569D14E3C4
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X74342 mRNA. Translation: CAA52389.1.
    AK020261 mRNA. Translation: BAB32045.1.
    BC103572 mRNA. Translation: AAI03573.1.
    BC103581 mRNA. Translation: AAI03582.1.
    BC103582 mRNA. Translation: AAI03583.1.
    BC105642 mRNA. Translation: AAI05643.1.
    CCDSiCCDS39398.1.
    PIRiS39581.
    RefSeqiNP_032840.1. NM_008814.3.
    UniGeneiMm.389714.

    Genome annotation databases

    EnsembliENSMUST00000085591; ENSMUSP00000082729; ENSMUSG00000029644.
    GeneIDi18609.
    KEGGimmu:18609.
    UCSCiuc009any.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X74342 mRNA. Translation: CAA52389.1 .
    AK020261 mRNA. Translation: BAB32045.1 .
    BC103572 mRNA. Translation: AAI03573.1 .
    BC103581 mRNA. Translation: AAI03582.1 .
    BC103582 mRNA. Translation: AAI03583.1 .
    BC105642 mRNA. Translation: AAI05643.1 .
    CCDSi CCDS39398.1.
    PIRi S39581.
    RefSeqi NP_032840.1. NM_008814.3.
    UniGenei Mm.389714.

    3D structure databases

    ProteinModelPortali P52946.
    SMRi P52946. Positions 147-206.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202101. 4 interactions.
    IntActi P52946. 2 interactions.
    MINTi MINT-3982089.

    PTM databases

    PhosphoSitei P52946.

    Proteomic databases

    PRIDEi P52946.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000085591 ; ENSMUSP00000082729 ; ENSMUSG00000029644 .
    GeneIDi 18609.
    KEGGi mmu:18609.
    UCSCi uc009any.2. mouse.

    Organism-specific databases

    CTDi 3651.
    MGIi MGI:102851. Pdx1.

    Phylogenomic databases

    eggNOGi NOG271681.
    GeneTreei ENSGT00750000117486.
    HOGENOMi HOG000115484.
    HOVERGENi HBG004525.
    InParanoidi Q3ZB03.
    KOi K07594.
    OMAi CLYMSRQ.
    OrthoDBi EOG744TB4.
    PhylomeDBi P52946.
    TreeFami TF326223.

    Enzyme and pathway databases

    Reactomei REACT_208465. Regulation of gene expression in early pancreatic precursor cells.
    REACT_214529. Regulation of gene expression in beta cells.

    Miscellaneous databases

    NextBioi 294534.
    PROi P52946.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P52946.
    Bgeei P52946.
    CleanExi MM_PDX1.
    Genevestigatori P52946.

    Family and domain databases

    Gene3Di 1.10.10.60. 1 hit.
    InterProi IPR017995. Homeobox_antennapedia.
    IPR017970. Homeobox_CS.
    IPR001356. Homeobox_dom.
    IPR020479. Homeobox_metazoa.
    IPR009057. Homeodomain-like.
    [Graphical view ]
    Pfami PF00046. Homeobox. 1 hit.
    [Graphical view ]
    PRINTSi PR00025. ANTENNAPEDIA.
    PR00024. HOMEOBOX.
    SMARTi SM00389. HOX. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46689. SSF46689. 1 hit.
    PROSITEi PS00027. HOMEOBOX_1. 1 hit.
    PS50071. HOMEOBOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "IPF1, a homeodomain-containing transactivator of the insulin gene."
      Ohlsson H., Karlsson K., Edlund T.
      EMBO J. 12:4251-4259(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "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: Cecum.
    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].
    4. "An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2)."
      Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S., Buchberg A.M., Wright C.V., MacDonald R.J.
      Mol. Cell. Biol. 18:5109-5120(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
    5. "DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex."
      Liu Y., MacDonald R.J., Swift G.H.
      J. Biol. Chem. 276:17985-17993(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH MEIS2 AND PBX1.
    6. "Identification of PCIF1, a POZ domain protein that inhibits PDX-1 (MODY4) transcriptional activity."
      Liu A., Desai B.M., Stoffers D.A.
      Mol. Cell. Biol. 24:4372-4383(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SPOP.
      Strain: BALB/c.
      Tissue: Pancreas.
    7. "Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 nuclear import in pancreatic beta-cells."
      An R., da Silva Xavier G., Hao H.X., Semplici F., Rutter J., Rutter G.A.
      Biochem. Soc. Trans. 34:791-793(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-152, MUTAGENESIS OF THR-152.
    8. "Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization."
      An R., da Silva Xavier G., Semplici F., Vakhshouri S., Hao H.X., Rutter J., Pagano M.A., Meggio F., Pinna L.A., Rutter G.A.
      Biochem. Biophys. Res. Commun. 399:155-161(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-269 BY HIPK2, MUTAGENESIS OF SER-269.

    Entry informationi

    Entry nameiPDX1_MOUSE
    AccessioniPrimary (citable) accession number: P52946
    Secondary accession number(s): Q3ZB03
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 135 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, 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