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Protein

Pancreas/duodenum homeobox protein 1

Gene

Pdx1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Biological processi

  • cell differentiation Source: MGI
  • central nervous system development Source: Ensembl
  • detection of glucose Source: Ensembl
  • digestive tract development Source: MGI
  • endocrine pancreas development Source: MGI
  • exocrine pancreas development Source: MGI
  • glucose homeostasis Source: MGI
  • glucose metabolic process Source: MGI
  • insulin secretion Source: MGI
  • liver development Source: MGI
  • morphogenesis of embryonic epithelium Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • negative regulation of type B pancreatic cell apoptotic process Source: MGI
  • nitric oxide mediated signal transduction Source: MGI
  • organ regeneration Source: Ensembl
  • organ senescence Source: Ensembl
  • pancreas development Source: MGI
  • positive regulation of cell death Source: Ensembl
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of DNA binding Source: Ensembl
  • positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • regulation of cell proliferation Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • response to chlorate Source: Ensembl
  • response to cytokine Source: Ensembl
  • response to drug Source: Ensembl
  • response to fatty acid Source: Ensembl
  • response to glucocorticoid Source: Ensembl
  • response to iron(II) ion Source: Ensembl
  • response to leucine Source: Ensembl
  • response to nicotine Source: Ensembl
  • response to vitamin Source: Ensembl
  • response to wounding Source: Ensembl
  • smoothened signaling pathway Source: Ensembl
  • stem cell differentiation Source: Ensembl
  • transdifferentiation Source: Ensembl
  • type B pancreatic cell differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_296789. Regulation of gene expression in early pancreatic precursor cells.
REACT_322034. 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 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:102851. Pdx1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • intracellular Source: MGI
  • nuclear speck Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
Complete GO annotation...

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

BgeeiP52946.
CleanExiMM_PDX1.
ExpressionAtlasiP52946. differential.
GenevisibleiP52946. MM.

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.
STRINGi10090.ENSMUSP00000082729.

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.
GeneTreeiENSGT00760000118940.
HOGENOMiHOG000115484.
HOVERGENiHBG004525.
InParanoidiP52946.
KOiK07594.
OMAiPPPCLYM.
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

        10         20         30         40         50
MNSEEQYYAA TQLYKDPCAF QRGPVPEFSA NPPACLYMGR QPPPPPPPQF
60 70 80 90 100
TSSLGSLEQG SPPDISPYEV PPLASDDPAG AHLHHHLPAQ LGLAHPPPGP
110 120 130 140 150
FPNGTEPGGL EEPNRVQLPF PWMKSTKAHA WKGQWAGGAY TAEPEENKRT
160 170 180 190 200
RTAYTRAQLL ELEKEFLFNK YISRPRRVEL AVMLNLTERH IKIWFQNRRM
210 220 230 240 250
KWKKEEDKKR SSGTPSGGGG GEEPEQDCAV TSGEELLAVP PLPPPGGAVP
260 270 280
PGVPAAVREG LLPSGLSVSP QPSSIAPLRP QEPR
Length:284
Mass (Da):30,999
Last modified:October 1, 1996 - v1
Checksum:iA57D04569D14E3C4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi202101. 4 interactions.
IntActiP52946. 2 interactions.
MINTiMINT-3982089.
STRINGi10090.ENSMUSP00000082729.

PTM databases

PhosphoSiteiP52946.

Proteomic databases

PRIDEiP52946.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3651.
MGIiMGI:102851. Pdx1.

Phylogenomic databases

eggNOGiNOG271681.
GeneTreeiENSGT00760000118940.
HOGENOMiHOG000115484.
HOVERGENiHBG004525.
InParanoidiP52946.
KOiK07594.
OMAiPPPCLYM.
OrthoDBiEOG744TB4.
PhylomeDBiP52946.
TreeFamiTF326223.

Enzyme and pathway databases

ReactomeiREACT_296789. Regulation of gene expression in early pancreatic precursor cells.
REACT_322034. Regulation of gene expression in beta cells.

Miscellaneous databases

NextBioi294534.
PROiP52946.
SOURCEiSearch...

Gene expression databases

BgeeiP52946.
CleanExiMM_PDX1.
ExpressionAtlasiP52946. differential.
GenevisibleiP52946. MM.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 141 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

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 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.