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P52946 (PDX1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Pdx1
Synonyms:Ipf1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length284 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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'. Ref.4 Ref.5

Subunit structure

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. Ref.4 Ref.5 Ref.6

Subcellular location

Nucleus. Cytoplasmcytosol Ref.7.

Tissue specificity

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

Developmental stage

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.

Domain

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.

Post-translational modification

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. Ref.7 Ref.8

Sequence similarities

Belongs to the Antp homeobox family. IPF1/XlHbox-8 subfamily.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DiseaseDiabetes mellitus
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from mutant phenotype PubMed 16418487. Source: MGI

central nervous system development

Inferred from electronic annotation. Source: Ensembl

detection of glucose

Inferred from electronic annotation. Source: Ensembl

digestive tract development

Inferred from mutant phenotype PubMed 19619492. Source: MGI

endocrine pancreas development

Inferred from mutant phenotype PubMed 18155690. Source: MGI

exocrine pancreas development

Inferred from mutant phenotype PubMed 16126192. Source: MGI

glucose homeostasis

Inferred from mutant phenotype PubMed 18155690. Source: MGI

glucose metabolic process

Inferred from direct assay PubMed 12904469. Source: MGI

insulin secretion

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from mutant phenotype PubMed 19619492. Source: MGI

morphogenesis of embryonic epithelium

Inferred from mutant phenotype PubMed 8625829. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 18155690. Source: MGI

negative regulation of intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Inferred from mutant phenotype PubMed 20811152. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17056599. Source: MGI

negative regulation of type B pancreatic cell apoptotic process

Inferred from mutant phenotype PubMed 20811152. Source: MGI

nitric oxide mediated signal transduction

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from electronic annotation. Source: Ensembl

organ senescence

Inferred from electronic annotation. Source: Ensembl

pancreas development

Inferred from mutant phenotype PubMed 16418487PubMed 8625829. Source: MGI

positive regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell death

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 18155690. Source: MGI

positive regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 14701942PubMed 15486225. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12368292. Source: MGI

regulation of cell proliferation

Inferred from direct assay PubMed 12488434. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 14701942. Source: MGI

response to chlorate

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to fatty acid

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to iron(II) ion

Inferred from electronic annotation. Source: Ensembl

response to leucine

Inferred from electronic annotation. Source: Ensembl

response to nicotine

Inferred from electronic annotation. Source: Ensembl

response to vitamin

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from electronic annotation. Source: Ensembl

smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

stem cell differentiation

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

transdifferentiation

Inferred from electronic annotation. Source: Ensembl

type B pancreatic cell differentiation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

intracellular

Inferred from direct assay PubMed 10868931PubMed 15793245. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 12488434PubMed 14702043PubMed 15486225PubMed 15888377PubMed 18155690. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 12368292PubMed 12972592PubMed 15486225PubMed 17056599. Source: MGI

chromatin binding

Inferred from direct assay PubMed 19651901. Source: MGI

core promoter sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 17126328PubMed 21399612. Source: IntAct

sequence-specific DNA binding

Inferred from direct assay PubMed 14701942. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 15486225. Source: MGI

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 284284Pancreas/duodenum homeobox protein 1
PRO_0000049149

Regions

DNA binding147 – 20660Homeobox
Region13 – 7361Transactivation domain By similarity
Motif119 – 1246Antp-type hexapeptide
Motif198 – 2047Nuclear localization signal
Compositional bias42 – 487Poly-Pro
Compositional bias217 – 2215Poly-Gly

Amino acid modifications

Modified residue1521Phosphothreonine; by PASK Ref.7
Modified residue2691Phosphoserine; by HIPK2 Ref.8

Experimental info

Mutagenesis1521T → D or E: Displays a more cytosolic distribution. Ref.7
Mutagenesis2691S → A: Reduced phosphorylation by HIPK2. Ref.8
Mutagenesis2691S → E: Abnormal subnuclear localization upon glucose accumulation. Ref.8

Sequences

Sequence LengthMass (Da)Tools
P52946 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: A57D04569D14E3C4

FASTA28430,999
        10         20         30         40         50         60 
MNSEEQYYAA TQLYKDPCAF QRGPVPEFSA NPPACLYMGR QPPPPPPPQF TSSLGSLEQG 

        70         80         90        100        110        120 
SPPDISPYEV PPLASDDPAG AHLHHHLPAQ LGLAHPPPGP FPNGTEPGGL EEPNRVQLPF 

       130        140        150        160        170        180 
PWMKSTKAHA WKGQWAGGAY TAEPEENKRT RTAYTRAQLL ELEKEFLFNK YISRPRRVEL 

       190        200        210        220        230        240 
AVMLNLTERH IKIWFQNRRM KWKKEEDKKR SSGTPSGGGG GEEPEQDCAV TSGEELLAVP 

       250        260        270        280 
PLPPPGGAVP PGVPAAVREG LLPSGLSVSP QPSSIAPLRP QEPR 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS39398.1.
PIRS39581.
RefSeqNP_032840.1. NM_008814.3.
UniGeneMm.389714.

3D structure databases

ProteinModelPortalP52946.
SMRP52946. Positions 147-206.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202101. 4 interactions.
IntActP52946. 2 interactions.
MINTMINT-3982089.

PTM databases

PhosphoSiteP52946.

Proteomic databases

PRIDEP52946.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000085591; ENSMUSP00000082729; ENSMUSG00000029644.
GeneID18609.
KEGGmmu:18609.
UCSCuc009any.2. mouse.

Organism-specific databases

CTD3651.
MGIMGI:102851. Pdx1.

Phylogenomic databases

eggNOGNOG271681.
GeneTreeENSGT00750000117486.
HOGENOMHOG000115484.
HOVERGENHBG004525.
InParanoidQ3ZB03.
KOK07594.
OMACLYMSRQ.
OrthoDBEOG744TB4.
PhylomeDBP52946.
TreeFamTF326223.

Enzyme and pathway databases

ReactomeREACT_13641. Regulation of Beta-Cell Development.
REACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressP52946.
BgeeP52946.
CleanExMM_PDX1.
GenevestigatorP52946.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017995. Homeobox_antennapedia.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSPR00025. ANTENNAPEDIA.
PR00024. HOMEOBOX.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294534.
PROP52946.
SOURCESearch...

Entry information

Entry namePDX1_MOUSE
AccessionPrimary (citable) accession number: P52946
Secondary accession number(s): Q3ZB03
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot