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P52945 (PDX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pancreas/duodenum homeobox protein 1

Short name=PDX-1
Alternative name(s):
Glucose-sensitive factor
Short name=GSF
Insulin promoter factor 1
Short name=IPF-1
Insulin upstream factor 1
Short name=IUF-1
Islet/duodenum homeobox-1
Short name=IDX-1
Somatostatin-transactivating factor 1
Short name=STF-1
Gene names
Name:PDX1
Synonyms:IPF1, STF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length283 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Activates insulin, somatostatin, glucokinase, islet amyloid polypeptide and glucose transporter type 2 gene transcription. Particularly involved in glucose-dependent regulation of insulin gene transcription. 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 preferentially the DNA motif 5'-[CT]TAAT[TG]-3'. During development, specifies the early pancreatic epithelium, permitting its proliferation, branching and subsequent differentiation. At adult stage, required for maintaining the hormone-producing phenotype of the beta-cell.

Subunit structure

Interacts with the basic helix-loop-helix domains of TCF3(E47) and NEUROD1 and with HMG-I(Y). Interacts with SPOP By similarity. Interacts with the methyltransferase SETD7. Part of a PDX1:PBX1b:MEIS2b complex. Ref.10

Subcellular location

Nucleus. Cytoplasmcytosol By similarity.

Tissue specificity

Duodenum and pancreas (Langerhans islet beta cells and small subsets of endocrine non-beta-cells, at low levels in acinar 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-268 upon glucose accumulation. This phoyphorylation mediates subnuclear localization shifting. Phosphorylation by PASK may lead to translocation into the cytosol By similarity. Ref.11

Involvement in disease

Pancreatic agenesis, congenital (PAGEN) [MIM:260370]: Autosomal recessive disorder is characterized by absence or hypoplasia of pancreas, leading to early-onset insulin-dependent diabetes mellitus. This was found in a frameshift mutation that produces a truncated protein and results in a second initiation that produces a second protein that act as a dominant negative mutant.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Maturity-onset diabetes of the young 4 (MODY4) [MIM:606392]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13

Miscellaneous

According to Ref.10, it may be methylated by SETD7 in vitro. However, the relevance of methylation is unsure in vivo.

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
   Coding sequence diversityPolymorphism
   DiseaseDiabetes mellitus
Disease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcentral nervous system development

Inferred from electronic annotation. Source: Ensembl

detection of glucose

Inferred from sequence or structural similarity. Source: BHF-UCL

digestive tract development

Inferred from electronic annotation. Source: Ensembl

endocrine pancreas development

Traceable author statement. Source: Reactome

exocrine pancreas development

Inferred from electronic annotation. Source: Ensembl

generation of precursor metabolites and energy

Traceable author statement PubMed 8954967. Source: ProtInc

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

insulin secretion

Inferred from direct assay PubMed 17941991. Source: BHF-UCL

liver development

Inferred from electronic annotation. Source: Ensembl

morphogenesis of embryonic epithelium

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

nitric oxide mediated signal transduction

Inferred from direct assay PubMed 17941991. Source: BHF-UCL

organ morphogenesis

Traceable author statement Ref.9. Source: ProtInc

organ regeneration

Inferred from electronic annotation. Source: Ensembl

organ senescence

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

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

Traceable author statement PubMed 8954967. Source: ProtInc

transdifferentiation

Inferred from electronic annotation. Source: Ensembl

type B pancreatic cell differentiation

Inferred from direct assay PubMed 12124776. Source: BHF-UCL

   Cellular_componentcytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionchromatin binding

Inferred from electronic annotation. Source: Ensembl

core promoter sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Traceable author statement PubMed 17941991. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 283283Pancreas/duodenum homeobox protein 1
PRO_0000049147

Regions

DNA binding146 – 20560Homeobox
Region13 – 7361Transactivation domain By similarity
Motif118 – 1236Antp-type hexapeptide
Motif197 – 2037Nuclear localization signal By similarity
Compositional bias42 – 5110Poly-Pro
Compositional bias216 – 2194Poly-Gly
Compositional bias239 – 2446Poly-Pro

Amino acid modifications

Modified residue1511Phosphothreonine; by PASK By similarity
Modified residue2681Phosphoserine; by HIPK2 Ref.11

Natural variations

Natural variant181C → R in MODY4. Ref.12
VAR_009309
Natural variant591Q → L in MODY4. Ref.13
VAR_009310
Natural variant761D → N in MODY4; unknown pathological significance. Ref.12 Ref.13
VAR_009311
Natural variant1971R → H in MODY4. Ref.12
VAR_009312
Natural variant2431P → PP in MODY4. Ref.13
VAR_009313

Experimental info

Sequence conflict561A → S in AAC05157. Ref.6
Sequence conflict1161Q → H in AAC05157. Ref.6
Sequence conflict210 – 2112GG → SS in AAC05157. Ref.6

Sequences

Sequence LengthMass (Da)Tools
P52945 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 5D48EC8D3289F72B

FASTA28330,771
        10         20         30         40         50         60 
MNGEEQYYAA TQLYKDPCAF QRGPAPEFSA SPPACLYMGR QPPPPPPHPF PGALGALEQG 

        70         80         90        100        110        120 
SPPDISPYEV PPLADDPAVA HLHHHLPAQL ALPHPPAGPF PEGAEPGVLE EPNRVQLPFP 

       130        140        150        160        170        180 
WMKSTKAHAW KGQWAGGAYA AEPEENKRTR TAYTRAQLLE LEKEFLFNKY ISRPRRVELA 

       190        200        210        220        230        240 
VMLNLTERHI KIWFQNRRMK WKKEEDKKRG GGTAVGGGGV AEPEQDCAVT SGEELLALPP 

       250        260        270        280 
PPPPGGAVPP AAPVAAREGR LPPGLSASPQ PSSVAPRRPQ EPR 

« Hide

References

« Hide 'large scale' references
[1]"Localization of human homeodomain transcription factor insulin promoter factor 1 (IPF1) to chromosome band 13q12.1."
Stoffel M., Stein R., Wright C.V., Espinosa R. III, le Beau M.M., Bell G.I.
Genomics 28:125-126(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene."
Inoue H., Riggs A.C., Tanizawa Y., Ueda K., Kuwano A., Liu L., Donis-Keller H., Permutt M.A.
Diabetes 45:789-794(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Pancreatic islet.
[3]Hiroshi I.
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pancreatic islet.
[4]Marshak S., Totary H., Cerasi E., Melloul D.
Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pancreatic islet.
[5]Hara M., Lindner T.H., Paz V.P., Wang X., Iwasaki N., Bell G.I.
Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"The p38/reactivating kinase mitogen-activated protein kinase cascade mediates the activation of the transcription factor insulin upstream factor 1 and insulin gene transcription by high glucose in pancreatic beta-cells."
Macfarlane W.M., Smith S.B., James R.F., Clifton A.D., Doza Y.N., Cohen P., Docherty K.
J. Biol. Chem. 272:20936-20944(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Pancreatic islet.
[7]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence."
Stoffers D.A., Zinkin N.T., Stanojevic V., Clarke W.L., Habener J.F.
Nat. Genet. 15:106-110(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PAGEN.
[10]"Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription."
Francis J., Chakrabarti S.K., Garmey J.C., Mirmira R.G.
J. Biol. Chem. 280:36244-36253(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SETD7.
[11]"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-268 BY HIPK2.
[12]"Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes."
Macfarlane W.M., Frayling T.M., Ellard S., Evans J.C., Allen L.I., Bulman M.P., Ayres S., Shepherd M., Clark P., Millward A., Demaine A., Wilkin T., Docherty K., Hattersley A.T.
J. Clin. Invest. 104:R33-R39(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY4 ARG-18; ASN-76 AND HIS-197.
[13]"Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus."
Hani E.H., Stoffers D.A., Chevre J.-C., Durand E., Stanojevic V., Dina C., Habener J.F., Froguel P.
J. Clin. Invest. 104:R41-R48(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MODY4 LEU-59; ASN-76 AND PRO-243 INS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U35632 mRNA. Translation: AAA88820.1.
S82178, S82168 Genomic DNA. Translation: AAB47101.1.
U30329 mRNA. Translation: AAA74012.1.
X99894 mRNA. Translation: CAA68169.1.
AF035260, AF035259 Genomic DNA. Translation: AAB88463.1.
AF049893 mRNA. Translation: AAC05157.1.
AL353195 Genomic DNA. Translation: CAH72544.1.
CH471075 Genomic DNA. Translation: EAX08420.1.
PIRG01926.
RefSeqNP_000200.1. NM_000209.3.
UniGeneHs.32938.

3D structure databases

ProteinModelPortalP52945.
SMRP52945. Positions 146-205.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109860. 9 interactions.
IntActP52945. 2 interactions.
MINTMINT-1894661.
STRING9606.ENSP00000370421.

PTM databases

PhosphoSiteP52945.

Polymorphism databases

DMDM1708540.

Proteomic databases

PaxDbP52945.
PRIDEP52945.

Protocols and materials databases

DNASU3651.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000381033; ENSP00000370421; ENSG00000139515.
GeneID3651.
KEGGhsa:3651.
UCSCuc001urt.2. human.

Organism-specific databases

CTD3651.
GeneCardsGC13P028494.
HGNCHGNC:6107. PDX1.
HPACAB025873.
MIM125853. phenotype.
260370. phenotype.
600733. gene.
606392. phenotype.
neXtProtNX_P52945.
Orphanet552. MODY syndrome.
2805. Partial pancreatic agenesis.
99885. Permanent neonatal diabetes mellitus.
PharmGKBPA162399173.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG271681.
HOGENOMHOG000115484.
HOVERGENHBG004525.
InParanoidP52945.
KOK07594.
OMACLYMSRQ.
OrthoDBEOG744TB4.
PhylomeDBP52945.
TreeFamTF326223.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
SignaLinkP52945.

Gene expression databases

BgeeP52945.
CleanExHS_PDX1.
GenevestigatorP52945.

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

GeneWikiPDX1.
GenomeRNAi3651.
NextBio14279.
PROP52945.
SOURCESearch...

Entry information

Entry namePDX1_HUMAN
AccessionPrimary (citable) accession number: P52945
Secondary accession number(s): O60594, Q5VYW2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM