ID:PDX1_HUMAN DESCRIPTION: RecName: Full=Pancreas/duodenum homeobox protein 1; Short=PDX-1; AltName: Full=Glucose-sensitive factor; Short=GSF; AltName: Full=Insulin promoter factor 1; Short=IPF-1; AltName: Full=Insulin upstream factor 1; Short=IUF-1; AltName: Full=Islet/duodenum homeobox-1; Short=IDX-1; AltName: Full=Somatostatin-transactivating factor 1; Short=STF-1; 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. 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: 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. SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytosol (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). DOMAIN: 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). PTM: 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). DISEASE: Defects in PDX1 are a cause of pancreatic agenesis (PAC) [MIM:260370]. This 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. DISEASE: Defects in PDX1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type 2. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. DISEASE: Defects in PDX1 are the cause of maturity-onset diabetes of the young type 4 (MODY4) [MIM:606392]; also symbolized MODY-4. MODY is 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. MISCELLANEOUS: According to PubMed:16141209, it may be methylated by SETD7 in vitro. However, the relevance of methylation is unsure in vivo. SIMILARITY: Belongs to the Antp homeobox family. IPF1/XlHbox-8 subfamily. SIMILARITY: Contains 1 homeobox DNA-binding domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PDX1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P52945
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0043565 sequence-specific DNA binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001889 liver development GO:0003309 type B pancreatic cell differentiation GO:0006006 glucose metabolic process GO:0006091 generation of precursor metabolites and energy GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0007263 nitric oxide mediated signal transduction GO:0007275 multicellular organism development GO:0008284 positive regulation of cell proliferation GO:0008285 negative regulation of cell proliferation GO:0009887 animal organ morphogenesis GO:0016331 morphogenesis of embryonic epithelium GO:0030073 insulin secretion GO:0030154 cell differentiation GO:0031016 pancreas development GO:0031017 exocrine pancreas development GO:0031018 endocrine pancreas development GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus GO:0042127 regulation of cell proliferation GO:0042593 glucose homeostasis GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048565 digestive tract development GO:0051594 detection of glucose GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:2000675 negative regulation of type B pancreatic cell apoptotic process
X99894 - H.sapiens mRNA coding for insulin promoter factor 1. JD304926 - Sequence 285950 from Patent EP1572962. U30329 - Human insulin promoter factor 1 (IPF1) mRNA, complete cds. U35632 - Human insulin promoter factor 1 (PDX-1) mRNA, complete cds. AB464648 - Synthetic construct DNA, clone: pF1KB8932, Homo sapiens PDX1 gene for pancreatic and duodenal homeobox 1, without stop codon, in Flexi system. BC111592 - Synthetic construct Homo sapiens clone IMAGE:40080548, MGC:133411 PDX1 protein (PDX1) mRNA, encodes complete protein. JD458325 - Sequence 439349 from Patent EP1572962. JD318768 - Sequence 299792 from Patent EP1572962. JD178347 - Sequence 159371 from Patent EP1572962. JD439924 - Sequence 420948 from Patent EP1572962. JD515208 - Sequence 496232 from Patent EP1572962. JD475087 - Sequence 456111 from Patent EP1572962. JD271024 - Sequence 252048 from Patent EP1572962. JD127215 - Sequence 108239 from Patent EP1572962. JD398345 - Sequence 379369 from Patent EP1572962. JD150162 - Sequence 131186 from Patent EP1572962. JD063666 - Sequence 44690 from Patent EP1572962. JD081809 - Sequence 62833 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P52945 (Reactome details) participates in the following event(s):
R-HSA-210747 Regulation of gene expression in early pancreatic precursor cells R-HSA-210745 Regulation of gene expression in beta cells R-HSA-186712 Regulation of beta-cell development R-HSA-1266738 Developmental Biology
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
