Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Pdx1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2. The encoded nuclear protein is involved in the early development of the pancreas and plays a major role in glucose-dependent regulation of insulin gene expression. Defects in this gene are a cause of pancreatic agenesis, which can lead to early-onset insulin-dependent diabetes mellitus (NIDDM), as well as maturity onset diabetes of the young type 4 (MODY4). [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Pdx1
  • participates in the following biological processes:
    • glucose metabolic process ^[14]
    • negative regulation of transcription from RNA polymerase II promoter ^[4]
    • positive regulation of transcription from RNA polymerase II promoter ^{[7, 10]}
    • positive regulation of transcription, DNA-dependent ^[11]
    • regulation of cell proliferation ^[12]
    • regulation of transcription from RNA polymerase II promoter ^[7]
  • performs the following molecular functions:
    • chromatin binding ^[17]
    • DNA binding ^{[2, 4, 10, 11]}
    • sequence-specific DNA binding ^[7]
    • sequence-specific DNA binding transcription factor activity ^[10]
  • is located in the following cellular components:
    • intracellular part ^{[3, 9]}
    • nucleus ^{[6, 10, 12, 13, 16]}
• The gene product of Pdx1 has been shown to bind to the gene products of Meis1. ^[4]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Pdx1
  • participates in the following biological processes:
    • cell differentiation ^[5]
    • digestive tract development ^[15]
    • endocrine pancreas development ^[6]
    • exocrine pancreas development ^[8]
    • glucose homeostasis ^[6]
    • liver development ^[15]
    • morphogenesis of embryonic epithelium ^[1]
    • negative regulation of cell proliferation ^[6]
    • pancreas development ^{[1, 5]}
    • positive regulation of cell proliferation ^[6]
    • regulation of transcription from RNA polymerase II promoter ^[2]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Pdx1:
  • participates in the following biological processes:
    • cell differentiation
    • detection of glucose
    • glucose homeostasis
    • insulin secretion
    • negative regulation of transcription, DNA-dependent
    • nitric oxide mediated signal transduction
    • positive regulation of cell death
    • positive regulation of cell proliferation
    • positive regulation of DNA binding
    • positive regulation of insulin secretion
    • positive regulation of transcription from RNA polymerase II promoter
    • positive regulation of transcription, DNA-dependent
    • response to glucose stimulus
    • smoothened signaling pathway
    • stem cell differentiation
    • transcription from RNA polymerase II promoter
    • transcription, DNA-dependent
    • type B pancreatic cell differentiation
  • performs the following molecular functions:
    • core promoter sequence-specific DNA binding
    • protein complex binding
    • protein heterodimerization activity
    • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity
    • sequence-specific DNA binding
    • sequence-specific DNA binding transcription factor activity
    • transcription factor binding
  • is located in the following cellular components:
    • cytoplasm
    • nucleus

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Summary text based on GO annotations supported by structural data

• Pdx1 encodes a protein or proteins that contain the following InterPro domains: Homeobox protein, antennapedia type, Homeobox, conserved site, Homeodomain, Homeodomain, metazoa, Homeodomain-like, indicating that the gene product:
  • participates in the following biological processes:
    • regulation of transcription, DNA-dependent

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Pdx1 indicates that it:
  • participates in the following biological processes:
    • multicellular organismal development
    • regulation of transcription, DNA-dependent

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References

1. Ahlgren U et al. (1996) The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/ PDX1-deficient mice. Development, 122:1409-1416. (PubMed:8625829)
2. Annicotte JS et al. (2003) Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development. Mol Cell Biol, 23:6713-24. (PubMed:12972592)
3. Chu K et al. (2005) Neuronatin, a downstream target of BETA2/NeuroD1 in the pancreas, is involved in glucose-mediated insulin secretion. Diabetes, 54:1064-73. (PubMed:15793245)
4. Deramaudt TB et al. (2006) The PDX1 homeodomain transcription factor negatively regulates the pancreatic ductal cell-specific keratin 19 promoter. J Biol Chem, 281:38385-95. (PubMed:17056599)
5. Fujitani Y et al. (2006) Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev, 20:253-66. (PubMed:16418487)
6. Gannon M et al. (2008) pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol, 314:406-17. (PubMed:18155690)
7. Gerrish K et al. (2004) Conserved transcriptional regulatory domains of the pdx-1 gene. Mol Endocrinol, 18:533-48. (PubMed:14701942)
8. Hale MA et al. (2005) The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas. Dev Biol, 286:225-37. (PubMed:16126192)
9. Jensen J et al. (2000) Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation. Diabetes, 49:163-76. (PubMed:10868931)
10. Jepeal LI et al. (2005) Cell-specific expression of glucose-dependent-insulinotropic polypeptide is regulated by the transcription factor PDX-1. Endocrinology, 146:383-91. (PubMed:15486225)
11. Kataoka K et al. (2002) MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene. J Biol Chem, 277:49903-10. (PubMed:12368292)
12. Kitamura T et al. (2002) The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest, 110:1839-47. (PubMed:12488434)
13. Rosanas-Urgell A et al. (2005) Pdx1-related homeodomain transcription factors are distinctly expressed in mouse adult pancreatic islets. Mol Cell Endocrinol, 237:59-66. (PubMed:15888377)
14. Schubert M et al. (2003) Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci, 23:7084-92. (PubMed:12904469)
15. Spence JR et al. (2009) Sox17 regulates organ lineage segregation of ventral foregut progenitor cells. Dev Cell, 17:62-74. (PubMed:19619492)
16. Sumazaki R et al. (2004) Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Nat Genet, 36:83-7. (PubMed:14702043)
17. Ueda T et al. (2009) The nucleosome binding protein HMGN3 modulates the transcription profile of pancreatic beta cells and affects insulin secretion. Mol Cell Biol, 29:5264-76. (PubMed:19651901)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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