PDX1 Antibody – Rabbit Polyclonal

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]

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. 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.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.9Diabetes 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.