PDX1

Domain

The Antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter.

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).

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.

Involvement in disease

Pancreatic agenesis 1

PAGEN1

A disease characterized by isolated hypoplasia or agenesis of the pancreas, pancreatic beta-cell failure resulting in neonatal insulin-dependent diabetes mellitus, and exocrine pancreatic insufficiency.

None

The disease is caused by variants affecting the gene represented in this entry.

Diabetes mellitus, non-insulin-dependent

NIDDM

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.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Maturity-onset diabetes of the young 4

MODY4

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylated by the SAPK2 pathway at high intracellular glucose concentration. Phosphorylated by HIPK2 on Ser-268 upon glucose accumulation. This phosphorylation mediates subnuclear localization shifting. Phosphorylation by PASK may lead to translocation into the cytosol (By similarity).

Sequence similarities

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

Tissue specificity

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

Cellular localization

• Nucleus
• Cytoplasm
• Cytosol

Alternative names

• Pancreas/duodenum homeobox protein 1
• PDX-1
• Glucose-sensitive factor
• Insulin promoter factor 1
• Insulin upstream factor 1
• Islet/duodenum homeobox-1
• Somatostatin-transactivating factor 1
• GSF
• IPF-1
• IUF-1
• IDX-1
• STF-1
• PDX1
• IPF1
• STF1

Database links

• entrezGene:3651
• omim:600733
• swissprot:P52945

Target type

Proteins

Molecular weight

30771Da