FunctionActivates 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.
Tissue specificityDuodenum and pancreas (Langerhans islet beta cells and small subsets of endocrine non-beta-cells, at low levels in acinar cells).
Involvement in diseaseDefects 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. 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. 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.
Sequence similaritiesBelongs to the Antp homeobox family. IPF1/XlHbox-8 subfamily. Contains 1 homeobox DNA-binding domain.
DomainThe 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).
Post-translational modificationsPhosphorylated by the SAPK2 pathway at high intracellular glucose concentration.
Wang Q et al. The reprogrammed pancreatic progenitor-like intermediate state of hepatic cells is more susceptible to pancreatic beta cell differentiation. J Cell Sci126:3638-48 (2013).
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