pancreas/duodenum homeobox protein 1; PDX-1; insulin promoter factor 1; IPF-1; Islet/duodenum homeobox-1; IDX-1; somatostatin-transactivating factor 1; STF-1; insulin upstream factor 1; IUF-1; glucose-sensitive factor; GSF (PDX1, IPF1)

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Function

activates insulin, somatostatin, glucokinase, islet amyloid polypeptide & glucose transporter type 2 gene transcription
especially involved in glucose-dependent regulation of insulin gene transcription
binds preferentially the DNA motif 5'-[CT]TAAT[TG]-3'
during development, specifies early pancreatic epithelium, permitting its proliferation, branching & subsequent differentiation
at adult stage, required for maintaining the hormone- producing phenotype of the beta-cell
phosphorylated by the SAPK2 pathway at high intracellular glucose concentration
interacts with the basic helix-loop-helix domains of TCF3(E47) & NEUROD1 & with HMG-I(Y)
interacts with SPOP
interacts with the methyltransferase SETD7

the antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter
the homeodomain contains the nuclear localization signal
- mediates DNA-binding
- acts as a protein-protein interaction domain for TCF3(E47), NEUROD1 & HMG-I(Y)
belongs to the antp homeobox family, IPF1/XlHbox-8 subfamily
contains 1 homeobox DNA-binding domain

expressed in duodenum & pancreas (Langerhans islet beta cells & small subsets of endocrine non-beta-cells, at low levels in acinar cells)

defects in PDX1 are a cause of
- pancreatic agenesis
- diabetes mellitus type-2
defects in PDX1 are the cause of maturity-onset diabetes of the young type 4 (MODY4)