Disease:Defects in PDX1 are a cause of pancreatic agenesis [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. ,Disease:Defects in PDX1 are the cause of maturity onset diabetes noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type II. ,Disease:Defects in PDX1 are the cause of maturity onset diabetes of the young type 4 (MODY4) [MIM:606392]; also symbolized MODY-4. MODY [MIM:606391] is a form of diabetes mellitus characterized by an autosomal dominant mode of inheritance , age of onset of 25 years or younger and a primary defect in insulin secretion. ,Domain:The Antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter. ,Domain: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. 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. ,miscellaneous:According to PubMed:16141209 , it may be methylated by SETD7 in vitro. However , the relevance of methylation is unsure in vivo. ,PTM:Phosphorylated by the SAPK2 pathway at high intracellular glucose concentration. ,similarity:Belongs to the Antp homeobox family. IPF1/XlHbox-8 subfamily. ,similarity:Contains 1 homeobox DNA-binding domain. ,subunit: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. ,tissue specificity:Duodenum and pancreas (Langerhans islet beta cells and small subsets of endocrine non-beta-cells , at low levels in acinar cells) . ,
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