Image:Schematic representation of functional domains and phosphorylation sites of PDX-1.jpg

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Figure 1. Schematic representation of functional domains and phosphorylation sites of PDX-1. The numbers indicate the positions of phosphorylation sites and functional domains on the polypeptide chain of human PDX-1. NLS: Nuclear localization signal; PTD: Protein transduction domain; S: Serine; T: Threonine. [1]


Human PDX-1 is a protein of 283 amino acids with a calculated molecular weight of 30.64 kDa. However, endogenous PDX-1 is usually detected as a protein with molecular mass of 46 kDa, likely due to posttranslational modifications such as phosphorylation and sumoylation. The N-terminus of PDX-1 contains a transactivation domain. The middle region contains a homeodomain, which is essential for DNA binding and protein-protein interactions. Within the homeodomain, there is an antennapedia-like protein transduction domain (PTD) which allows PDX-1 to permeate into cells and a nuclear localization signal (NLS) motif, RRMKWKK(197-203aa), which is sufficient for the nuclear import of PDX-1. There is a conserved motif in the C-terminus of PDX-1 that mediates the PDX-1-PCIF1 interaction resulting in the inhibition of PDX-1 transcriptional activity. Several C-terminal residues such as Gly 212, Glu 224 and Pro 239 are essential for full transactivation of PDX-1 as evidenced by the association of their missense mutations with diabetes (Fig. 2). Several potential phosphorylation sites within PDX-1 have been identified, such as Thr 11 by DNA-PK, Ser 61 and 66 by GSK3beta, Thr 152 by PASK, Thr 231 and Ser 232 by CK2 and Ser 268 by AKT-GSK and HIPK2.



References

  1. http://atlasgeneticsoncology.org/Genes/PDX1ID43921ch13q12.html

Links

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(current)08:42, 28 December 2013Megane Denu (Talk | contribs)725×15831 KBFigure 1. Schematic representation of functional domains and phosphorylation sites of PDX-1. The numbers indicate the positions of phosphorylation sites and functional domains on the polypeptide chain of human PDX-1. Human PDX-1 is a protein of 283 ami

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